Phase I trial of dose escalation for preoperative stereotactic radiosurgery for patients with large brain metastases.

BACKGROUND: Single session stereotactic radiosurgery (SRS) or surgical resection alone for brain metastases larger than 2 cm results in unsatisfactory local control. We conducted a phase I trial for brain metastases(>2cm) to determine the safety of preoperative SRS at escalating doses. METHODS: Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy for >4-6 cm. Dose limiting toxicity (DLT) was defined as grade III or greater acute toxicity. RESULTS: A total of 35 patients/36 lesions were enrolled. For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 Gy and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4 cm arm at 21Gy. The maximum tolerated dose (MTD) of SRS for >2-3 cm was not reached; and was 18 Gy for both >3-4 cm arm and >4-6 cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%. CONCLUSION: Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses.

Predictive analytics for cardiovascular patient readmission and mortality: An explainable approach.

BACKGROUND: Cardiovascular patients experience high rates of adverse outcomes following discharge from hospital, which may be preventable through early identification and targeted action. This study aimed to investigate the effectiveness and explainability of machine learning algorithms in predicting unplanned readmission and death in cardiovascular patients at 30 days and 180 days from discharge. METHODS: Gradient boosting machines were trained and evaluated using data from hospital electronic medical records linked to hospital administrative and mortality data for 39,255 patients admitted to four hospitals in New South Wales, Australia between 2017 and 2021. Sociodemographic variables, admission history, and clinical information were used as potential predictors. The performance was compared to LASSO regression, as well as the HOSPITAL and LACE risk score indices. Important risk factors identified by the gradient-boosting machine model were explored using Shapley values. RESULTS: The models performed well, especially for the mortality outcomes. Area under the receiver operating characteristic curve values were 0.70 for readmission and 0.87-0.90 for mortality using the full gradient boosting machine algorithms. Among the top predictors for 30-day and 180-day readmission were increased red cell distribution width, old age (especially above 80 years), high measured troponin and urea levels, not being married or in a relationship, and low albumin levels. For mortality, these included increased red cell distribution width, old age (especially older than 70 years), high measured troponin and urea levels, high neutrophil and monocyte counts, and low eosinophil and lymphocyte counts. The Shapley values gave clear insight into the dynamics of decision-tree-based models. CONCLUSIONS: We demonstrated an explainable predictive algorithm to identify cardiovascular patients who are at high risk of readmission or death at discharge from the hospital and identified key risk factors.

Cross-neutralizing antibody against emerging Omicron subvariants of SARS-CoV-2 in infection-naïve individuals with homologous BNT162b2 or BNT162b2(WT + BA.4/5) bivalent booster vaccination.

Since the emergence of SARS-CoV-2, different variants and subvariants successively emerged to dominate global virus circulation as a result of immune evasion, replication fitness or both. COVID-19 vaccines continue to be updated in response to the emergence of antigenically divergent viruses, the first being the bivalent RNA vaccines that encodes for both the Wuhan-like and Omicron BA.5 subvariant spike proteins. Repeated infections and vaccine breakthrough infections have led to complex immune landscapes in populations making it increasingly difficult to assess the intrinsic neutralizing antibody responses elicited by the vaccines. Hong Kong's intensive COVID-19 containment policy through 2020-2021 permitted us to identify sera from a small number of infection-naïve individuals who received 3 doses of the RNA BNT162b2 vaccine encoding the Wuhan-like spike (WT) and were boosted with a fourth dose of the WT vaccine or the bivalent WT and BA.4/5 spike (WT + BA.4/5). While neutralizing antibody to wild-type virus was comparable in both vaccine groups, BNT162b2 (WT + BA.4/BA.5) bivalent vaccine elicited significantly higher plaque neutralizing antibodies to Omicron subvariants BA.5, XBB.1.5, XBB.1.16, XBB.1.9.1, XBB.2.3.2, EG.5.1, HK.3, BA.2.86 and JN.1, compared to BNT162b2 monovalent vaccine. The single amino acid substitution that differentiates the spike of JN.1 from BA.2.86 resulted in a profound antigenic change.

Primary Non-Function of Hepatic Allograft With Preexisting Microvesicular Steatosis/Foamy Degeneration and Mild Large-Droplet Macrovesicular Steatosis.

It has been established that more than mild large-droplet macrovesicular steatosis (LD-MAS) is associated with increased risk of graft non-function. In contrast, even severe small-droplet macrovesicular steatosis (SD-MAS) has been found to be less prognostically significant. It remains unclear if a donor liver with diffuse microvesicular steatosis is associated with an increased risk of graft dysfunction. A 56-year-old male with alcoholic cirrhosis was transplanted with a liver from a 42-year-old overweight male donor after brain death. The frozen section of the donor liver biopsy taken at harvest showed diffusely enlarged clear/foamy hepatocytes and mild LD-MAS (about 5-10% of total tissue). The reperfusion liver biopsy taken at time 0 of transplantation showed hemorrhage, pale and enlarged hepatocytes, and mild LD-MAS (about 10% of total tissue) with lipopeliosis. The graft became non-functional, and the patient was re-transplanted 24 h after the initial transplantation. Histologic examination of the failed liver allograft showed extensive hemorrhagic necrosis, neutrophilic inflammation, diffuse microvesicular steatosis, and large extracellular fat droplets (about 20% of total tissue). This case demonstrates that precautions are needed to avoid using livers with diffuse and severe microvesicular steatosis.

Normothermic machine perfusion for liver transplantation: current state and future directions.

PURPOSE OF REVIEW: The number of patients on the liver transplant waitlist continues to grow and far exceeds the number of livers available for transplantation. Normothermic machine perfusion (NMP) allows for ex-vivo perfusion under physiologic conditions with the potential to significantly increase organ yield and expand the donor pool. RECENT FINDINGS: Several studies have found increased utilization of donation after cardiac death and extended criteria brain-dead donor livers with implementation of NMP, largely due to the ability to perform viability testing during machine perfusion. Recently, proposed viability criteria include lactate clearance, maintenance of perfusate pH more than 7.2, ALT less than 6000 u/l, evidence of glucose metabolism and bile production. Optimization of liver grafts during NMP is an active area of research and includes interventions for defatting steatotic livers, preventing ischemic cholangiopathy and rejection, and minimizing ischemia reperfusion injury. SUMMARY: NMP has resulted in increased organ utilization from marginal donors with acceptable outcomes. The added flexibility of prolonged organ storage times has the potential to improve time constraints and transplant logistics. Further research to determine ideal viability criteria and investigate ways to optimize marginal and otherwise nontransplantable liver grafts during NMP is warranted.

LncRNA LUCAT1 Promotes Glioblastoma Progression by Enhancing HIF1α Activity.

BACKGROUND: Hypoxia is associated with poor prognosis in many cancers including glioblastoma (GBM). Glioma stem-like cells (GSCs) often reside in hypoxic regions and serve as reservoirs for disease progression. Long non-coding RNAs (lncRNAs) have been implicated in GBM. However, the lncRNAs that modulate GSC adaptations to hypoxia are poorly understood. Identification of these lncRNAs may provide new therapeutic strategies to target GSCs under hypoxia. METHODS: lncRNAs induced by hypoxia in GSCs were identified by RNAseq. LUCAT1 expression was assessed by qPCR, RNAseq, Northern blot, single molecule FISH in GSCs, and interrogated in IvyGAP, TCGA, and CGGA databases. LUCAT1 was depleted by shRNA, CRISPR/Cas9, and CRISPR/Cas13d. RNAseq, Western blot, immunohistochemistry, co-IP, ChIP, ChIPseq, RNA immunoprecipitation, and proximity ligation assay were performed to investigate mechanisms of action of LUCAT1. GSC viability, limiting dilution assay, and tumorigenic potential in orthotopic GBM xenograft models were performed to assess the functional consequences of depleting LUCAT1. RESULTS: A new isoform of Lucat1 is induced by HIF1α and NRF2 in GSCs under hypoxia. LUCAT1 is highly expressed in hypoxic regions in GBM. Mechanistically, LUCAT1 formed a complex with HIF1α and its co-activator CBP to regulate HIF1α target gene expression and GSC adaptation to hypoxia. Depletion of LUCAT1 impaired GSC self-renewal. Silencing LUCAT1 decreased tumor growth and prolonged mouse survival in GBM xenograft models. CONCLUSIONS: A HIF1α-LUCAT1 axis forms a positive feedback loop to amplify HIF1α signaling in GSCs under hypoxia. LUCAT1 promotes GSC self-renewal and GBM tumor growth. LUCAT1 is a potential therapeutic target in GBM.

Improving Pediatric Fellows' Feedback Skills and Confidence Through Objective Structured Examinations.

Background Medical trainees must learn how to provide effective feedback as an essential communication skill, yet few models exist for training and assessing these skills. Objective To develop an observed structured feedback examination (OSFE) to provide feedback training to pediatric fellows and assess changes in skills and self-reported confidence. Methods This educational study was conducted from 2019 to 2020 at an academic children's hospital. Our team developed the OSFE and trained standardized feedback recipients and faculty. Fellows completed baseline self-assessments (31 items) on prior exposure to feedback training, application of skills, and confidence. They then participated in the OSFE, giving feedback to a standardized recipient using a standardized scenario, and were scored by faculty and recipients using a 15-item checklist for performance. Next, fellows participated in feedback training and received individualized feedback, after which they repeated the OSFE and confidence self-assessment. Three months later, fellows completed self-assessments on confidence and application of skills and another OSFE to assess retention. Descriptive statistics and signed rank sum test were used for analysis. Results Of 60 eligible fellows, 19 participated (32%), with 100% follow-up. After training and individualized feedback, all fellows improved feedback skills as measured by OSFE performance (mean change +0.89). All items, measured on a 5-point Likert scale, were sustained 3 months later (mean change +0.92). All fellows reported improved confidence in feedback knowledge (mean change +2.07 post, +1.67 3 months post). Conclusions Feedback training using simulation and individualized feedback moderately improved fellows' performance, confidence, and 3-month retention of feedback skills.

Serological assays for differentiating natural COVID-19 infection from vaccine induced immunity.

BACKGROUND: Natural SARS-CoV-2 infection may elicit antibodies to a range of viral proteins including non-structural protein ORF8. RNA, adenovirus vectored and sub-unit vaccines expressing SARS-CoV-2 spike would be only expected to elicit S-antibodies and antibodies to distinct domains of nucleocapsid (N) protein may reliably differentiate infection from vaccine-elicited antibody. However, inactivated whole virus vaccines may potentially elicit antibody to wider range of viral proteins, including N protein. We hypothesized that antibody to ORF8 protein will discriminate natural infection from vaccination irrespective of vaccine type. METHODS: We optimized and validated the anti-ORF8 and anti-N C-terminal domain (NCTD) ELISA assays using sera from pre-pandemic, RT-PCR confirmed natural infection sera and BNT162b2 (BNT) or CoronaVac vaccinees. We then applied these optimized assays to a cohort of blood donor sera collected in April-July 2022 with known vaccination and self-reported infection status. RESULTS: We optimized cut-off values for the anti-ORF8 and anti-N-CTD IgG ELISA assays using receiver-operating-characteristic (ROC) curves. The sensitivity of the anti-ORF8 and anti-N-CTD ELISA for detecting past infection was 83.2% and 99.3%, respectively. Specificity of anti-ORF8 ELISA was 96.8 % vs. the pre-pandemic cohort or 93% considering the pre-pandemic and vaccine cohorts together. The anti-N-CTD ELISA specificity of 98.9% in the pre-pandemic cohort, 93% in BNT vaccinated and only 4 % in CoronaVac vaccinated cohorts. Anti-N-CTD antibody was longer-lived than anti-ORF8 antibody after natural infection. CONCLUSIONS: Anti-N-CTD antibody assays provide good discrimination between natural infection and vaccination in BNT162b2 vaccinated individuals. Anti-ORF8 antibody can help discriminate infection from vaccination in either type of vaccine and help estimate infection attack rates (IAR) in communities.

nSEA: n-Node Subnetwork Enumeration Algorithm Identifies Lower Grade Glioma Subtypes with Altered Subnetworks and Distinct Prognostics.

Advances in molecular characterization have reshaped our understanding of low-grade glioma (LGG) subtypes, emphasizing the need for comprehensive classification beyond histology. Lever-aging this, we present a novel approach, network-based Subnetwork Enumeration, and Analysis (nSEA), to identify distinct LGG patient groups based on dysregulated molecular pathways. Using gene expression profiles from 516 patients and a protein-protein interaction network we generated 25 million sub-networks. Through our unsupervised bottom-up approach, we selected 92 subnetworks that categorized LGG patients into five groups. Notably, a new LGG patient group with a lack of mutations in EGFR, NF1, and PTEN emerged as a previously unidentified patient subgroup with unique clinical features and subnetwork states. Validation of the patient groups on an independent dataset demonstrated the robustness of our approach and revealed consistent survival traits across different patient populations. This study offers a comprehensive molecular classification of LGG, providing insights beyond traditional genetic markers. By integrating network analysis with patient clustering, we unveil a previously overlooked patient subgroup with potential implications for prognosis and treatment strategies. Our approach sheds light on the synergistic nature of driver genes and highlights the biological relevance of the identified subnetworks. With broad implications for glioma research, our findings pave the way for further investigations into the mechanistic underpinnings of LGG subtypes and their clinical relevance.Availability: Source code and supplementary data are available at https://github.com/bebeklab/nSEA.

Downstaging Hepatocellular Carcinoma before Transplantation: Role of Immunotherapy Versus Locoregional Approaches.

Hepatocellular carcinoma (HCC) continues to be a leading cause of cancer-related death in the United States. With advances in locoregional therapy for unresectable HCC during the last 2 decades and the recent expansion of transplant criteria for HCC, as well as ongoing organ shortages, patients are spending more time on the waitlist, which has resulted in an increased usage of locoregional therapies. The plethora of molecularly targeted therapies and immune checkpoint inhibitors under investigation represent the new horizon of treatment of HCC not only in advanced stages but also potentially at every stage of diagnosis and management.

Correction: Detection of novel coronaviruses in bats in Myanmar.

[This corrects the article DOI: 10.1371/journal.pone.0230802.].

Mitral annular disjunction in surgical mitral valve prolapse: prevalence, characteristics and outcomes.

BACKGROUND: There is a paucity of literature regarding outcomes of patients with mitral valve prolapse (MVP) and mitral annular disjunction (MAD) after mitral surgery, with many unanswered questions including the post-surgical persistence of MAD, effect of MAD on mitral valve reparability, and incidence of arrhythmia after mitral valve surgery. We aimed to examine the prevalence, imaging characteristics and clinical associations of mitral annular disjunction among patients undergoing mitral valve surgery for mitral valve prolapse, as well as outcomes after surgery including the persistence of MAD, arrhythmic events and excess mortality. RESULTS: A retrospective analysis of 111 consecutive patients who underwent mitral valve surgery for MVP was performed. A total of 32 patients (28.8%) had MAD. Patients with MAD were younger (64 vs 67 yrs, p = 0.04), with lower rates of hypertension (21.9% vs 50.6%, p = 0.01) and hyperlipidaemia (25% vs 50.6%; p = 0.01) and were more likely to be female (43.8% vs 21.4%, p = 0.04) with myxomatous leaflets > 5mm (90.6% vs 15.2%, p = < 0.01) and bileaflet prolapse (31.3% vs 10.1%, p = 0.02). Mitral valve repair was performed in 29/32 patients (90.6%) in the MAD positive group, and no patients had the persistence of MAD post-surgery. Post-operative ventricular arrhythmia was higher in the MAD positive group (28.13% vs 11.69%, p = 0.04) with no difference in mortality, 30-day hospital re-admission, or post-operative mitral regurgitation between patients with and without MAD over 3.91 years of follow up. CONCLUSION: In this study of consecutive patients with MVP undergoing surgery, MAD was a common finding (almost 1 in 3). MAD does not compromise mitral valve surgical reparability, and both repair and replacement are effective at correcting disjunction. Our data suggest that concurrent MAD in MVP patients undergoing surgery has no significant effect on post surgical outcomes. Further research as to whether this patient cohort requires post-surgical arrhythmia monitoring is warranted.

Tumor cell-derived spermidine promotes a pro-tumorigenic immune microenvironment in glioblastoma via CD8+ T cell inhibition.

The glioblastoma microenvironment is enriched in immunosuppressive factors that potently interfere with the function of cytotoxic T lymphocytes. Cancer cells can directly impact the immune system, but the mechanisms driving these interactions are not completely clear. Here we demonstrate that the polyamine metabolite spermidine is elevated in the glioblastoma tumor microenvironment. Exogenous administration of spermidine drives tumor aggressiveness in an immune-dependent manner in pre-clinical mouse models via reduction of CD8+ T cell frequency and phenotype. Knockdown of ornithine decarboxylase, the rate-limiting enzyme in spermidine synthesis, did not impact cancer cell growth in vitro but did result in extended survival. Furthermore, glioblastoma patients with a more favorable outcome had a significant reduction in spermidine compared to patients with a poor prognosis. Our results demonstrate that spermidine functions as a cancer cell-derived metabolite that drives tumor progression by reducing CD8+T cell number and function.

The impact of a dedicated operating room team on robotic transplant program growth and fellowship training.

INTRODUCTION: Despite considerable interest in robotic surgery, successful incorporation of robotics into transplant programs has been challenging. Lack of a dedicated OR team with expertise in both robotics and transplant is felt to be a major barrier. This paper assesses the impact of a dedicated robotic transplant team (DART) on program growth and fellowship training at one of the largest robotic transplant programs in North America. METHODS: This is a single center, retrospective review of all robotic operations performed on the transplant surgery service from October 2017 to October 2022. DART was incorporated in February 2020 and included transplant first assists (RFAs), scrub technologists and circulating nurses who received robotic training. Robotic experience before and after DART was compared to assess its impact on program growth and training. RESULTS: Four hundred and two robotic cases were performed by five transplant surgeons: 63 pre-DART and 339 post-DART. 40% of cases were transplant-related and 59.5%, HPB. There was a significant increase in case volume (2.5-10.6 cases/month, p < .0001) and complexity (36.5% vs. 70.3% high complexity cases, p < .0001) post-DART. RFA case coverage increased from 17% to 95%, and participation of transplant fellows as primary surgeons increased from 17% to 95% post-DART period (both p < .05). Conversion rates (9.5% vs. 4.1%) and room turn-around-times (TAT) (58.4 vs. 40.3 min) were lower post-DART (p < .05). There were no emergent conversions, conversions in transplant patients, or robot-related complications in either group. CONCLUSION: OR teams with expertise in robotics and transplant surgery can accelerate growth of robotic transplant programs while maintaining patient safety.

Haustral rhythmic motor patterns of the human large bowel revealed by ultrasound.

Effective and widely available strategies are needed to diagnose colonic motility dysfunction. We investigated whether ultrasonography could generate spatiotemporal maps combined with motor pattern frequency analysis, to become a noninvasive method to characterize human colon motor patterns. Abdominal colonic ultrasonography was performed on healthy subjects (N = 7), focusing on the detailed recording of spontaneous haustral activities. We developed image segmentation and frequency analysis software to analyze the motor patterns captured. Ultrasonography recordings of the ascending, transverse, and descending colon identified three distinct rhythmic motor patterns: the 1 cycle/min and the 3 cycles/min cyclic motor pattern were seen throughout the whole colon, whereas the 12 cycles/min cyclic motor pattern was identified in the ascending colon. The rhythmic motor patterns of the human colon that are associated with interstitial cells of Cajal-associated pacemaking activity can be accurately identified and quantified using ultrasound.NEW & NOTEWORTHY Ultrasonography in the clinical field is an underutilized tool for assessing colonic motility; however, with the addition of frequency analysis techniques, it provides a method to identify human colonic motor patterns. Here we report on the 1, 3, and 12 cpm rhythmic motor patterns. Ultrasound has the potential to become a bedside assessment for colonic dysmotility and may reveal the health of interstitial cells of Cajal (ICC) pacemaker activities.

Robotic donor nephrectomy: optimizing outcomes beyond the limitations of laparoscopy.

BACKGROUND: Robotic donor nephrectomy (RDN) has emerged as a safe alternate to laparoscopic donor nephrectomy (LDN), offering improved visualization, instrument dexterity and ergonomics. There is still concern about how to safely transition from LDN to RDN. METHODS: We performed a retrospective review of 150 consecutive living donor operations (75 LDN and 75 RDN) at our center, comparing the first 75 RDN's with the last 75 LDN's performed prior to the initiation of the robotic transplant program. Operative times and complications were used as surrogates of efficiency and safety, respectively, to estimate the learning curve with RDN. RESULTS: RDN was associated with a longer total operative time (RDN 182 vs LDN 144 min; P < 0.0001) but a significantly shorter post-operative length of stay (RDN 1.8 vs LDN 2.1 days; P = 0.0213). Donor complications and recipient outcomes were the same between both groups. Learning curve of RDN was estimated to be about 30 cases. CONCLUSIONS: RDN is a safe alternate to LDN with acceptable donor morbidity and no negative impact on recipient outcomes even during the early part of the RDN learning curve. Surgeon preferences for the robotic approach compared to traditional laparoscopy will require further scrutiny to improve ergonomics and operative efficiency.

AIR SAC TREMATODES (CYCLOCOELIDAE STOSSICH, 1902) INFECTING BIRDS IN ZOOLOGICAL INSTITUTIONS IN THE UNITED STATES.

Air sac trematodes (Digenea: Cyclocoelidae) were detected in 23 avian species from eight aviaries in the United States. Most of the infected host species were passeriform birds, but a few species in other orders also were infected. Four species of adult flukes were encountered: Circumvitellatrema momota, Morishitium sp., Psophiatrema greineri, and Szidatitrema yamagutii. Findings from retrospective review of medical records, necropsy records, and author observations are presented. Potential terrestrial snail intermediate hosts were collected from three indoor aviaries. A high prevalence (47%) of larval trematode infections was demonstrated in one species of nonnative snail (Prosopeas achatinacea); one larva was isolated and matched to the adult species (C. momota) from birds using PCR. Problems with introducing potentially infected wild-caught birds into aviaries, and exchanging captive individuals between aviaries where they potentially may carry infections, are discussed.

18F-fluciclovine PET/CT to distinguish radiation necrosis from tumor progression for brain metastases treated with radiosurgery: results of a prospective pilot study.

PURPOSE: Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions. METHODS: Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation. RESULTS: Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUVmax statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUVmean (AUC = 0.875; p = 0.018), SUVpeak (AUC = 0.813; p = 0.007), and SUVpeak-to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUVmax-to-normal-brain (p = 0.1) and SUVmean-to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2). CONCLUSIONS: In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance.