bluuebunny/crossref_metadata_2025 huggingface dataset:
SURG-03. SURGICAL MANAGEMENT OF BRAIN METASTASIS FROM OVARIAN CANCER: A SYSTEMATIC REVIEW AND CASE SERIES
Authors: Costello Meredith , Bashti Malek , Merenzon Martin , Morell Alexis , Patel Nitesh , Higgins Dominique , Kader Michael , Shah Ashish , Eichberg Daniel , Luther Evan , Komotar Ricardo , Ivan Michael
Published: November 2022

INTRODUCTION

Ovarian cancer is a rare cause of brain metastasis requiring neurosurgical intervention. Management strategies vary and prognostic factors are not well known.

OBJECTIVE

We aim to systematically review the literature on management and outcomes of ovarian cancer brain metastasis and compare it with our experience.

METHODS

Systematic review was performed using PRISMA guidelines. Databases were sourced from inception to April 2022. Study selection was based on predetermined inclusion/exclusion criteria. A simultaneous retrospective analysis was performed on patients from our institution who underwent evaluation and treatment for metastatic intracranial lesions of ovarian origin.

RESULTS

Literature search generated 214 articles. Twelve were ultimately selected, representing 428 brain metastasis (BM) patients from ovarian cancer. Patients age from 27-80 years. The interval from cancer diagnosis to BM ranged from 0 – 226.2 months. Surgical resection (SR), stereotactic radiosurgery (SRS), and whole-brain radiotherapy were the most frequently used treatment modalities. Individual patients’ overall survival following BM diagnosis ranged from 0 – 173 months. For our institutional analysis, 9 patients were included with median age of 56 years. Median interval from diagnosis to BM was 51 months. Four patients were treated with SR and adjuvant SRS. Two patients had SR and SRS with additional extraventricular drain placement. Two patients had SR only, and one received only SRS. Median radiation dose received was 20 Gy. For those who experienced progression, median progression-free survival was 14 months. One patient exhibited no progression at the time of analysis. Three patients were alive at the time of analysis with two others lost to follow-up.

CONCLUSION

brain metastases following ovarian cancer are a rare outcome carrying a poor prognosis. Multimodal therapies, specifically SR and SRS, correlate with increased survival. Further study is needed to better guide optimal management, with particular attention to the benefits of resection with targeted adjuvant radiation.
SURG-04. CDK2NA/B, SMAD4, AND PIK3R1 MUTATIONS ARE ASSOCIATED WITH INCREASED RISK OF LOCAL RECURRENCE AFTER SURGICAL RESECTION OF BRAIN METASTASES
Authors: Morshed Ramin A , Cummins Daniel , Nguyen Minh , Young Jacob S , Theodospoulos Philip , Hervey-Jumper Shawn L , Aghi Manish , Daras Mariza
Published: November 2022

BACKGROUND

While resection of brain metastases (BMs) offers favorable local disease control, factors and genetic alterations associated with local recurrence are not well defined. This study examined patient, tumor, treatment, and genetic factors associated with local recurrence.

METHODS

A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical outcome and genetic data available. Local recurrence was the primary outcome of the study. Next-generation sequencing of coding regions in over 500 cancer genes was performed to detect mutations. Cox proportional hazards analysis was performed to identify patient, tumor, treatment, and genetic factors associated with local recurrence.

RESULTS

We identified 91 patients who underwent surgical resection of a BM with available data, of which 80 (87.1%) underwent preoperative radiotherapy or received some form of adjuvant radiation to the resection cavity. Primary pathologies in the cohort included non-small cell lung cancer (24.2%), melanoma (24.2%), breast cancer (16.5%), gastrointestinal cancers (13.2%), gynecologic cancers (4.4%), renal cell carcinoma (4.4%), and other cancers (13.2%). Eleven patients (12.1%) developed postoperative recurrence at the surgical site with 6- and 12-month PFS of 91.2% and 84.2%. Multivariate Cox proportional hazard analysis identified cancer type (Gyn and RCC vs Others: OR 39.4, p=0.002), CDK2NA/B co-deletion (OR 37.52, p=0.0009), PIK3R1 mutation (OR 56.88, p=0.003), and SMAD4 mutation (OR 134.8, p=0.0007) to be associated with time to local recurrence. Overall survival and length of follow-up were not different based on mutational status of these genes, demonstrating that results were not due to survival bias.

CONCLUSIONS

Genetic alterations within BMs impact clinical outcomes after surgical resection. Further work is needed to determine if targeted therapies for BMs with these alterations can decrease rates of local recurrence.
SURG-05. SUPERVISED MACHINE LEARNING IDENTIFIES RISK FACTORS ASSOCIATED WITH LEPTOMENINGEAL DISEASE AFTER SURGICAL RESECTION OF BRAIN METASTASES
Authors: Morshed Ramin A , Saggi Satvir , Cummins Daniel , Young Jacob S , Viner Jennifer , Villanueva-Meyer Javier , Goldschmidt Ezequiel , Boreta Lauren , Braunstein Steve , Chang Edward , McDermott Michael , Berger Mitchel S , Theodospoulos Philip , Hervey-Jumper Shawn L , Aghi Manish , Daras Mariza
Published: November 2022

INTRODUCTION

Predictors of postoperative leptomeningeal disease (LMD) after resection of brain metastases (BMs) are not well defined.

OBJECTIVE

This study examined rates and predictors of LMD, including subtypes, in patients who underwent resection of a BM followed by postoperative radiation.Method: A retrospective, single-center study was conducted examining overall LMD, classical LMD (cLMD), and nodular LMD (nLMD) risk. Logistic regression and a Cox proportional hazards analyses were performed to identify risk factors associated with LMD. Random forest models were constructed to predict LMD and differentiate cLMD versus nLMD. Accuracy and the area under the receiver operating characteristic curve (AUROC) were calculated to evaluate the models.Result: Of the 217 patients in the cohort, 47 (21.7%) developed postoperative LMD with 19(8.8%) cLMD cases and 28(12.9%) nLMD cases . Six-, 12-, and 24-month LMD-free survival rates were 92.3%, 85.6%, and 71.4%, respectively. Patients with cLMD had worse survival outcomes from LMD diagnosis compared to nLMD (2.4 vs 6.9 mo, Log-rank p=0.02), and treatment of LMD was associated with improved survival for both cLMD and nLMD subtypes. Multivariate Cox hazard analysis identified cerebellar/insular/occipital location (HR 3.25, 95% CI 1.73-6.11, p=0.0003), absence of extracranial disease (HR 2.49, 95% CI 1.27-4.88, p=0.008), and ventricle contact (HR 2.82, 95% CI 1.5-5.3, p=0.001) to be associated with postoperative LMD. A predictive model using random forest analysis with an AUROC of 0.87 in a test cohort identified tumor location, systemic disease status, and tumor volume as the most important factors associated with LMD. Both regression analysis and random forest analysis identified postoperative systemic therapy exposure as the main factor differentiating cLMD from nLMD development.

CONCLUSION

Tumor location, absence of extracranial disease at the time of surgery, contact with a ventricle, and increased tumor volume are associated with LMD. Classical LMD is associated with worse prognosis compared to nLMD.
SURG-07. SURGICALLY TREATED BRAIN METASTASES FROM UTERINE ORIGIN: A CASE SERIES AND SYSTEMATIC REVIEW
Authors: Eatz Tiffany , Levy Adam , Bystrom Laure , Morell Alexis , Merenzon Martin , Higgins Dominique , Eichberg Daniel , Kader Michael , Guyot Manuela , Schlumbrecht Matthew , Patel Nitesh , Shah Ashish , Silva Michael , Komotar Ricardo , Ivan Michael
Published: November 2022

INTRODUCTION

Brain metastases from uterine origin have an incidence of 0.7-1.1%. Due to their rarity, there exists scarce literature entailing their neurosurgical treatment and outcomes.

OBJECTIVE

To report case management and outcomes of nine patients with brain metastases from uterine origin, as well as a systematic literature review findings focused on their neurosurgical treatment and outcomes.

METHODS

This study was divided into two parts: (1) a retrospective, single-center patient series assessing neurosurgical outcomes in patients with primary uterine cancer with brain metastases and (2) a systematic review of the literature between 1980 and 2021 assessing outcomes of patients with primary uterine cancer metastasized to the brain.

RESULTS

We report a case series at our single institution consisting of nine patients identified to have metastases to the brain from uterine origin that were treated with neurosurgical intervention. A total of 26 CNS lesions were identified among the 9 cases, with a mean number of lesions of 2.9 (1-7). The median age at the time of primary uterine cancer diagnosis was 49 years (26-80 years), with a median time from diagnosis to CNS metastasis of 19.5 months (3-54 months). The most common cerebral regions affected were the frontal lobe (42.3%) and the cerebellum (23%). Median progression free survival (PFS) and overall survival (OS) following intervention were 6.5 and 17.4 months, respectively. Stereotactic radiosurgery (SRS) alone resulted in the highest PFS and OS of 20.3 and 39 months, respectively. Sixteen studies were included in the systematic analysis. The mean OS was 13.3 months (3-41.1 months).

CONCLUSION

Brain metastases from uterine origin seem to most frequently result in multiple symptomatic lesions with additional concurrent metastasis to other organs. The most effective treatment modality appeared to be SRS alone. There is limited data on sole SRS treatment, so additional research regarding this modality is encouraged.
SURG-08. COMBINED LOCAL TREATMENT OF BRAIN METASTASES: SURGERY AND POSTOPERATIVE STEREOTACTIC RADIOTHERAPY
Authors: Fadrus Pavel , Vybihal Vaclav , Juran Vilem , Roskova Ivana , Sprlakova-Pukova Andrea , Koprivova Tereza , Kerkovsky Milos , Lakomy Radek , Kazda Tomas , Hynkova Ludmila , Belanova Renata , Vecera Marek , Hermanova Marketa , Jancalek Radim , Sana Jiri , Slaby Ondrej , Slampa Pavel , Smrcka Martin
Published: November 2022

INTRODUCTION

Modern comprehensive local treatment of BM provides the possibility of adequate local control while maintaining a satisfactory quality of life.

METHODS

Patients after metastasectomy and postoperative radiotherapy treated between 2007-2020 were evaluated. Local control was assessed separately at the site of the operated MM (localPFS) and separately in other parts of the brain (distalPFS).

RESULTS

A total of 118 patients were enrolled (70 with WBRT), 54% were women, the median age was 60 years, the median performance status Karnofsky 80%. The most common primary tumor was lung carcinoma (39/118, 33%). Targeted stereotactic radiotherapy was significantly more often indicated in operations performed after 2016 (p < 0.001). In the period 2013-2019, gross total resection was achieved significantly more often (83 vs 64%; p = 0.061). The median follow-up is 49 months. The median overall survival (OS) is 9 months (6.2 - 12), the median localPFS 22 months (14 - unattainable), median distPFS 11 months (6.8 - 27 months), median extracranialPFS 11 months (5.9 - 15). Stratification of patients according to the prognostic index brainmetgpa.com led to significant separation of patients for OS (p = 0.00017). In a multivariate analysis, stereotactic radiotherapy was statistically significant positive prognostic factor for OS compared to WBRT (median OS 17 vs. 5.6 months, HR 0.59, p = 0.018) with no effect on localPFS.

CONCLUSION

Our results of comprehensive local treatment of BM are comparable with the results presented by important foreign studies from prestigious oncology centers. We described targeted stereotactic postoperative radiotherapy as an independent positive prognostic factor after brain metastasectomy. The study was supported by the programme project of the Ministry of Health of the Czech Republic with reg. no. NV18-03-00398, NV19-03-00501 and NV19-03-00559 and Supported by Ministry of Health, Czech Republic-conceptual development of research organization (FNBr, 65269705).
SURG-09. EFFICACY OF A BIWEEKLY 3-STAGE STEREOTACTIC RADIOSURGERY FOR LARGE BRAIN METASTASES: THE EFFECT OF EGFR TYROSINE-KINASE INHIBITOR ON TUMOR RESPONSE AND CLINICAL OUTCOMES
Authors: Kwon Ji-Eyon , Park Hyun Joo , Ji So Young , Han Jung Ho , Hong Yong-Kil , Kim Chae-Yong
Published: November 2022

Stereotactic radiosurgery(SRS) is one of primary treatment modalities for brain metastases(BM), however local control and radiation necrosis of large BM remain challenging. To overcome these limitations, biweekly 3-stage SRS for LBM was performed in this study. Total 53 patients were treated for 62 LBM. Female was 27(50.9%), and mean age was 63.7±11.8years. The mean KPS was 79.2±9.0 and GPA score was 1.9±0.7. Non-small cell lung cancer(NSCLC) was the most common primary cancer in 31 patients, others include 6 small cell lung cancer(SCLC), 9 gastro-intestinal tract cancer, 5 gynecological cancer, and etc. Epidermal growth factor receptor(EGFR) mutation was identified in 13 patients, and EGFR tyrosine-kinase inhibitor(TKI) was used in 10 patients during and after staged SRS. The mean tumor volume was 19.1cm3. The mean marginal dose of 11.7Gy was delivered to the 50% isodose line based on new treatment planning every two weeks. The mean tumor volume at the second and third stage was 14.8cm3 and 11.0cm3, respectively. The lesions from squamous cell carcinoma of NSCLC decreased most rapidly, and followed by gynecological cancer, SCLC and adenocarcinoma of NSCLC(volume ratio at 3rd stage was 0.39, 0.53, 0.56, and 0.64, respectively). The most significant factor related with tumor volume reduction at 3rd stage was usage of EGFR-TKI(p=0.016; LR analysis). The mean overall survival(OS) was 15.3months, and estimated OS were 62% and 46% at 6 and 12months. In the multivariate analysis, KPS(OR=0.918; 95% CI,0.871-0.968; p=0.002) and usage of EGFR-TKI(OR=0.216; 95% CI,0.059-0.790; p=0.021) were significantly associated with OS. The mean OS of the group of usage of EGFR-TKI was significantly longer than that of the others(20.7months, and 13.1months; p=0.029; log-rank test). The biweekly 3-stage SRS seems to be effective treatment for patients with LBM, especially in patients who were treated with EGFR-TKI during and/or after SRS, also cautiously considering the primary tumor origin.
SURG-12. SURGICAL INTERVENTION FOR PRIMARY B-CELL LYMPHOMA OF THE SPINE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF CLINICAL PRESENTATION, HISTOLOGICAL MARKERS, TREATMENTS, AND SURVIVAL OUTCOMES
Authors: Gendreau Julian , Patel Neal , Brown Nolan , Lee Seung Jin , Chan Andrew , Sahyouni Ronald
Published: November 2022

B-cell lymphoma is a potential cause of spinal cord compression that presents with nonspecific symptoms and inconsistent imaging findings. Surgical decompression is a mainstay for both diagnosis and management especially in patients with acute neurologic deficits; however, the long-term efficacy of intervention is still unclear. We perform a systematic review of the clinical symptoms, radiographic findings, and outcome after spinal decompression in B-cell lymphoma. The databases of Medline, PubMed, and the Cochrane Database of Systemic Reviews were queried for all articles reporting spinal B-cell lymphoma. Data on presenting symptoms, histological markers, treatment and survival outcomes were extracted. Bivariate and Multivariate Cox survival regression models and Kaplan-Meier curves were generated using R software survival package. In total, 57 studies were included with 72 patients diagnosed with spinal B-cell lymphoma. Mean age was 56.22 (IQR: 45.00-70.25) with 68% of patients being male and 4.2% of patients being immunocompromised. Back pain was the most common symptom (74%) with B symptoms and cauda equina symptoms present in only 6% and 29% respectively. Mean length of symptoms before presentation was 3.81 months (IQR: 0.45-3.25). The most common location was the thoracic spine (53%), with a majority of the lesions being hyperintense (28%) on T2 MRI. Surgical resection was performed in 83% of patients. Symptoms improved in 88% of patients after surgery and 80% of patients treated nonoperatively. OS at one- and five-years was 85% (95% CI: 0.749-0.953; n=72) and 66% (95% CI: 0.512-0.847; n=72), respectively. Age > 70 was associated with poorer OS in bivariate (HR 4.07 [95% CI: 1.328-12.46], p < 0.01; n=72) and multivariate analysis (HR 3.829 [95% CI: 1.158-12.662], p < 0.03; n=72). Primary spinal B-cell lymphoma can have a variety of presentations. Both surgery and nonoperative management may have similar improvement in symptoms. Age > 70 appears to confer poorer OS.
SURG-13. SYSTEMATIC REVIEW AND META-ANALYSIS OF IMPACT OF EXTENT OF RESECTION ON SURVIVAL ON GLIOBLASTOMA, IDH-WILDTYPE, WHO GRADE 4 (WHO 2021)
Authors: Jusue-Torres Ignacio , Lee Jonathan , Germanwala Anand , Burns Terry , Parney Ian
Published: November 2022

BACKGROUND

Glioblastoma diagnostic criteria have been redefined with the 5th edition of WHO classification of tumors of the central nervous system. Glioblastomas are defined as IDH wildtype diffuse astrocytic glioma tumors with one of the following features: microvascular proliferation, or necrosis, or TERT promoter mutation, or EGFR gene amplification, or +7/-10 chromosome copy number changes. The aim of this study is to establish the impact of extent of resection in overall survival (OS) and progression free survival (PFS) in glioblastoma, IDH-wildtype (WT), WHO grade 4 (WHO 2021).

METHODS

Systematic literature search was performed using the following databases: PubMed, Web of Science, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and ClinicalTrials.gov to identify studies comparing OS and PFS after gross total resection (GTR) vs subtotal resection (STR) or biopsy for glioblastoma IDH-WT. Prognostic hazard ratios (HR) for OS and PFS were analyzed using a random-effects model.

RESULTS

We identified 1439 publications. Nine studies met inclusion/exclusion criteria. 788 patients underwent GTR out of 1818. The meta-analysis showed a significant increase in OS and PFS duration when undergoing GTR for glioblastoma IDH-WT with a median OS of 20 months 95% CI (17-25) compared to 12 months 95% CI (9-15) for STR or biopsy and a median PFS of 11 months 95% CI (9-12) for GTR compared to 7 months 95% CI (5-7) for STR or biopsy respectively. GTR showed a 49% significant reduction of mortality risk HR=0.51 95%CI (0.42-0.59) and a 44% significant reduction of progression risk HR=0.56 95%CI (0.41-0.71) compared to STR or biopsy.

CONCLUSIONS

This systematic review indicates that GTR may be associated with improved OS and PFS compared to STR or biopsy for Glioblastoma, IDH-WT, WHO grade 4 (WHO 2021). However, this is limited by variable study design and significant clinical and methodological heterogeneity among studies.
SURG-14. LOWER-GRADE GLIOMA IN ELDERLY PATIENTS: TREATMENT AND OUTCOMES IN A MOLECULARLY CHARACTERIZED CONTEMPORARY COHORT
Authors: Jungk Christine , Gluszak Mara , Trong Philip Dao , von Deimling Andreas , Herold-Mende Christel , Andreas Unterberg
Published: November 2022

Lower-grade glioma (LGG) is rare among patients above the age of 60. Previous series reported poor outcomes, likely due to a high proportion of missed IDH wildtype astrocytomas which today would be diagnosed as glioblastoma, and thus proposed defensive treatment in elderly patients. We questioned these findings in our contemporary cohort of “true” LGGs, i.e. IDH mutant astrocytoma and oligodendroglioma WHO grade 2 and 3. Patients aged 60 years and older (“elderly”) treated for hemispheric LGG were retrospectively analyzed for demographic, tumor- and treatment-related factors and progression-free survival (PFS) and were compared to a cohort of patients younger than 60 years. Inclusion criteria, amongst others, were availability of molecular data and volumetric assessment of pre- and postoperative tumor burden. 212 patients were analyzed, among those 21 elderlies (9.9%). Elderly patients did not differ from younger ones regarding preoperative tumor volumes, eloquent location, presence of contrast enhancement and clinical presentation (seizures, focal deficits). In both groups (elderly vs. younger), most patients underwent tumor resection (81% vs. 90.6%; p=0.25) with comparable median residual tumor volumes (5.12 cm3 vs. 3.28 cm3; p=0.66). There was a trend towards more aggressive surgical approaches in younger patients, e.g., use of IOM and awake surgery. However, rates of functional deterioration (p=0.2) and revision surgery (p=0.98) were comparable. Oligodendroglioma, in relation to astrocytoma, was more common in the elderly (76.2% vs. 46.1%; p=0.011). Adjuvant radio- and/or chemotherapy was administered in 76.2% of elderly and 59.8% of younger patients (p=0.163). Median PFS was comparable (50 vs. 56 months; p=0.62), regardless of WHO grade (p=0.43) and tumor subtype (p=0.93). In conclusion, favorable surgical and survival outcomes were achieved in our series that were comparable to those of younger patients. Thus, intensified treatment including maximal safe resection should be advocated in elderly patients whenever feasible.
SURG-17. PROGNOSIS IN IDH-MUTANT GLIOMA: THE ROLE OF EXTENT-OF-RESECTION, AGE AND TUMOR GRADE
Authors: van der Vaart Thijs , van Garderen Karin , Wijnenga Maarten , Dubbink Erik Jan , French Pim , Smits Marion , Dirven Clemens M F , Kros Johan , Vincent Arnaud , van den Bent Martin
Published: November 2022

BACKGROUND

Evidence suggests that smaller residual tumor volumes after initial surgery are associated with longer survival in patients with astrocytoma, IDH-mutant, grade II. For IDH-mutant glioma of higher grade but also for oligodendroglioma, IDH-mutant, and 1p/19q codeleted, the impact of residual tumor volume on survival is unclear. This could be related to the limited follow-up of patients with oligodendroglioma that typically have long overall survival. We expanded a previously published series of patients increase the duration of follow-up and the spectrum of tumor grades.

METHODS

Single center observational cohort study of patients with adult-type diffuse glioma, IDH-mutant, all WHO-2021 grades, from 2003 to 2021 . Molecular characteristics were assessed by next-generation targeted sequencing. Tumor volumes were calculated by semi-automatic 3D segmentation on pre- and postoperative MRI-scans. Associations between prognostic factors and survival were assessed using univariate and multivariate Cox proportional hazards models.

RESULTS

384 patients with IDH-mutant glioma (174 oligodendroglioma, 212 astrocytoma) were followed for a median of 7 years. Median age at diagnosis was 41 years (IQR 33 – 55). Significant prognostic factors for survival were Karnofsky performance status, 1p19q-status and post-operative tumor volume. Smaller post-operative tumor volume was associated with better survival, both in astrocytoma and oligodendroglioma. Age, tumor grade and MRI-contrast enhancement were not associated with survival.

CONCLUSION

Lower residual tumor volume after first surgery is a strong prognostic factor in all IDH-mutant glioma subgroups, even in patients with very small residual tumor. Importantly, age and histological tumor grade were not significantly associated with survival. The data serves as further support for optimal initial resections of tumors suspected for IDH-mutant glioma, also in oligodendroglioma.
SURG-21. DEVELOPMENT OF MICROSURGICAL FORCEPS EQUIPPED WITH HAPTICS TECHNOLOGY FOR IN SITU DIFFERENTIATION OF TUMOR TISSUE FROM NORMAL BRAIN DURING MICROSURGERY BY TISSUE STIFFNESS
Authors: Ezaki Taketo , Kishima Kohki , Pareira Eriel , Shibao Shunsuke , Matsunaga Takuya , Kitamura Yohei , Takahara Kento , Sampetrean Oltea , Ohnishi Kouhei , Toda Masahiro , Shimono Tomoyuki , Sasaki Hikaru
Published: November 2022

Neurosurgeons perform tumor resection based on their tactile perception. However, many years of experience and training are required to appropriately differentiate tumor tissue from surrounding parenchymal tissue. It was reported that the stiffness of human cancer tissue strongly correlates with pathological tissue and it can be used as a biomarker. Comprehensive analysis also revealed that the molecular expression differs greatly between hard and soft tumors.Haptics technology measures and uses the stimulus that causes the sensation as a physical quantity. Force and tactile sensation is a sensation caused by mechanical contact with an object. Real Haptics is our main research field, which is a general term for technologies that quantify and utilize the force-tactile stimuli generated by contact with objects that exist in the real world and / or the virtual world.We have developed a microsurgical forceps equipped with haptics technology to differentiate tumor tissue from surrounding brain tissue during tumor dissection. We generated and used three glioblastoma cell lines (SF126, U87, U251) expressing proteins of firefly luciferase and mCherry. Each cell line was transplanted into forebrain of 5 nude mice. Tumor progression was regularly monitored with In Vivo Imaging System (IVIS) and mice were euthanized at the appropriate stage. Tumor and normal brain stiffness were measured by using the Master-slave integrated haptic forceps device. Importantly, all of the three glioblastomas were shown to be harder than the normal brain (p=0.047). The median stiffness of each tissue was as follows. Normal brain (n=15): 149.98 N/m, SF126 (n=5): 207.70 N/m, U87 (n=5): 214.40 N/m, U251 (n=5): 188.86 N/mThis pilot study showed that brain tumors could be differentiated by their stiffness from normal brain, and the forceps equipped with haptics technology might help the neurosurgeons to dissect tumor margin along the appropriate plane.
SURG-30. SURGICAL MANAGEMENT OF A RARE SACROCOCCYGEAL MYXOPAPILLARY EPENDYMOMA OF THE GLUTEAL REGION: CASE ILLUSTRATION AND SYSTEMATIC LITERATURE REVIEW
Authors: Brown Nolan , Lien Brian , Himstead Alexander , Ball Benjamin , Hsu Frank
Published: November 2022

Ependymomas are rare tumors originating from neuroepithelial cells lining the wall of the ventricles or central canal of the spinal cord. While these tumors mainly occur within the central nervous system (CNS), there are occasional reports in children and young adult patients with a primary tumor occurrence outside of the CNS. Ependymomas of the sacrococcygeal region have been infrequently described in the literature with no standard of care established. We present a case report and review of the literature regarding this rare entity. A 24-year-old woman presented with right gluteal pain worsened by sitting and a palpable soft tissue mass of the sacrococcygeal region. Magnetic resonance imaging revealed a 3.7 cm cystic mass centered in the right gluteal region. Histology revealed myxopapillary ependymoma. The patient underwent an interdisciplinary neurosurgical and orthopedic oncology en bloc resection of the ependymoma, which intraoperatively appeared to originate from the coccygeal nerve. Through our systematic literature review, we identified 38 studies describing 78 unique cases of myxopapillary ependymoma occurring in the sacrococcygeal region without extension into the CNS. The exact presentation of sacrococcygeal ependymomas is variable. Given their location and propensity for drainage, they are frequently misdiagnosed as pilonidal cyst. Recurrence occured in 16.7% of cases described, typically within 20 years. Rate of metastasis was 20%. The primary means of management for sacrococcygeal myxopapillary ependymoma is complete surgical resection including excision of the neighboring sacrum or coccyx, when involved. Ultimately, we demonstrate that a myxopapillary ependymoma may present as an isolated gluteal mass attached to the coccygeal nerve, without frank CNS involvement. Furthermore, an interdisciplinary approach to surgical resection of this lesion appears to represent an effective treatment modality.
SURG-33. RATES OF PRE-OPERATIVE SEIZURE IN PATIENTS WITH MENINGIOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Nguyen Andrew , Brown Nolan , Nguyen Brandon , Harris Mark , Singh Rohin , Shahrestani Shane , Gendreau Julian , Mohyeldin Ahmed
Published: November 2022

Recent literature has primarily focused on the factors influencing postoperative seizures following resection of meningioma, but many patients also suffer seizures preoperatively. This meta-analysis examined patient demographics, tumor characteristics, and preoperative symptoms to determine which factors are most associated with preoperative seizures. A literature search of Pubmed, Web of Science, and Scopus was conducted. All randomized controlled trials, case-control studies, and cohort studies reporting on preoperative seizure in patients with meningioma were included for analysis. The initial search yielded 4129 total studies, 33 of which were included for quantitative analysis. A total of 8221 patients were analyzed and the rate of preoperative seizure was 26%. Patients were classified as adult vs pediatric and male vs female for analysis. Meningiomas were classified as midline/bilateral vs left-sided vs right-sided, WHO grade 1 vs grade 2-3, greater than 4 cm3 vs less than 4 cm3, and skull base vs non-skull base location. The preoperative signs and symptoms analyzed included presence of headaches, tumor-related edematous change, and neurological deficits. Preoperative seizures were more common in pediatric patients (p< .02) and males (p< .0001). Patients with tumors classified as midline (p< .0001), WHO grade 2-3 (p< .0001), larger than 4 cm3 (p< .0001), and skull base location (p< .0001) were more likely to experience preoperative seizures. Preoperative headaches (p< .0001) were less common in patients with preoperative seizures. Edematous change (p< .0001) and neurological deficits (P< .0001) were more common in patients with pre-operative seizures. On assessment of risk for study bias, no publication bias was detected. This meta-analysis displayed that over 20% of meningioma patients suffer from preoperative seizures. Notably, pediatric patients, patients with midline and skull base meningiomas, and males of all ages were more likely to experience preoperative seizure. Interestingly, patients with preoperative seizures were less likely to experience headaches.
High Mg# of the continental crust explained by calc-alkaline differentiation
Authors: Tang Ming , Liu Xuanyu , Chen Kang
Published: November 2022

We used compiled geochemical data to investigate the mechanisms that control Mg# (molar ratio of Mg/(Mg + FeT)) in andesitic arc lavas. We find that andesites from mature continental arcs with crustal thickness of >45 km have systematically higher Mg# than those from oceanic arcs with crustal thickness of <30 km. The elevated Mg# in continental arc lavas results from strong Fe depletion during high-pressure differentiation favored in thick crusts. This proposal is reinforced by our compiled melting/crystallization experiment data. We show that the Mg# characteristics of continental arc lavas match that of the continental crust. These findings suggest that the formation of many high-Mg# andesites and the continental crust may not require slab-melt/peridotite interactions. Instead, the high Mg# of the continental crust can be explained by intracrustal calc-alkaline differentiation processes in magmatic orogens.
Adoption and Trends in Uptake of Updated ICD-10 Codes for Clostridioides difficile—A Retrospective Observational Study
Authors: Deshpande Abhishek , Chen Yiyun , Boye-Codjoe Eugenia , Obi Engels N
Published: November 2022

Background

In October 2017, the single International Classification of Diseases, Tenth Revision (ICD-10), code for Clostridioides difficile infection (CDI), A04.7, was replaced with 2 codes delineating “recurrent CDI” (rCDI; A04.71) and “nonrecurrent CDI” (nrCDI; A04.72).

Methods

To evaluate and validate use of the updated codes, this retrospective study included inpatient encounters with a CDI-related ICD-10 code from October 2016 to May 2019 in the PINC AITM Healthcare Database (PHD). Encounters after the October 2017 code update were characterized by clinical, facility, and provider variables and whether coding was concordant or discordant to the 8-week recurrence period. Multivariable regression analysis assessed variables associated with concordant coding.

Results

Widespread adoption of the updated CDI codes across PHD hospitals occurred in October 2017. After October 2017, 21 446 CDI-related encounters met sample selection criteria (concordance in 67% of rCDI and 25% of nrCDI encounters). Higher proportions of rCDI- vs nrCDI-coded encounters (P < .05) had emergency room admission, admission by a gastroenterologist or infectious disease specialist, and were prescribed fidaxomicin, bezlotoxumab, or fecal microbiota transfer (FMT), with no significant difference by coding concordance status. Encounters coded concordantly were significantly more likely to be for rCDI (odds ratio [OR], 5.67; 95% CI, 5.32–6.03), a nonelective admission (OR, 1.35–1.69), or prescribed fidaxomicin (OR, 1.11; 95% CI, 1.01–1.23) or FMT (OR, 1.29; 95% CI, 1.17–1.42).

Conclusions

Our study findings suggest no delay in transition to the updated CDI-related codes. Treatment patterns for rCDI vs nrCDI encounters were consistent with Infectious Diseases Society of America guidelines, regardless of concordance status.
Novel idea generation in social networks is optimized by exposure to a “Goldilocks” level of idea-variability
Authors: Baten Raiyan Abdul , Aslin Richard N , Ghoshal Gourab , Hoque Ehsan
Published: November 2022

Recent works suggest that striking a balance between maximizing idea stimulation and minimizing idea redundancy can elevate novel idea generation performances in self-organizing social networks. We explore whether dispersing the visibility of high-performing idea generators can help achieve such a trade-off. We employ popularity signals (follower counts) of participants as an external source of variation in network structures, which we control across four conditions in a randomized setting. We observe that popularity signals influence inspiration-seeking ties, partly by biasing people’s perception of their peers’ novel idea-generation performances. Networks that partially disperse the top ideators’ visibility using this external signal show reduced idea redundancy and elevated idea-generation performances. However, extreme dispersal leads to inferior performances by narrowing the range of idea stimulation. Our work holds future-of-work implications for elevating idea generation performances of people.
A multivalent antibody assembled from different building blocks using tag/catcher systems: a case study
Authors: Schindler Christof , Faust Christine , Sjuts Hanno , Lange Christian , Kühn Jennifer , Dittrich Werner , Leuschner Wulf Dirk , Schiebler Werner , Hofmann Joachim , Rao Ercole , Langer Thomas
Published: November 2022

The field of therapeutic antibodies and, especially bi- or multispecific antibodies, is growing rapidly. Especially for treating cancers, multispecific antibodies are very promising, as there are multiple pathways involved and multispecific antibodies offer the possibility to interfere at two or more sites. Besides being used as therapeutic, multispecific antibodies can be helpful tools in basic research. However, the design and choice of the most appropriate multispecific antibody format are far from trivial. The generation of multispecific antibodies starts with the generation of antibodies directed against the desired targets and then combining the different antigen-binding sites in one molecule. This is a time-consuming and laborious approach since the most suitable geometry cannot be predicted. The SpyTag technology is based on a split-protein system, where a small peptide of said protein, the SpyTag, can bind to the remaining protein, the SpyCatcher. An irreversible isopeptide bond between the SpyTag and the SpyCatcher is formed. A related Tag-Catcher system is the SnoopTag-SnoopCatcher. These systems offer the opportunity to separately produce proteins fused to the tag-peptides and to the catcher-domains and assemble them in vitro. Our goal was to design and produce different antibody fragments, Fab domains and Fc-containing domains, with different tags and/or catchers as building blocks for the assembly of different multivalent antibodies. We have shown that large multivalent antibodies consisting of up to seven building blocks can be prepared. Binding experiments demonstrated that all binding sites in such a large molecule retained their accessibility to their corresponding antigens.
Mediating probate and trust disputes—process challenges and tools: part 1
Authors: Islam Carl
Published: November 2022

While it is not the function of a mediator to speak truth to power, a mediator can facilitate the re-framing of a dispute as an opportunity, by enabling each participant to think about what is important to them, so that the participants can jointly agree upon a ‘methodology’, i.e. a ‘road map’ for convergence and consensus. This requires a ‘paradigm shift’, i.e. acceptance by each participant that there is a better way of resolving their dispute than proceeding to trial. In Part 1, the author discusses the benefits of mediation, the process, ground rules, and how best to prepare for the mediation day. In Part 2 (to be written in 2023), the author will discuss the challenges throughout each phase of the mediation day, and the tools available to a mediator to help engineer a sudden outbreak of common sense in a probate and trust dispute.
Nasal nitric oxide flux from the paranasal sinuses
Authors: Spector Barak M. , Shusterman Dennis J. , Zhao Kai
Published: November 2022

Purpose of review

Upper airway nitric oxide (NO) is physiologically important in airway regulation and defense, and can be modulated by various airway inflammatory conditions, including allergic rhinitis and chronic rhinosinusitis – with and without polyposis. Paranasal sinuses serve as a NO ‘reservoir’, with concentrations typically exceeding those measured in lower airway (fractional exhaled NO or FeNO) by a few orders of magnitude. However, the dynamics of NO flux between the paranasal sinuses and main nasal airway, which are critical to respiratory NO emission, are poorly understood.

Recent findings

Historically, NO emissions were thought to be contributed mostly by the maxillary sinuses (the largest sinuses) and active air movement (convection). However, recent anatomically-accurate computational modeling studies based on patients’, CT scans showed that the ethmoid sinuses and diffusive transport dominate the process.

These new findings may have a substantial impact on our view of nasal NO emission mechanisms and sinus physiopathology in general.
Spinal drain for aortic aneurysm repairs: tool or toy?
Authors: Bastug Nicholas , Worrall Eric , Webb Laura , Larson Robert
Published: November 2022

Purpose of review

Spinal cord injury (SCI) is one of the biggest complications in open and endovascular aortic repairs. Historically, cerebrospinal fluid drains (CSFD) have been one of the most effective modalities in reducing SCI and one of the most studied. CSFD placement also carries its’ own set of procedural risks. This editorial intends to evaluate recent literature to determine whether CSFDs remain a valuable tool in aortic repair.

Recent findings

As the surgical management of thoracic aortic aneurysms has evolved, there has been an increasing number of endovascular repairs. Current recommendations emphasize prophylactic CSFD placement in endovascular repair cases deemed ‘high risk.’ However, several meta-analyses differ on whether prophylactic CSFD placement reduced the risk of SCI. The incidence of SCI decreased between 2014 and 2018, despite a similar rate of prophylactic CSFD placement suggesting other techniques are being performed and may be effective in spinal cord protection as well.

There has been conflicting data on whether CSFDs have a role in reducing the risk of SCI in endovascular aortic repair. Some studies suggest that there is no benefit to placement while others suggest that routine prophylactic drains should be placed for all endovascular cases. Despite this, efforts have been made to selectively place CSFDs in those patients deemed at ‘high risk’ for SCI. CSFDs also remain a part of rescue treatment for postoperative SCI. This suggests that CSFDs continue to be a valuable tool that we need to better comprehend. Future research is necessary to better understand how patient risk factors can be balanced with perioperative management to help identify patients who may benefit from CSFD placement.
Association of symptomatic late-onset hypogonadism and lower urinary tract symptoms in aging males: a community-based study
Authors: Liang Guo-Qing , Li Jian-Hui , Shi Hui-Juan , Zheng Jun-Biao , Yu Xiao-Hua , Zhang Shu-Cheng , Li Zheng , Zhu Qian-Xi , Song Yu-Xuan , Jiang Feng , Zhu Yong
Published: November 2022

Objective:

Testosterone deficiency may be a risk factor for lower urinary tract symptoms (LUTS), and there may be a causal link between the emergence of LUTS and the incidence of late-onset hypogonadism (LOH). We performed an epidemiologic study to investigate the association between symptomatic late-onset hypogonadism (SLOH) and LUTS in middle-aged and elderly rural Chinese males.

Methods:

A total of 965 men completed a questionnaire and underwent a detailed physical examination. The Aging Males’ Symptoms (AMS) scale was used to assess SLOH, and the International Prostate Symptom Score (IPSS) questionnaire was used to assess LUTS. Serum reproductive hormone levels of testosterone, sex hormone-binding globulin (SHBG) and luteinizing hormone (LH) were measured.

Results:

A total of 965 males (mean age: 56.34 ± 8.85, range: 40–80 years) were recruited for the present study. A total of 20.93% (202/965) were diagnosed with SLOH. A total of 93.16% (899/965) had mild LUTS, 5.18% (50/965) had moderate LUTS, and 1.66% (16/965) had severe LUTS. Among SLOH patients, 13.40% (27/202) and 3.90% (8/202) had moderate and severe LUTS, respectively. Patients with severe LUTS had increased SHBG and LH compared with those with mild and moderate LUTS (P <0.01). Correlation analysis revealed that the AMS total score was positively correlated with the IPSS score (P <0.05). The prevalence of SLOH was significantly increased with LUTS severity. In addition to the known effect of age, the results of multiple regression analysis also showed that serum LH or SHBG appeared to have a weak link with SLOH and LUTS that requires etiological and biological clarification in our future study.

Conclusion:

In this cross-sectional analysis of SLOH and LUTS, LUTS severity was significantly associated with hypogonadism symptoms. Additionally, the prevalence of SLOH advanced with increasing LUTS severity. Serum SHBG or LH showed a positive correlation with SLOH and LUTS.
Monitoring recovery of tree diversity during tropical forest restoration: lessons from long-term trajectories of natural regeneration
Authors: Chazdon Robin L. , Norden Natalia , Colwell Robert K. , Chao Anne
Published: November 2022

Given the importance of species diversity as a tool for assessing recovery during forest regeneration and active restoration, robust approaches for assessing changes in tree species diversity over time are urgently needed. We assessed changes in tree species diversity during natural regeneration over 12–20 years in eight 1-ha monitoring plots in NE Costa Rica, six second-growth forests and two old-growth reference forests. We used diversity profiles to show successional trajectories in measures of observed, asymptotic and standardized tree diversity and evenness as well as sample completeness. We randomly subsampled 1-ha plot data to evaluate how well smaller spatial subsamples would have captured temporal trajectories. Annual surveys in eight 1-ha plots were missing substantial numbers of rare or infrequent species. Older second-growth sites showed consistent declines in tree diversity, whereas younger sites showed fluctuating patterns or increases. Subsample areas of 0.5 ha or greater were sufficient to infer the diversity of abundant species, but smaller subsamples failed to capture temporal trajectories of species richness and yielded positively biased estimates of evenness. In tropical forest regions with high levels of diversity, species diversity from small sample plots should be assessed using methods that incorporate abundance information and that standardize for sample coverage.

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
The framework species method: harnessing natural regeneration to restore tropical forest ecosystems
Authors: Elliott Stephen , Tucker Nigel I. J. , Shannon Dia Panitnard , Tiansawat Pimonrat
Published: November 2022

As interest in restoring tropical forests surges, so does the need for effective methods to ensure success. The framework species method (FSM) restores forest ecosystems by densely planting open sites, close to natural forest, with woody species, indigenous to the reference ecosystem and selected for their ability to accelerate ecological succession. Criteria for selecting framework species include: (i) representative of the reference forest ecosystem, (ii) tolerant of open conditions, (iii) ability to suppress weeds, (iv) attractiveness to seed-dispersing animals and (v) easily propagated. The method is effective where forest remnants and viable populations of seed dispersers remain. The origins and elements of the FSM are discussed. We review its adoption in 12 countries. Adherence to original principles was mostly high, but some misuse of the term was evident. The need for clearer definitions was identified. We place the FSM on a scale of restoration methods, matched with degradation levels and compare its establishment costs with those of other methods. Obstacles to its wider adoption, both technical and socio-economic, are discussed, along with how these might be overcome. Finally, the FSM is more clearly defined to facilitate its use in contributing towards the goals of the UN Decade on Restoration.

This article is part of the theme issue ‘Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration’.
Clinical Evaluation of the GeneXpert®Xpert®Xpress SARS-CoV-2/Flu/RSVPLUSCombination Test
Authors: Johnson Grant , Gregorchuk Branden S.J. , Zubrzycki Arek , Kolsun Kurt , Meyers Adrienne F.A. , Sandstrom Paul A. , Becker Michael G.
Published: November 2022

The GeneXpert®Xpert®Xpress SARS-CoV-2/Flu/RSVPLUScombination test (PLUSAssay) received Health Canada approval in January 2022. ThePLUSAssay is similar to the SARS-CoV-2/Flu/RSV combination test, with modifications to improve assay robustness against circulating and emerging variants. The performance characteristics of thePLUSAssay were assessed at the Lakeridge Health Oshawa Hospital Centre and the National Microbiology Laboratory of Canada. ThePLUSAssay was directly compared to the SARS-CoV-2/Flu/RSV combination test using SARS-CoV-2 culture from five variants and remnant clinical specimens collected across the COVID-19 pandemic. This included 50 clinical specimens negative for all pathogens, 110 clinical specimens positive for SARS-CoV-2, Influenza A, Influenza B, RSVA, and/or RSVB and an additional 11 mixed samples to screen for target interactions. ThePLUSAssay showed a high percent agreement with the widely used SARS-CoV-2/Flu/RSV combination test. Based on these findings, thePLUSAssay and the Xpert SARS-CoV-2/Flu/RSV combination test results are largely consistent with no observed difference in sensitivity, specificity, or time to result when challenged with various SARS-CoV-2 variants. The reported Ct values provided by the newPLUSAssay was also unchanged, with the exception of a possible 1-2 decrease reported Ct for RSVA across a limited sample size.