Nutritional Status as a Predictive Biomarker for Immunotherapy Outcomes in Advanced Head and Neck Cancer

The association between pretreatment nutritional status and immunotherapy response in patients with advanced head and neck cancer is unclear. We retrospectively analyzed a cohort of 99 patients who underwent treatment with anti-PD-1 or anti-CTLA-4 antibodies (or both) for stage IV HNSCC between 2014 and 2020 at the Johns Hopkins Hospital. Patient demographics and clinical characteristics were retrieved from electronic medical records. Baseline prognostic nutritional index (PNI) scores and pretreatment body mass index (BMI) trends were calculated. Associations between PNI and BMI were correlated with overall survival (OS), progression-free survival (PFS), and immunotherapy response. In univariate analysis, there was a significant correlation between OS and PFS with baseline PNI (OS: HR: 0.464; 95% CI: 0.265–0.814; PFS: p = 0.007 and HR: 0.525; 95% CI: 0.341–0.808; p = 0.003). Poor OS was also associated with a greater decrease in pretreatment BMI trend (HR: 0.42; 95% CI: 0.229–0.77; p = 0.005). In multivariate analysis, baseline PNI but not BMI trend was significantly associated with OS and PFS (OS: log (HR) = −0.79, CI: −1.6, −0.03, p = 0.041; PFS: log (HR) = −0.78, CI: −1.4, −0.18, p = 0.011). In conclusion, poor pretreatment nutritional status is associated with negative post-immunotherapy outcomes.

294. Surveillance for Potential Post-Acute COVID-19 Syndrome Medical Complications in the Emergency Department (ED) – A Retrospective Longitudinal Study of ED Patients Who Had Evidence of SARS-CoV-2 Infection Versus Those Who Did Not

Background As the COVID-19 pandemic continues, growing attention has been placed on whether patients previously infected with SARS-CoV-2 have an increased risk of developing and/or exacerbating medical complications. Our study aimed to determine whether individuals with previous evidence of SARS-CoV-2 infection prior to their current emergency department (ED) visit were more likely to present with specific clinical sign/symptoms, laboratory markers, and/or clinical complications. Methods A COVID-19 seroprevalence study was conducted at Johns Hopkins Hospital ED (JHH ED) from March 16 to May 31, 2020. Evidence of ever having SARS-CoV-2 infection (PCR positive or IgG Ab positive) was found in 268 ED patients at this time (i.e. infected and/or previously infected). These patients were matched 1:2 to controls, by date, to other patients who attended the JHHED. Clinical signs/symptoms, laboratory markers, and/or clinical complications associated with ED visits and/or hospitalizations at JHH within 6 months after their initial ED visit was abstracted through chart review for these 804 patients. Cox proportional hazards regression analyses were performed. Results Among 804 ED patients analyzed, 50% were female, 56% Black race, and 15% Hispanic with a mean age of 47 years. 323 (40%) patients had at least 1 subsequent ED visit and additional 70 (9%) had been admitted to JHH. After controlling for race and ethnicity, patients with evidence of current or prior COVID-19 infection were more likely to require supplemental oxygen [hazards ratio (HR) =2.53; p=0.005] and have a cardiovascular complication [HR =2.13; p=0.008] during the subsequent ED visit than the non-infected patients. Conclusion Our findings demonstrate that those previously infected with SARS-CoV-2 have an increased frequency of cardiovascular complications and need for supplemental oxygen in ED visits in the months after their initial SARS-CoV-2 infection was detected. EDs could serve as a critical surveillance site for monitoring post-acute COVID-19 syndrome complications. Disclosures Richard E. Rothman, PhD, MD, Chem bio (Grant/Research Support)

Sedation and Analgesia in Patients Undergoing Tracheostomy in COVID-19, a Multi-Center Registry

Introduction Patients with COVID-19 ARDS require significant amounts of sedation and analgesic medications which can lead to longer hospital/ICU length of stay, delirium, and has been associated with increased mortality. Tracheostomy has been shown to decrease the amount of sedative, anxiolytic and analgesic medications given to patients. The goal of this study was to assess whether tracheostomy decreased sedation and analgesic medication usage, improved markers of activity level and cognitive function, and clinical outcomes in patients with COVID-19 ARDS. Study Design and Methods A retrospective registry of patients with COVID-19 ARDS who underwent tracheostomy creation at the University of Pennsylvania Health System or the Johns Hopkins Hospital from 3/2020 to 12/2020. Patients were grouped into the early (≤14 days, n = 31) or late (15 + days, n = 97) tracheostomy groups and outcome data collected. Results 128 patients had tracheostomies performed at a mean of 19.4 days, with 66% performed percutaneously at bedside. Mean hourly dose of fentanyl, midazolam, and propofol were all significantly reduced 48-h after tracheostomy: fentanyl (48-h pre-tracheostomy: 94.0 mcg/h, 48-h post-tracheostomy: 64.9 mcg/h, P = .000), midazolam (1.9 mg/h pre vs. 1.2 mg/h post, P = .0012), and propofol (23.3 mcg/kg/h pre vs. 8.4 mcg/kg/h post, P = .0121). There was a significant improvement in mobility score and Glasgow Coma Scale in the 48-h pre- and post-tracheostomy. Comparing the early and late groups, the mean fentanyl dose in the 48-h pre-tracheostomy was significantly higher in the late group than the early group (116.1 mcg/h vs. 35.6 mcg/h, P = .03). ICU length of stay was also shorter in the early group (37.0 vs. 46.2 days, P = .012). Interpretation This data supports a reduction in sedative and analgesic medications administered and improvement in cognitive and physical activity in the 48-h period post-tracheostomy in COVID-19 ARDS. Further, early tracheostomy may lead to significant reductions in intravenous opiate medication administration, and ICU LOS.

Brain and Muscle Metabolic Changes by FDG-PET in Stiff Person Syndrome Spectrum Disorders

Objective: To report clinical characteristics and fluorodeoxyglucose positron emission tomography (FDG-PET) findings in the brain and muscles of individuals with stiff person syndrome (SPS) spectrum disorders (SPSSDs).Methods: Retrospective cohort study from 1997 to 2018 at Johns Hopkins Hospital identified 170 individuals with SPS or cerebellar ataxia (CA) associated with anti-glutamic acid decarboxylase (anti-GAD)-65 antibodies. Fifty-one underwent FDG-PET, with 50 involving the body and 30 with dedicated brain acquisition. The clinical and immunological profiles were extracted via medical record review. The brain scans were analyzed quantitatively using the NeuroQ software, with comparison with an averaged normal database. The body scans were reviewed qualitatively by a blinded nuclear medicine radiologist.Results: Mean age of symptom onset was 41.5 years (range 12–75 years). Majority were female (68%) and White (64%). Of the patients, 82% had SPS (majority being classic phenotype), and 18% had CA. Three had a paraneoplastic process. Forty-seven had serum anti-GAD, two with anti-amphiphysin, and one with anti-glycine receptor antibodies. Brain metabolic abnormalities were seen in both SPS and CA, with significant differences between the groups noted in the right superior frontal cortex, right sensorimotor cortex, left inferior parietal cortex, bilateral thalami, vermis, and left cerebellum. Of the patients, 62% demonstrated muscle hypermetabolism, most commonly bilateral, involving the upper extremities or axial muscles. Neither brain nor muscle metabolism was correlated with functional outcomes nor treatments.Conclusions: Metabolic changes as seen by FDG-PET are present in the brain and muscle in many individuals with SPSSD. Future studies are needed to assess whether FDG-PET can help aid in the diagnosis and/or monitoring of individuals with SPSSD.

Ketogenic Diet Therapy for Epilepsy Associated With Aicardi Syndrome

Introduction: Aicardi syndrome is a rare neurodevelopmental disorder associated with epilepsy in females. Ketogenic diet therapy represents a possible nonpharmacologic treatment in Aicardi syndrome patients. Methods: All patients with Aicardi syndrome seen at Johns Hopkins Hospital (Baltimore, MD) and Johns Hopkins All Children’s Hospital (St Petersburg, FL) treated with ketogenic diet therapy since 1994 were evaluated retrospectively. Results: Fifteen patients, ages 4 months to 34 years, were identified. Ten (67%) patients experienced a ≥50% seizure reduction after 3 months, with 3 (20%) having a ≥90% reduction. Only 1 patient was seizure-free for a short period of time. The number of drugs tried prior to ketogenic diet therapy initiation was correlated with ≥50% seizure reduction at 3 months, 5.8 vs 2.6 in responders versus nonresponders ( P = .01). In addition, the mean number of drugs actively received also correlated, 3.0 vs 1.2, P = .005. Ketogenic diet therapy was slightly more successful in those without infantile spasms, 78% vs 50%, P = .33. Conclusion: Ketogenic diet therapy was helpful in Aicardi syndrome, although seizure freedom was rare. It was especially helpful for those who were more drug-resistant and did not have infantile spasms at ketogenic diet therapy onset.

ECOA-10. Integrated genomic and clinical analysis of BRAF-mutated glioma in adults

BRAF alterations are recognized as a significant driver of disease in pediatric low-grade glioma (pLGG) but the implications of BRAF alterations on the natural history and response to treatment are unclear in adult glioma. We characterized the molecular and clinical features of a multi-institutional cohort of adults with BRAF-mutated gliomas. We identified patients with glioma containing BRAF alterations on sequencing in multi-institutional cohorts (Dana-Farber/Brigham Cancer Center, Johns Hopkins Hospital, GENIE, TCGA). BRAF alterations were grouped into previously defined classes: I (V600E; RAS-independent/dimerization-independent), II (RAS-independent/dimerization-dependent), III (RAS-dependent/dimerization-dependent) in addition to BRAF copy number gains, fusions, and other. We interrogated 289 BRAF-altered gliomas (199 patients >=18yrs, 90 patients <18yrs; range 0-85yrs), and observed histopathologic and molecular differences between BRAF-altered gliomas in adults versus pediatric patients. Amongst adults, the most common BRAF alterations were Class I followed by copy number gains, with glioblastoma (GBM) the most prevalent histology. In comparison, pediatric gliomas in our cohort frequently harbored Class I mutations followed by BRAF fusions, with primarily pilocytic astrocytoma and pLGG histologies. Principal component analysis and correlation analysis revealed molecular features associated with gliomas of different BRAF alterations and histologies, including mutation of NF1, a negative regulator of RAS, which was significantly associated with class II/III BRAF alterations (64.3%) and not observed in BRAFV600E-mutated gliomas (0%, n=62) (p<0.0001). Demographic and molecular features were evaluated for correlates for adult glioma risk stratification. Comparative survival analysis showed no significant difference between adult GBM harboring Class I compared to other BRAF alterations, whereas young adult age (18-35yrs) was associated with improved outcomes (p<0.05). Among 86 GBM patients with detailed clinicopathologic data, 7 received RAF-targeted therapy, with variable clinical response. This cohort of BRAF-altered adult gliomas demonstrates a broad range of molecular alterations with implications for treatment sensitivity and patient risk stratification.

Predictors of an academic career among fellowship-trained spinal neurosurgeons

OBJECTIVE Although fellowship training is becoming increasingly common in neurosurgery, it is unclear which factors predict an academic career trajectory among spinal neurosurgeons. In this study, the authors sought to identify predictors associated with academic career placement among fellowship-trained neurological spinal surgeons. METHODS Demographic data and bibliometric information on neurosurgeons who completed a residency program accredited by the Accreditation Council for Graduate Medical Education between 1983 and 2019 were gathered, and those who completed a spine fellowship were identified. Employment was denoted as academic if the hospital where a neurosurgeon worked was affiliated with a neurosurgical residency program; all other positions were denoted as nonacademic. A logistic regression model was used for multivariate statistical analysis. RESULTS A total of 376 fellowship-trained spinal neurosurgeons were identified, of whom 140 (37.2%) held academic positions. The top 5 programs that graduated the most fellows in the cohort were Cleveland Clinic, The Johns Hopkins Hospital, University of Miami, Barrow Neurological Institute, and Northwestern University. On multivariate analysis, increased protected research time during residency (OR 1.03, p = 0.044), a higher h-index during residency (OR 1.12, p < 0.001), completing more than one clinical fellowship (OR 2.16, p = 0.024), and attending any of the top 5 programs that graduated the most fellows (OR 2.01, p = 0.0069) were independently associated with an academic career trajectory. CONCLUSIONS Increased protected research time during residency, a higher h-index during residency, completing more than one clinical fellowship, and attending one of the 5 programs graduating the most fellowship-trained neurosurgical spinal surgeons independently predicted an academic career. These results may be useful in identifying and advising trainees interested in academic spine neurosurgery.