Faculty Bibliography

Soon after the World Health Organization declared the severe acute respiratory syndrome coronavirus 2 a global health emergency on January 30, 2020, New York City was plagued by the virus and its health system and economy pushed to their limits. The majority of the limited neurosurgical data in relation to COVID-19 is anecdotal and the higher theoretical risk of transmission of the virus among skull base aerosol generating (SBAG) cases has not been investigated or discussed in a neurosurgical population. We discuss a series of 13 patients who underwent 15 SBAG surgical procedures during the peak of COVID-19 in our hospital system and the protocols use perioperatively for their procedures. Our data support that with proper preoperative testing, a well-delineated surgical algorithm, and appropriate personal protective equipment, emergent/urgent cases can be done safely in hospitals that are currently experiencing high volumes of COVID-19 cases as we did in March to May of 2020.

OBJECTIVES/UNASSIGNED:Data on the efficacy of including definitive local therapy to the primary site for head and neck squamous cell carcinoma (HNSCC) patients with synchronous distant metastasis are lacking. In multiple different solid tumor types, there has been benefit when using systemic therapy followed by local consolidative therapy (stereotactic ablative radiotherapy or surgery) directed at metastases. We proposed to retrospectively evaluate patients at our institution that received definitive treatment to the primary. METHODS/UNASSIGNED:Single institution retrospective study evaluating 40 patients with metastatic HNSCC treated with definitive surgery (55%) or chemoradiation (45%) to the primary site from 2000 to 2020. The major endpoints were overall survival (OS) and progression-free survival (PFS) for the total population and multiple sub-groups. Some variables were evaluated with multiple covariates Cox model. RESULTS/UNASSIGNED:The median PFS was 8.6 months (95% CI, 6.4-11.6), and OS was 14.2 months (95% CI, 10.9-27.5). In 28% of patients that received induction therapy, there was a twofold increase in median overall survival to 27.5 months. In the 33% of patients that received anti-PD-1 mAb as part of their treatment course, the median OS was significantly increased to 41.7 months (95% CI, 8.7-NR) versus 12.1 months (95% CI, 8.4-14.4) with a 5-year OS of 39%. Multivariate analysis for OS showed significance for age at diagnosis, use of IO, and number of metastatic sites. CONCLUSION/UNASSIGNED:We observed impressive survival outcomes in metastatic HNSCC patients treated with definitive local therapy to the primary site in addition to induction and/or immunotherapy. Further study is warranted.Level of Evidence: 3.

Surgical proctoring requires increasing resources in growing healthcare systems. In addition, travel has become less safe in the era of COVID-19. This study demonstrates surgeon satisfaction and safety with tele-proctoring in robotic gynecologic surgery. This pilot study assesses surgeon satisfaction and operative outcomes with a novel operative tele-proctoring system with a continuous two-way video-audio feed that allows the off-site surgeon to see the operating room, surgical field, and hands of the robotic surgeon. After thorough system testing, two experienced surgeons underwent tele-proctoring for hospital credentialing, completing 7 total cases. Each completed pre- and post-surveys developed from the Michigan Standard Simulation Experience Scale. Surgical characteristics were compared between tele-proctored cases and 59 historical cases proctored in-person over the last 8 years. Surgeons reported unanimous high satisfaction with tele-proctoring (5 ± 0). There were no major technologic issues. Five of the tele-proctored cases and 35 of controls were hysterectomies. Mean age was 48.2 ± 1.4 years, mean BMI was 29.6 ± 0.9 kg/m², and mean uterine weight was 152 ± 112.3 g. Two-thirds had prior abdominal surgery (P > 0.1). Tele-proctored hysterectomies were 58 ± 6.5 min shorter than controls (P = 0.001). There were no differences in EBL or complication rates (P > 0.1). Tele-proctoring resulted in high surgeon satisfaction rates with no difference in EBL or complications. Tele-mentoring is a natural extension of tele-proctoring that could provide advanced surgical expertise far beyond where we can physically reach.

PURPOSE: The prognosis for SHH-medulloblastoma (MB) patients with Li-Fraumeni syndrome (LFS) is poor. Due to lack of comprehensive data for these patients, it is challenging to establish effective therapeutic recommendations. We here describe the largest retrospective cohort of pediatric LFS SHH-MB patients to date and their clinical outcomes.
PATIENTS AND METHODS: N=31 patients with LFS SHH-MB were included in this retrospective multicenter study. TP53 variant type, clinical parameters including treatment modalities, event-free survival (EFS) and overall survival (OS), as well as recurrence patterns and incidence of secondary neoplasms, were evaluated.
RESULT(S): All LFS-MBs were classified as SHH subgroup, in 30/31 cases based on DNA methylation analysis. The majority of constitutional TP53 variants (72%) represented missense variants, and all except two truncating variants were located within the DNA-binding domain. 54% were large cell anaplastic, 69% gross totally resected and 81% had M0 status. The 2-(y)ear and 5-(y)ear EFS were 26% and 8,8%, respectively, and 2y- and 5y-OS 40% and 12%. Patients who received post-operative radiotherapy (RT) followed by chemotherapy (CT) showed significantly better outcomes (2y-EFS:43%) compared to patients who received CT before RT (30%) (p<0.05). The 2y-EFS and 2y-OS were similar when treated with protocols including high-dose chemotherapy (EFS:22%, OS:44%) compared to patients treated with maintenance-type chemotherapy (EFS:31%, OS:45%). Recurrence occurred in 73.3% of cases independent of resection or M-status, typically within the radiation field (75% of RT-treated patients). Secondary malignancies developed in 12.5% and were cause of death in all affected patients.
CONCLUSION(S): Patients with LFS-MBs have a dismal prognosis. This retrospective study suggests that upfront RT may increase EFS, while intensive therapeutic approaches including high-dose chemotherapy did not translate into increased survival of this patient group. To improve outcomes of LFS-MB patients, prospective collection of clinical data and development of treatment guidelines are required

Image-guided interventional techniques have emerged as promising treatments for thyroid disease. Percutaneous ethanol ablation, radiofrequency ablation, laser ablation, high intensity focused ultrasound, and microwave ablation have shown efficacy in treating benign thyroid disease. There is increasing evidence that these techniques may effectively treat papillary thyroid microcarcinomas, recurrent and metastatic disease, follicular neoplasms, and parathyroid lesions. They are performed in an outpatient setting, well-tolerated, with negligible risk for thyroid hormone supplementation, making them a popular alternative to surgical resection. In this comprehensive review, we discuss the devices, techniques, advantages, and disadvantages of each intervention, and summarize the published outcomes.

BACKGROUND/UNASSIGNED:Much has been written about the diagnosis and treatment of soft tissue mallet injuries. However, there has been little regarding the characteristics of this injury affecting patients' prognosis. The purpose of this prospective study was to identify factors influencing the outcome of treatment of soft tissue mallet injuries. METHODS/UNASSIGNED:12 months. RESULTS/UNASSIGNED:15°. Those failing splint treatment were older compared with those successfully treated. Patient compliance was significantly associated with a successful outcome. Factors that did not significantly affect success included time to treatment, initial injury severity, splinting duration, sex, and ligamentous laxity. Disabilities of Arm, Shoulder, and Hand scores >0 were not associated with treatment failure. Radiographic and clinical extension lag were statistically comparable. CONCLUSIONS/UNASSIGNED:This study shows strong association between the success of splint treatment, younger patient age, and compliance with the treatment protocol. Despite this finding, most patients did not report any functional limitations, irrespective of the treatment success. In contrast to prior results, time to treatment and initial extensor lag did not significantly affect treatment success.

Elevated neural plasticity during development contributes to dramatic improvements in perceptual, motor, and cognitive skills. However, malleable neural circuits are vulnerable to environmental influences that may disrupt behavioral maturation. While these risks are well-established prior to sexual maturity (i.e., critical periods), the degree of neural vulnerability during adolescence remains uncertain. Here, we induce transient hearing loss (HL) spanning adolescence in gerbils, and ask whether behavioral and neural maturation are disrupted. We find that adolescent HL causes a significant perceptual deficit that can be attributed to degraded auditory cortex processing, as assessed with wireless single neuron recordings and within-session population-level analyses. Finally, auditory cortex brain slices from adolescent HL animals reveal synaptic deficits that are distinct from those typically observed after critical period deprivation. Taken together, these results show that diminished adolescent sensory experience can cause long-lasting behavioral deficits that originate, in part, from a dysfunctional cortical circuit.

BACKGROUND/UNASSIGNED:hybridization (FISH) and microbial community profiling (MCP) are methods of studying microbial environments of explanted devices that can provide information to reduce morbidity and costs of infected CIs. AIMS/OBJECTIVES/UNASSIGNED:To describe the results and clinical significance of bacterial analyses conducted on explanted CIs. MATERIAL AND METHODS/UNASSIGNED:Between 2013 and 2017, 12 explanted devices underwent microbiological analysis in addition to the manufacturer's device failure analysis. Patients' clinical history, infection status and outcome were reviewed and correlated with microbial analysis results. RESULTS/UNASSIGNED:From 2013 to 2017, 12 Cochlearâ„¢ devices from 11 patients underwent additional MCP or FISH analysis. Five devices were explanted due to suspected implant associated infection, and seven were explanted for other reasons. FISH analysis revealed biofilm presence on all infected devices, only partial correlation of cultures with biofilm composition and confirmation that biofilm formation occurs preferentially at particular device interfaces and geometries. MCP analysis presented challenges in data analysis inherent to its technique but correlated with cultures of infected devices and suggested a diverse microbial composition of explanted devices. CONCLUSIONS AND SIGNIFICANCE/UNASSIGNED:Microbial analysis of explanted devices can aid in further elucidating treatment approaches to infected CIs.

The goal of therapy for essential thrombocythemia (ET) and polycythemia vera (PV) patients is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for ET and PV patients at high-risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment naïve, high-risk ET/PV patients. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (p=0.80) at 12 months. At 24/36 months, CR was 20%/17% for HU and 29%/33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, while grade 3/4 adverse events were more frequent with PEG (46% vs. 28%). At 12 months of treatment there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment PEG was more effective in normalizing blood counts and reducing driver mutation burden, while HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk ET/PV patients. (Funded by the National Cancer Institute, 5P01CA108671-09; clinicaltrials.gov number (NCT01259856).

In phase I development, CDX-3379, an anti-ErbB3 monoclonal antibody, showed promising molecular and antitumor activity in head and neck squamous cell carcinoma (HNSCC), alone or in combination with cetuximab. Preliminary biomarker data raised the hypothesis of enhanced response in tumors harboring FAT1 mutations. This phase II, multicenter trial used a Simon 2-stage design to investigate the efficacy of CDX-3379 and cetuximab in 30 patients with recurrent/metastatic, HPV-negative, cetuximab-resistant HNSCC. The primary endpoint was objective response rate (ORR). Secondary endpoints included ORR in patients with somatic FAT1 mutations, progression-free survival (PFS), overall survival (OS), and safety. Thirty patients were enrolled from March 2018 to September 2020. The ORR in genomically unselected patients was 2/30 (6.7%; 95% confidence interval [CI], 0.8-22.1). Median PFS and OS were 2.2 (95% CI: 1.3-3.6) and 6.6 months (95% CI: 2.7-7.5), respectively. Tissue was available in 27 patients including one of two responders. ORR was 1/10 (complete response; 10%; 95% CI 0.30-44.5) in the FAT1-mutated versus 0/17 (0%; 95% CI: 0-19.5) in the FAT1-wildtype cohorts. Sixteen patients (53%) experienced treatment-related adverse events (AEs) ≥ grade 3. The most common AEs were diarrhea (83%) and acneiform dermatitis (53%). Dose modification was required in 21 patients (70%). The modest ORR coupled with excessive, dose-limiting toxicity of this combination precludes further clinical development. Dual ErbB3-EGFR inhibition remains of scientific interest in HPV-negative HNSCC. Should more tolerable combinations be identified, development in an earlier line of therapy and prospective evaluation of the FAT1 hypothesis warrant consideration.