bluuebunny/crossref_metadata_2025_split huggingface dataset:
RADI-08. Elucidating the Electrophysiology of Intraoperative Radiotherapy – Experience from Two Cases
Authors: Sener Ugur , Dabir Aman , Cifarelli Christopher 
Published: August 2021

Abstract
Brain metastases require multimodality treatment, often combining surgical resection, radiation therapy, and individualized systemic pharmacotherapy based on oncogenic drivers. Intraoperative radiation therapy (IORT) is an emerging treatment option where radiation is delivered directly to the resection cavity at the time of surgery. We present two patients who underwent electrocorticography (ECoG) during IORT, providing information regarding electrophysiologic safety and tolerability of the technique.
In the first case, a 65-year-old woman underwent resection of a hemorrhagic right occipital metastasis from non-small cell lung cancer. IORT was administered over sixteen minutes for a surface dose of 30 Gy.
In the second case, a 73-year-old man with underwent resection of a right posterior frontal metastasis from non-small cell lung cancer. IORT was delivered over eleven minutes for a surface dose of 30 Gy.
In both cases, a 1x6 contact array of subdural electrodes was placed adjacent to the planned field of radiation. Electrocortigraphy (HFF 70 Hz, TC 0.3 sec, sensitivity 150uV/mm) was obtained from the array two minutes prior to initiation of therapy, during therapy, and two minutes after completion of therapy in both cases. We found that IORT did not induce electrophysiological change in the tissue surrounding it in both cases with no epileptiform or ictal discharges during 20 minutes of ECoG recording around the time radiation therapy, nor did the patients have episodes suggestive of epileptic seizures in the acute post-operative period. One of the patients (case 1) experienced a single epileptic seizure 4 months after IORT, but this was temporally related to a new intraparenchymal hemorrhage and unlikely due to radiation therapy. These two cases illustrate the relative safety of IORT with respect to induction of immediate epileptiform changes within the brain parenchyma.
RADI-10. Is there any benefit for post-operative radiation in brain metastases? A systematic review and meta-analysis of Randomized controlled trials
Authors: Bolem Nagarjun , Soon Yu Yang , Ravi Sreyes , Teo Kejia , Nga Vincent Diong Weng , Lwin Sein , Yeo Tseng Tsai , Vellayappan Balamurugan 
Published: August 2021

Abstract

Purpose
The benefits of adding upfront post-operative radiation (either whole-brain or cavity radiation) have been debated, particularly due to the possible detriment in cognition post-radiation. We sought to compare the efficacy and safety between the surgical resection of brain metastases (BM) plus radiotherapy versus surgical resection alone.

Materials and Methods
We searched various biomedical databases from 1983 to 2019, for eligible randomized controlled trials (RCT). Outcomes studied were local recurrence (LR), overall survival (OS), and serious (Grade 3 +) adverse events (AE). We used the random-effects model to pool outcomes. The methodological quality of each study was assessed using the Cochrane Risk of Bias tool.

Results
We included 5 RCTs comprising of 673 patients. The odds ratio (OR) for LR ranged from 0.06–0.34 with a pooled odds ratio of 0.26 (95% confidence interval (CI) 0.19–0.37, P&lt; 0.001), strongly favoring the patients who received postoperative radiation. The overall survival (OS) was only reported in 3 studies and did not show any significant difference. The hazard ratio (HR) ranged from 1.01–1.29 with a pooled HR of 1.1 (95% CI 0.90–1.34, P=0.37). The treatment-related toxicities were inconsistently reported to draw any meaningful conclusions. The risk of bias was predominantly due to the lack of blinding and was deemed to be high, affecting all outcomes.

Conclusion
Our analysis confirms that postoperative radiation should be recommended after surgical resection of BM, for it significantly reduces the risk of local recurrence. However, we did not find any improvement in OS, suggesting that improvements in local control at the tumor bed alone may not impact survival. Balancing local control, and possible neuro-cognitive effects of whole-brain radiation, post-operative cavity radiation seems to be an attractive option.
RADI-12. Deep learning for automatic detection and contouring of metastatic brain tumors in stereotactic radiosurgery: a retrospective analysis with an FDA-cleared software algorithm
Authors: Wang Jen-Yeu , Sandhu Navjot , Mendoza Maria , Lin Jhih-Yuan , Cheng Yueh-Hung , Chang Yu-Cheng , Liang Chih-Hung , Lu Jen-Tang , Soltys Scott , Pollom Erqi 
Published: August 2021

Abstract

Introduction
Artificial intelligence-based tools can significantly impact detection and segmentation of brain metastases for stereotactic radiosurgery (SRS). VBrain is a deep learning algorithm, recently FDA-cleared, to assist in brain tumor contouring. In this study, we aimed to further validate this tool in patients treated with SRS for brain metastases at Stanford Cancer Center.

Methods
We included randomly selected patients with brain metastases treated with SRS from 2008 to 2020. Computed tomography (CT) and axial T1-weighted post-contrast magnetic resonance (MR) image data were extracted for each patient and uploaded to VBrain. Subsequent analyses compared the output contours from VBrain with the physician-defined contours used for SRS. A brain metastasis was considered “detected” when the VBrain “predicted” contours overlapped with the corresponding physician contours (“ground-truth” contours). We evaluated performance against ground-truth contours using the following metrics: lesion-wise Dice similarity coefficient (DSC), lesion-wise average Hausdorff distance (AVD), false positive count (FP), and lesion-wise sensitivity (%).

Results
We analyzed 60 patients with 321 intact brain metastases treated over 70 SRS courses. Resection cavities were excluded from the analysis. The median (range) tumor size was 132 mm3 (7 to 24,765). Input CT scan slice thickness was 1.250 mm, and median (range) pixel resolution was 0.547 mm (0.457 to 0.977). Input MR scan median (range) slice thickness was 1.000 mm (0.940 to 2.000), and median (range) pixel resolution was 0.469 mm (0.469 to 1.094). In assessing VBrain performance, we found mean lesion-wise DSC to be 0.70, mean lesion-wise AVD to be 9.40% of lesion size (0.805 mm), mean FP to be 0.657 tumors per case, and lesion-wise sensitivity to be 84.5%.

Conclusion
Retrospective analysis of our brain metastases cohort using a deep learning algorithm yielded promising results. Integration of VBrain into the clinical workflow can provide further clinical and research insights.
RADI-20. Brain metastasis treatment with high energy radiotherapy and Cherenkov radiation-activated phototherapy
Authors: Price Anna L , Holden Russell , Park James J H , Dunn Denise , Koch Brendan , Oldham Mark , Floyd Scott R 
Published: August 2021

Abstract
Radiation therapy is a mainstay in the treatment of brain metastasis, yet some tumors are resistant, and elsewhere brain recurrence outside the radiation field is common. Phototherapy using UV light-activated compounds can both kill cancer cells directly and trigger an immune response to extend tumor control. Poor penetration depth of ultraviolet light, however, has limited this treatment to superficial tumors. High-energy photon beams create high energy electrons within the patient which in turn produce Cherenkov radiation in the UV spectrum while traveling through tissue. Given that this Cherenkov radiation is generated deep within the patient and has the ability to activate photosensitive compounds, we therefore developed a platform to test this phenomenon to enhance radiation therapy for brain metastasis.
We first tested UV-activated psoralen derivatives in combination with UV light in vitro for activity against murine 4T1 breast cancer cells, and then irradiated an ex vivo organotypic brain slice platform using a high energy linear accelerator to generate Cherenkov radiation. We tested the survival of 4T1 cells expressing fluorescent and bioluminescent reports in the presence and absence of these psoralen compounds in this ex vivo brain metastasis model.
8-methoxypsoralen (8-MOP) and 4’-Aminomethyltrioxsalen hydrochloride (AMT) both showed 365nm UVA light-specific cell killing in vitro. We optimized AMT cell loading (1 hour) and concentrations [1μM] AMT to maximize cytotoxicity. Testing of AMT using the organotypic brain slice platform and high-energy irradiation to generate Cherenkov-UV light demonstrated similar enhanced cell death of 4T1 cells despite high baseline levels of radiation-induced tumor cell kill.
Cherenkov radiation-induced photo-activation of AMT improved cell killing in an ex vivo model of breast cancer brain metastasis. This application holds promise for the re-treatment of refractory tumors with high-energy, low dose radiation, and enhanced elsewhere brain metastasis control through activation of the immune system.
SURG-01. Management of solitary brain metastasis less than 4 cm in diameter. Surgical resection versus stereotactic radiotherapy: a meta-analysis
Authors: Krist David T , Naik Anant , Kwok Susanna S , Janbahan Mika , Olivero William C , Thompson Charee M , Hassaneen Wael 
Published: August 2021

Abstract

Introduction
To treat a solitary metastasis in the brain, surgical resection and/or radiotherapy are the standard treatments of care. However, the clinical scenarios in which to use these techniques alone or in combination are controversial. While a course of stereotactic radiotherapy is often administered to a patient who presents with multiple metastases, surgical resection is often directed against a larger solitary brain metastasis before irradiating the resection bed. The management of a smaller solitary tumor (diameter less than 4 cm) is less clear. Accordingly, our meta-analysis assembled studies that focused on patients with a solitary tumor less than 4 cm in diameter.

Methods
Following PRISMA guidelines (PROSPERO ID: CRD42021242434), we searched PubMed, Web of Knowledge, and Cochrane Library databases for randomized controlled trials (RCT) and observational studies comparing surgery to radiotherapy for solitary metastatic brain tumors less than 4 cm in diameter. From 498 total records, we included 9 studies for meta-analysis. Analysis was performed on R.

Results
2 RCTs and 7 observational studies were identified. 431 patients underwent surgical intervention, and 349 patients exclusively underwent radiotherapy. The surgical treatment cohort did not exhibit a difference in 1-year (OR [95% CI] = 0.866 [0.609–1.289]), 2-year (1.7 [0.843–3.428]), or overall survival (1.18 [0.598–2.327]). However, the surgical treatment group demonstrated greater local tumor recurrence after 1-year (3.975 [1.979–7.987]) and overall local recurrence (3.045 [1.276 - 7.268]). There was no difference between the overall rates of distant recurrence (0.565 [0.218 - 1.466]).

Conclusions
Our analysis opens more discussion about the management of solitary brain metastasis. Patient selection is paramount in achieving better local control. Stereotactic radiotherapy should be considered for treatment of solitary brain metastasis less than 4 cm in diameter in selected patients. Future randomized control trials for small solitary masses are recommended.
SURG-13. Multiplicity does not affect outcomes in patients with surgically treated brain metastases
Authors: Yang Kaiyun , Gutierrez Enrique , Landry Alexander , Kalyvas Aristotelis , Weiss Jessica , Shultz David , Kongkham Paul 
Published: August 2021

Abstract

Background
Having multiple brain lesions has been considered a negative prognostic factor in patients with brain metastases. The role of surgery in the management of these patients remains a matter of debate.

Methods
We retrospectively reviewed our patients who underwent surgical resection of brain metastases from January 2018 to December 2019, and examined outcomes including overall survival (OS), progression free survival (PFS) and rates of local failure.

Results
We identified 130 patients who underwent surgical resection as the primary treatment modality of brain metastases. At the time of surgery, 117 patients harbored 1–3 lesions, 13 had more than 3 lesions. Overall survival at two years for our entire cohort was 46%. The difference in OS between patients with &gt; 3 metastases (21%) and 1–3 metastases (49%) was not statistically significant (HR=1.34, 95% CI: 0.67–2.68, p=0.41). Similarly, 27% of patients had PFS at two years, with 25% in the multiple metastases group and 28% in the comparison group (HR=1.19, 95% CI: 0.63–2.23, p=0.59). Additionally, 32% of patients overall experienced local failure at two years and there was no significant difference between patients with &gt;3 metastases (15%) and those with fewer (33%) (HR=0.68, 95% CI: 0.21–2.19, p=0.52). A multivariate regression model examining multiple preoperative features revealed large tumor volume to be the only independent predictor of limited OS (p = 0.017) and PFS (p = 0.023), and local failure (p = 0.031).

Conclusions
In carefully selected patients, surgical resection is a reasonable management option for patients with multiple brain metastases.
SURG-14. Laser Ablation for Brain Metastases: Risk Factors for Neurologic Complication
Authors: Pawloski Jacob , Fadel Hassan , Haider Sam , Rogers Lisa , Lee Ian , Robin Adam 
Published: August 2021

Abstract

Introduction
Laser interstitial thermal therapy (LITT) is a routinely used in treatment of recurrent brain metastases following SRS or open craniotomy. While considered safer than craniotomy, patients do experience neurologic decline following LITT. Identifying which patients are at risk for neurologic deterioration can help better advise patients on the most appropriate treatment options for their tumor.

Objective
The objective of the present study was to assess the frequency and identify risk factors for neurologic decline following LITT.

Methods
Data was gathered on patients who underwent LITT for ablation of metastatic brain tumors at our institution between 2014–2019. These cases were analyzed retrospectively and data was collected on patient demographics, tumor characteristics, procedural details, and post-operative complications and outcomes. Pre-operative neurologic function was compared to neurologic status at the 6–12 week post-op visit.

Results
16 patients underwent LITT of a total of 18 metastatic lesions during the study time period and were included in the analysis. 7/16 patients demonstrated reduced KPS or worse neurologic function at 6–12 week follow up. 4 patients (25%) demonstrated neurologic deficits that were attributable to the laser ablation procedure, and each of these 4 patients had lesions in eloquent areas. Comparatively, none of the other 12 patients analyzed had eloquent lesions (p = 0.002). The presence of a pre-op neurologic deficit was not predictive of worsening neurologic function following LITT (p = 0.35). Average lesion size in patients who experienced neurologic deficit was 5.69cm3 compared to 3.15cm3 in those that did not (p = 0.1).

Conclusion
Our complications rate is similar to other published case series (15–44%). LITT, while better tolerated than standard craniotomy, can lead to neurologic decline in patients with brain metastases regardless of lesion size or pre-operative functional status. Eloquence is a significant predictor of neurologic complications following laser ablation.
A closed class? Powers to appoint further beneficiaries as a constraint on the rule in Saunders v Vautier
Authors: Johnson Jeremy , Halligan Jordan 
Published: August 2021

Abstract
One constraint on the rule in Saunders v Vautier is that, where the trusts include discretionary trusts, the class of beneficiaries must be closed, so it is possible to determine who may legitimately benefit from, and thereby terminate, the trusts. At common law, it is unclear whether a power to appoint further beneficiaries may therefore frustrate the operation of the rule. This article examines the provisions of the Trusts Act 2019 (New Zealand) in the context of a recent decision of the courts in Guernsey, which suggests that the Act may have inadvertently altered the common law position.
Therapeutic Drug Monitoring of Antimicrobial Drugs in Neonates: An Opinion Article
Authors: Touw Daan J. , van den Anker John N. 
Published: August 2021

Background:
Neonatal infections are associated with high morbidity and mortality rates. Optimal treatment of these infections requires knowledge of neonatal pharmacology and integration of neonatal developmental pharmacokinetics (PKs) of antimicrobial drugs in the design of dosing regimens for use with different gestational and postnatal ages. Population PK and pharmacodynamic models are used to personalize the use of these drugs in these fragile patients. The final step to further minimize variability in an individual patient is therapeutic drug monitoring (TDM), where the same population PK/pharmacodynamic models are used in concert with optimally drawn blood samples to further fine-tune therapy. The purpose of this article is to describe the present status and future role of model-based precision dosing and TDM of antimicrobial drugs in neonates.

Methods:
PubMed was searched for clinical trials or clinical studies of TDM in neonates.

Results:
A total of 447 articles were retrieved, of which 19 were concerned with antimicrobial drugs. Two articles (one aminoglycoside and one vancomycin) addressed the effects of TDM in neonates. We found that, in addition to aminoglycosides and vancomycin, TDM also plays a role in beta-lactam antibiotics and antifungal drugs.

Conclusions:
There is a growing awareness that, in addition to aminoglycosides and vancomycin, the use of beta-lactam antibiotics, such as amoxicillin and meropenem, and other classes of antimicrobial drugs, such as antifungal drugs, may benefit from TDM. However, the added value must be shown. New analytical techniques and software development may greatly support these novel developments.
Artificial intelligence and machine learning in aortic disease
Authors: Hahn Lewis D. , Baeumler Kathrin , Hsiao Albert 
Published: August 2021

Purpose of review
Discuss foundational concepts for artificial intelligence (AI) and review recent literature on its application to aortic disease.

Recent findings
Machine learning (ML) techniques are rapidly evolving for the evaluation of aortic disease – broadly categorized as algorithms for aortic segmentation, detection of pathology, and risk stratification. Advances in deep learning, particularly U-Net architectures, have revolutionized segmentation of the aorta and show potential for monitoring the size of aortic aneurysm and characterizing aortic dissection. These algorithms also facilitate application of more complex technologies including analysis of flow dynamics with 4D Flow magnetic resonance imaging (MRI) and computational simulation of fluid dynamics for aortic coarctation. In addition, AI algorithms have been proposed to assist in ‘opportunistic’ screening from routine imaging exams, including automated aortic calcification score, which has emerged as a strong predictor of cardiovascular risk. Finally, several ML algorithms are being explored for risk stratification of patients with aortic aneurysm and dissection, in addition to prediction of postprocedural complications.

Summary
Multiple ML techniques have potential for characterization and risk prediction of aortic aneurysm, dissection, coarctation, and atherosclerotic disease on computed tomography and MRI. This nascent field shows considerable promise with many applications in development and in early preclinical evaluation.
Factors Associated With Laser Trabeculoplasty Response Duration: Analysis of a Large Clinical Database (IRIS Registry)
Authors: Chang Ta Chen , Vanner Elizabeth A. , Fujino Danielle , Kelly Scott , Parrish Richard K. 
Published: August 2021

Précis:
In eyes with trabeculoplasty response, those with lower baseline pressure, angle recession or uveitis had shorter survival. Eyes without medications before treatment remained medication-free for a median of 197 days.

Purpose:
We examined patients in a large clinical registry to assess factors associated with laser trabeculoplasty (LTP) response durations.

Methods:
This is a retrospective cohort study with LTP patients in the Intelligent Research in Sight Registry. Data were extracted if the eye had a LTP procedure code and a glaucoma diagnosis. In responders [≥20% intraocular pressure (IOP) reduction], any post-LTP IOP that was above 80% of baseline was considered a failure event. Eyes were censored if IOP-lowering medication/procedure was added/performed, or if the eye reached the end of follow-up. First eye of bilaterally treated patients were included.

Results:
A total of 79,332 patients/eyes were included; 53.2% female; mean age 71.5 years; 64.5%White; 71.2% primary open angle glaucoma. Mean baseline IOP was 21.6±5.3 mm Hg (2.1±1.5 medications). Eyes with higher baseline IOP had longer survival (>24 mm Hg median 349 d; 18 to 24 mm Hg median 309 d; <18 mm Hg median 256 d, P<0.001 for all comparisons). Overall failure at 0, 6, 12, 18 and 24 months were 0.2%, 6.1%, 16.8%, 29.1%, and 40.8%. Angle recession and uveitis increased the risk of failure (hazard ratios 1.69 and 1.80, respectively). Eyes without medications at baseline remained medication-free for a median of 197 days (interquartile range 106, 395 d).

Conclusions:
Angle recession and uveitis increase the risk of LTP failure. LPT may be effective in prolonging medication-free IOP-control in some patients.
The evolving role of advanced practice providers in transplantation: a literature review
Authors: Nargiso Sarah , Tristan Vincent , Ramos Leyda , Muriel Jaira A. , Sachs Robert E. 
Published: August 2021

Purpose of review
Solid organ transplantation is a life-saving procedure, often performed in critically ill patients, and advanced practice providers (APPs) have increasingly been incorporated into the multidisciplinary transplant team. A literature review was performed and reinforces the value of transplant APPs, details their evolving roles and responsibilities, and highlights innovative solutions created to address complex problems.

Recent findings
The literature review revealed a deficit of quality quantitative data supporting the utilization of APPs in transplantation. Thus, data regarding the value of APPs in critical care was also analyzed.

Summary
The limited data despite decades long integration of transplant APPs into the multidisciplinary team, suggests there are likely positive outcomes and innovations that go undocumented. Thus, there are missed opportunities for learning and improvement. Transplant programs investing time and mentorship to support APP research will identify strengths and weaknesses within our existing care models, discover cost saving innovations, and continue to optimize the role of APPs in delivering high quality care that is efficient and evidence based.