bluuebunny/crossref_metadata_2025 huggingface dataset:
THER-02. PARP Inhibitor Tolerability and Impact on Progression-Free Survival in Patients with High-Grade, Ovarian Carcinoma with Brain Metastasis: A Case-Series
Authors: Mohler Alexander , Salinas Belkys , Nazur Karissa , Odia Yazmin , Lambrou Nicholas
Published: August 2021

Brain metastases secondary to ovarian carcinoma is an uncommon but increasing phenomenon. PARP inhibitors (PARPi) are increasingly used as an adjunctive treatment in patients with central nervous system metastases (CNS). Historically brain metastases has a historically poor prognosis.

Five women with a mean age of 60.4 ± 7.6 years were included. All had stage IIIC/IV ovarian cancer and diagnosed with brain metastases at recurrence. Three underwent resection for oligometastatic disease followed by post-operative stereotactic radiosurgery (SRS), one had SRS without surgery, and one patient underwent whole brain radiotherapy for multiple metastases. Pathology was confirmed in those who were resected. Two patients had evidence of systemic disease in addition to CNS spread. Three women were BRCA1/2 Positive.

Following initial radiotherapy, one patient received adjuvant chemotherapy followed by olaparib maintenance, one received 13 cycles of bevacizumab/olaparib, followed by olaparib maintenance. A third patient was treated with olaparib/bevacizumab and two patients received olaparib monotherapy, both of whom continued on therapy. All received olaparib therapy during their treatment and all had minor dose modifications due to side effects. Mean survival from initial cancer diagnosis was 62.4 ± 20.4 months. Mean duration of PARPi therapy was 27.6 ± 16.8 months. Mean survival following CNS recurrence was 22.8 ± 12 months. One patient is disease-free, two patients are alive with stable disease, one patient is alive but off treatment secondary to progression, and one patient is deceased secondary to progression of her brain metastases after being on PARP therapy for 18 months. The cohort remained highly functional across the trajectory of their disease with ECOG scores of 1 (n=4) or 0 (n=1).

The results of this single institution retrospective evaluation suggest olaparib in combination with radiotherapy +/- bevacizumab is well tolerated and can provide additional benefit in patients with brain metastases secondary to ovarian carcinoma.
MLTI-03. The relevance of the count of brain metastases for treatment and outcome in NSCLC
Authors: Reinecke David , Jünger Stephanie T , Kocher Martin , Ruge Maximilian , Ruess Daniel , Goldbrunner Roland , Grau Stefan J
Published: August 2021

Background and Purpose

While data reporting the number of brain metastasis as a prognostic factor for patients with NSCLC, we analyzed whether the prognostic importance of the mere count of brain metastasis in a modern, multimodal treatment setting.

Patients and Methods

We retrospectively analyzed patients treated for BM from non-small lung cancer between 2010 and 2020. Demographics, baseline characteristics, and tumor-associated parameters were retrieved from an electronic database. Prognostic factors for local cerebral control and survival were identified using the log-rank test and Cox regression analysis.

Results

We included 343 consecutive patients (male n=187, female n=156; median age 61 years). Histological subtypes were adenocarcinoma (n=283), squamous-cell carcinoma (n=42) and neuroendocrine carcinoma (n=18). The median number of BM was one (range 1–20). Single (n = 189), oligo (n=110) and multiple BM (n=44) showed in total a median follow up of 10 months (minimum 1, maximum 142). Treatment comprised surgical resection (n=218) with radiotherapy, stereotactic radiosurgery (n=125) and adjuvant systemic therapy (n=203). The median local cerebral control was 11 months (95%CI 8.5 – 13.5) and the median overall survival was 16 months (95%CI 12.8 – 19.2). The number of BM did not influence local control and overall survival rates (p = 0.234 and p = 0.210, respectively). Controlled systemic disease (HR 0.42; 95% CI 0.2284–0.633; p<0.0001), clinical status (Karnofsky Performance Score > 70; HR 0.41; 95% CI 0.265–0.661; p<0.0001) and adjuvant systemic therapy (HR 0.38; 95% CI 0.279–0.530; p<0.0001) were independent prognostic factors for survival.

Conclusions

The mere number of brain metastases is not a prognostic factor for survival and local cerebral control in a multimodal treatment setting.
MLTI-04. The Role of the Outpatient Registered Nurse in the care of Brain Metastases
Authors: Hernandez Juliana , Lavarco Amanda , David Kurt
Published: August 2021

Introduction

Brain metastases is a complex disease, requiring a skilled clinical team to deliver medical and surgical care. The nurse is an integral member of the interdisciplinary team. Despite this, the role of the nurse in brain metastasis care has been neglected in the literature. Moreover, while education for neurology nursing exists, there is a paucity of literature defining the nursing care specific to brain metastases. The aim of this study was to describe the essential nursing functions in brain metastases within medical and surgical clinics.

Methods

A working-group comprised of 2 registered nurses and a clinical nurse specialist in specialty brain metastases at Memorial Sloan-Kettering Cancer Center was formed. A KSA framework was used to develop a survey to assess nurses’ knowledge, skills, and attitudes regarding care of patients with brain metastases. 2 nurses were surveyed. Oncology nursing competencies were scored by medicine and surgical nurses for importance. Mean scores were calculated and ranked.

Results

Nurses consistently reported care coordination; symptom management and monitoring parameters; knowledge of treatment modalities; and referrals as key competencies. More variably endorsed competencies included access devices (implanted port and Omaya); managing immunocompromised patients; and legal issues (consent).

The nurses reported important knowledge includes screening and treatment guidelines; epidemiology; disease states including brain metastases and leptomeningeal disease; and tumor histology. Important skills include neurological exam; triage; critical thinking; and patient education. Important attitudes include being empathetic, communicative, positive, truthful, and realistic.

Conclusion

As the care of the patient with brain metastases evolves, interdisciplinary clinical practice models with advanced nursing training must occur. As the repertoire of clinical trials for patients with brain metastases continues to expand, future studies should assess the effects of specialized nursing training on clinical outcomes in patients with brain metastases.
MLTI-05. Adjuvant re-irradiation improves local control of surgically resected recurrent brain metastases
Authors: Wilcox Jessica , Brown Samantha , Reiner Anne , Young Robert , Chen Justin , Bale Tejus , Rosenblum Marc , Newman William , Brennan Cameron , Tabar Viviane , Beal Kathryn , Panageas Katherine , Moss Nelson
Published: August 2021

Background

The efficacy of salvage resection (SR) of recurrent brain metastases (BrM) post-stereotactic radiosurgery (SRS) is not well described. We sought to characterize the impact of adjuvant post-salvage radiation therapy (PSRT) in this setting and identify tumor-specific variables that influence local control.

Methods

Retrospective analysis of post-SRS recurrent BrM that underwent SR between 2003–2020 at Memorial Sloan Kettering Cancer Center was performed. Cases with histologically-viable malignancy were included and stratified by receipt of adjuvant PSRT within 60 days of SR (PSRT cohort) vs. observation (observation cohort). Resection-site outcomes were described using cumulative incidences and univariate and multivariate competing risks regression accounting for clustering.

Results

One-hundred fifty-five recurrent BrM in 135 patients were included. Thirty-nine (25.2%) of the post-operative cavities were treated with adjuvant PSRT, and the remaining 116 (74.8%) cavities were initially observed. Gross- or near-total resection was associated with significantly improved local control compared to subtotal resection (p=0.007). Adjuvant PSRT was associated with a reduced rate of LR at 6 months [18.0% (95%CI: 9.8–33.1%) vs. 35.9% (95%CI: 27.9–46.2%) with initial observation] and 12 months [28.8% (95%CI: 17.0–48.8%) vs. 43.9% (95%CI: 36.2–53.4%)]. On multivariate analysis, adjuvant PSRT (p=0.095), low tumor-viability within the resected BrM (p=0.17), and first-time resection (p=0.035) all independently trended towards improved local control. BrM size at SR (≥3cm vs. <3cm, p=0.48), primary malignancy (p=0.35), and specific PSRT modality (whole or partial brain radiation vs. SRS, p=0.43) were not associated with differences in LR rate. Radiation necrosis (RN) was significantly increased in the PSRT cohort (HR 4.55, 95%CI: 1.26–16.39, p=0.02), though the total percentage with symptomatic RN remained low (PSRT cohort 5.1% vs observation cohort 0.9%).

Conclusions

Local control after SR of a recurrent BrM may be optimized with gross- or near-total resection and adjuvant post-operative re-irradiation, with low symptomatic RN.
OTHR-09. Accelerating Research for Breast Cancer Brain Metastasis and Leptomeningeal Disease through Patient-led Collaborations
Authors: Hodgdon Christine , Campbell Laurie
Published: August 2021

Patient-driven Initiative of the Metastatic Breast Cancer (MBC) Alliance

The Breast Cancer Brain Metastasis (BCBM) Initiative: Marina Kaplan Project launched in June 2020 as an official project of the MBC Alliance which includes 32 nonprofits, 12 industry partners, and 30 individual patient advocates. The Marina Project has grown to include 35members with representation from industry, research institutions, and individual patients. Nearly one-third of the group is comprised of patients living with brain metastases or leptomeningeal disease (LMD).

Disparities for Patients Living with BCBM & LMD

In the US, approximately 200,000 new cases of brain metastases are diagnosed each year[1]. Approximately 10–15% of patients with MBC will develop brain metastases, and may be as high as 30–50% for certain subtypes[2].

A diagnosis of central nervous system (CNS) metastasis often accelerates an already incurable diagnosis. CNS metastasis are difficult to image and detect, tend to have poorer prognoses with lower overall survival, and are treated with invasive therapies which can have lasting side effects. Furthermore, most clinical trials exclude patients with CNS metastasis which further hinders research.

Values and Objectives

The overarching goal of this initiative is to accelerate the scope and breadth of evidence-based CNS metastasis research by targeting entities conducting clinical trials and collaborating with them to do the following:

(i) Increase the quality and quantity of basic research;

(ii) Increase the number of clinical trials in areas where research is lacking;

(iii) Diversify the type of clinical trial interventions;

(iv) Eliminate restrictive eligibility criteria in clinical trials;

(v) Incorporate clinically meaningful trial endpoints

[1] Eichler, April F et al. The biology of brain metastases-translation to new therapies. Nature reviews. Clinical oncology vol. 8,6 (2011): 344–56. doi: 10.1038/nrclinonc.2011.58

[2] Brosnan EM, Anders CK. Understanding patterns of brain metastasis in breast cancer and designing rational therapeutic strategies. Ann Transl Med. 2018;6(9):163. doi: 10.21037/atm.2018.04.35
OTHR-11. Comprehensive Analysis of Driver Mutation Profile in a Cohort of Lung Cancer Patients Using Targeted Gene Panel Analysis with Focus on Brain Metastatic Disease
Authors: Kazarian Marina , Cui Jin , Tocino Irena , Mahajan Amit , Aboian Mariam
Published: August 2021

Purpose

Approximately 228,820 people are diagnosed annually with lung cancer diagnosis and 135,720 die from their disease1. EGFR and KRAS targeted therapies have been shown to significantly improve treatment of non-small cell lung cancer (NSCLC), but they don’t apply to the majority of patients. There’s a critical need to characterize the molecular signature of patients with lung cancer and to define the proportion of patients eligible for novel targeted therapies.

Methods

IRB approval was obtained to retrospectively extract data from tertiary hospital tumor registry from 2011 to 2017. Data collected included patient demographics, targeted next generation sequencing results (50 and 150 gene panel), histology, and biopsy location in the final 2,203 patients, 715 of which were manually checked.

Findings

83.8% of patients in the lung cancer cohort that had targeted next-generation gene panel analysis demonstrated presence of at least one mutation. 50.9% of the patients in our cohort had a targetable mutation. There were 9.5% with hypermutated phenotype characterized as at least 5 mutations per sample. 1.3% of patients had at least 10 mutations per sample. We also characterize the distribution of mutations within brain metastatic lesions and demonstrate that brain metastases with hypermutated phenotype demonstrate larger volumes of edema and greater involvement of deep white matter than non-hypermutated brain metastases.

Conclusion

We present a comprehensive analysis of the molecular signature of lung cancer from a tertiary referral institution with focused analysis of brain metastases. Lung cancer brain metastases with greater than 5 mutations correspond to greater volume of edema and involvement of deep white matter.
RADI-08. Elucidating the Electrophysiology of Intraoperative Radiotherapy – Experience from Two Cases
Authors: Sener Ugur , Dabir Aman , Cifarelli Christopher
Published: August 2021

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

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< 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

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

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

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

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 > 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 >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

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

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.

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.
Long COVID in Children
Authors: Ashkenazi-Hoffnung Liat , Shmueli Einat , Ehrlich Shay , Ziv Adi , Bar-On Ophir , Birk Einat , Lowenthal Alexander , Prais Dario
Published: August 2021

Systematic data are lacking on pediatric long COVID. This study prospectively assessed 90 children with persistent symptoms who presented to a designated multidisciplinary clinic for long COVID. In nearly 60%, symptoms were associated with functional impairment at 1–7 months after the onset of infection. A comprehensive structured evaluation revealed mild abnormal findings in approximately half the patients, mainly in the respiratory aspect.
Bell’s Palsy and the Peril of Eponyms
Authors: Margo Curtis E.
Published: August 2021

The seemingly mundane management of a Bell’s palsy can have devastating consequences if the diagnosis of nonidiopathic cranial nerve palsy is not kept in perspective. The case of an elderly man mislabeled by a primary care physician as having a Bell’s palsy illustrates how eye physicians can prevent an adverse outcome. Unilateral incomplete eyelid exposure and ipsilateral progressive pain were this patient’s main problems for roughly 18 months during which time ophthalmologists managed his corneal exposure but failed to appreciate a parotid gland tumor. Eye physicians are in a unique position to recognized if a nonidiopathic cause of seventh cranial nerve palsy exists because they manage problems with corneal exposure. Replacing Bell’s palsy with the term idiopathic facial nerve palsy may heighten awareness that other causes of seventh cranial nerve palsy must be considered, but recounting an adverse outcome may also be a valuable learning experience.
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.

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.
Rotterdam Transition Test
Authors: van Gaalen Martha A.C. , van Pieterson Merel , van den Brink Gertrude , de Ridder Lissy , Rizopoulos Dimitris , van der Woude C. Janneke , Escher Johanna C.
Published: August 2021

Objectives:

Disease knowledge is important in adolescents with inflammatory bowel disease (IBD) transitioning to adult care. We developed an IBD‐specific knowledge questionnaire, the Rotterdam Transition Test (RTT), and aimed to validate this tool.

Methods:

This is a prospective longitudinal validation study. The RTT has 25 open questions on IBD, medication, lifestyle, and transition to adult care. A scoring model was developed, and inter‐rater agreement was assessed. Using a Rasch model, we determined the difficulty and performance of the questions. Cronbach alpha was used to demonstrate reliability. Patient factors (age, disease, education, medication use, illness acceptance, and independence) were correlated to RTT score.

Results:

A total of 207 RTTs were evaluated in 111 adolescent IBD patients. The scoring model showed a kappa score of >0.61 for all questions. Reliability with Cronbach alpha was good (0.81). Mean total result of the RTT was 58% (girls) and 55% (boys) of maximal score.

The RTT discriminated well between the different levels of knowledge. Knowledge scores increased in patients who did repeated RTTs during the transition period. Male sex, low educational level, disease acceptance issues, and dependence on parents associated with a significantly lower total RTT score. Prednisone use within 3 months and treatment without biologics associated with significantly higher RTT scores. Disease activity was not a significant factor.

Conclusions:

The RTT is a reliable and valid tool to assess IBD knowledge. The RTT can be used to detect and discuss knowledge gaps in adolescents with IBD transitioning to adult healthcare.
CT scans better assess lateral wall morphology of “stable appearing” intertrochanteric (IT) femur fractures and predict early failure of sliding hip screw (SHS) fixation
Authors: Hecht Garin , Saiz Augustine M. , Shelton Trevor J. , Haffner Max R. , Delman Connor , Shieh Alvin , Hallare Jericho , Bhatti Satninderdeep , Wolinsky Philip
Published: August 2021

Objectives:

To compare the efficacy of plain x-ray images and computed tomography (CT) to assess the morphology of the lateral wall (LW) component of intertrochanteric (IT) femur fractures and determine predictors of early fixation failure.

Design:

Retrospective cohort study.

Setting:

Level-one trauma center.

Patients/Participants:

One hundred forty-two adult patients with IT fractures treated with either a sliding hip screw (SHS) or a cephalomedullary nail (CMN) who had both pre-op plain x-ray images and CT scans with at least 6 weeks of follow-up were reviewed.

Intervention:

Preoperative CT scan and plain radiographs of the affected hip.

Main Outcome Measurements:

Lateral wall assessment based on plain x-rays versus CT imaging in relation to implant failure.

Results:

One hundred forty-two patients met inclusion criteria, 105 patients treated with a CMN, and 37 with a SHS. There was a poor correlation between the assessment of the LW on plain x-ray images and CT scans. Failures in the SHS group were significantly associated with all CT measurements (P < .05) but not with plain film LW assessment (P = .66). Fifteen patients had an early implant failure (6 CMN, 9 SHS). There were no statistically significant associations between any radiographic measurement (plain images and CT) and CMN failures.

Conclusions:

Plain film images are not accurate for assessing lateral wall morphology/integrity and are not predictive of SHS implant failures. Our novel CT measurements were effective at detecting lateral wall patterns at risk for treatment failure with SHS implants.

Level of Evidence: Level III
Biomarkers Obtained by Transcranial Magnetic Stimulation in Neurodevelopmental Disorders
Authors: Jannati Ali , Ryan Mary A. , Kaye Harper L. , Tsuboyama Melissa , Rotenberg Alexander
Published: August 2021

Transcranial magnetic stimulation (TMS) is a method for focal brain stimulation that is based on the principle of electromagnetic induction where small intracranial electric currents are generated by a powerful fluctuating magnetic field. Over the past three decades, TMS has shown promise in the diagnosis, monitoring, and treatment of neurological and psychiatric disorders in adults. However, the use of TMS in children has been more limited. We provide a brief introduction to the TMS technique; common TMS protocols including single-pulse TMS, paired-pulse TMS, paired associative stimulation, and repetitive TMS; and relevant TMS-derived neurophysiological measurements including resting and active motor threshold, cortical silent period, paired-pulse TMS measures of intracortical inhibition and facilitation, and plasticity metrics after repetitive TMS. We then discuss the biomarker applications of TMS in a few representative neurodevelopmental disorders including autism spectrum disorder, fragile X syndrome, attention-deficit hyperactivity disorder, Tourette syndrome, and developmental stuttering.
Cognitive Biomarkers in the Clinic: Lessons From Presurgical fMRI
Authors: Benjamin Christopher F. A.
Published: August 2021

Cognitive biomarkers are vital and uniquely challenging clinical tools. There has been marked growth in neuroimaging-based cognitive biomarkers across the past 40 years with more in development (e.g., clinical cognitive EEG). The challenges involved in developing cognitive biomarkers and key milestones in their development are reviewed here using clinical functional MRI's evolution as a case study. It is argued that indexing cognition is uniquely challenging because it requires patients to consistently use specific cognitive processes, and it is difficult or impossible to independently verify this occurred. This limitation can be successfully managed through careful analysis of standardized protocols for acquisition and interpretation, and ensuring the clinical application of biomarkers integrates disciplines with complementary expertise. Factors beneficial to the adoption of a novel cognitive biomarker include a clinical need and inadequate alternatives. Key milestones in the development of functional MRI included (1) demonstration that its performance was equivalent to its predecessor; (2) demonstration it predicted a clinically meaningful outcome; and (3) the establishment of infrastructure for both its execution and billing. Review of functional MRI and its predecessors suggest a cycle whereby successful cognitive biomarkers are validated, experience widespread adoption and customization/fragmentation, go through a period of review, and finally are refined and standardized. Those applying future cognitive biomarkers in the clinic can avoid some of the failures of clinical functional MRI by defining the skills and disciplines the method requires and routinely evaluating patient outcomes.
Optimized Flow Cytometric Detection of Transient Receptor Potential Vanilloid-1 (TRPV1) in Human Hematological Malignancies
Authors: Omari Sofia A , Geraghty Dominic P , Khalafallah Alhossain A , Venkat Pooja , Shegog Yvette M , Ragg Scott J , de Bock Charles E. , Adams Murray J
Published: August 2021

The ectopic overexpression of transient receptor potential vanilloid-1 (TRPV1) has been detected in numerous solid cancers including breast, prostate, pancreatic, and tongue epithelium cancer. However, the expression of TRPV1 in hematological malignancies remains unknown. Here we show through in silico analysis that elevated TRPV1 mRNA expression occurs in a range of hematological malignancies and present an optimized flow cytometry method to rapidly assess TRPV1 protein expression for both cell lines and primary patient samples. Three anti-TRPV1 antibodies were evaluated for intracellular TRPV1 detection using flow cytometry resulting in an optimized protocol for the evaluation of TRPV1 in hematological malignant cell lines and patients’ peripheral blood mononuclear cells (PBMC). Overexpression of TRPV1 was observed in THP-1 (acute monocytic leukemia) and U266B1 (multiple myeloma, MM), but not U937 (histiocytic lymphoma) compared to healthy PBMC. TRPV1 was also detected in all 49 patients (including B-cell non-Hodgkin’s lymphoma (B-NHL), MM and others, and 20 healthy controls. TRPV1 expression was increased in 8% of patients (MM=2, B-NHL=2). In conclusion, we provide an optimized flow cytometry method for routine expression analysis of clinical samples and show that TRPV1 is increased in 8% of patients with hematological malignancies.
Physiological pattern of cognitive aging
Authors: Novotný Jan S. , Gonzalez-Rivas Juan P. , Vassilaki Maria , Krell-Roesch Janina , Geda Yonas E. , Stokin Gorazd B.
Published: August 2021

The effect of aging on cognition in cognitively healthy adult populations remains poorly investigated. Given that cognition evolves in time and thus, during aging, and becomes eroded in several disorders, some of which have recently acquired biological definitions, it is imperative to understand the process of cognitive aging. To determine the association of aging with cognitive performance in a cognitively healthy population, we studied cognitive performance in population-based cohort of 673 adults (aged 25-89). We found a gradual decline in cognitive performance across the lifespan, which requires two decades to demonstate significant change. This age-related decline was not significantly altered by either gender or education. These findings contribute to understand cognitive aging and provide essential data on physiological cognition for more precise diagnostics and timely intervention of early changes in cognition.