Exploding power: a statewide review of lithium battery related burns

Introduction: With the increase of lithium battery devices, including electronic cigarettes and battery power banks, there has been a steady rise in burn injuries secondary to device malfunction. These devices may cause chemical or flame burns. Our aim was to identify and classify epidemiological trends of explosions from lithium battery devices across the state of New South Wales (NSW), Australia. Methods: A review of the NSW Burn Injury Service (SBIS) database from January 2005–December2019, together with medical records from the burns units at the Children’s Hospital at Westmead (CHW), the Concord Repatriation General Hospital (CRGH) and the Royal North Shore Hospital (RNSH) was conducted. All patients who suffered a burn secondary from a lithium battery device were included and data was extracted on mechanism of injury, severity of injury and management. This study was approved by the ethics committees of CHW, RNSH and CRGH [2020/PID00179]. Results: Of the 24 patients identified, six were paediatric and 18 were adults. The majority were male (7:1) with a mean age of 29.0 (+/- 16.6 years). The mean total body surface area burnt was 2.5% (+/- 0.9) [range 0.1–21.0%]. The majority occurred after 2014 and involved spontaneous explosions. Their injuries ranged from partial to full thickness burns with flame being the most common type (n=15). Three quarters of the cases (n=18) occurred in a home setting. Conclusions: Lithium battery device explosions can result in a mix of burn depth injuries from flame, contact and electrical, or chemical burns. Consumers need to be made more aware of the potential risks associated with use of lithium battery powered devices.

The Impact of COVID-19 on Hand Trauma

Background The Coronavirus Disease 2019 (COVID-19) pandemic has had a dramatic impact on individual and societal behaviors, as well as on health care systems. It confers a unique opportunity to examine the relationship among disease, policies, and patterns of activity, as well as their impacts on surgical unit functionality. This study aims to compare the distribution and patterns of injury at a tertiary hand surgery trauma center before and during the COVID-19 pandemic. Methods A retrospective analysis of all patients presenting to the Royal North Shore Hospital hand surgery service in the 5-week period from March 16 to April 21 in 2019 and 2020 was undertaken, forming 2 cohorts for comparison. Demographic, injury, and operative data were collected and compared descriptively using comparative statistics. Results There were 114 primary operative presentations during the 5-week period in 2020, representing a 27.4% decrease from the 157 presentations during the equivalent period in 2019. There was an increase in the proportion of emergency presentations from 73.9% in 2019 to 85.1% in 2020 ( P = .03), with a corresponding decrease in elective presentations during 2020. The incidence of sporting injuries and motor vehicle accidents decreased in 2020, whereas falls and accidents involving knives and tools remained relatively constant. Operating times decreased in 2020, whereas the length of hospital stay remained constant. Conclusions The COVID-19 pandemic and consequent restrictions of activity have had substantial impacts on the patterns of hand trauma and its management. These insights have implications for staff and resource management during times of social disruption in the future.

PATH-18. A MULTI-CENTER CASE SERIES OF ADULT K27M MUTATED DIFFUSE MIDLINE GLIOMAS REVEALING A POPULATION UNIQUE FROM PAEDIATRIC CASES

BACKGROUND Histone mutations in the K27M gene were first described in 2014, and incorporated into the WHO CNS tumour classification system in 2016. They are typically associated with diffuse midline gliomas (DMG). Presenting symptoms vary greatly, with some experiencing significant delay in diagnosis. Median survival is only 9-12 months for these patients. Biopsy samples are small, and in some due to location, not performed. Although data is predominately based on the paediatric population, DMGs are seen in both adolescence and adults. In this multi-site retrospective study, we describe 11 adult patients with K27M DMG gliomas across two tertiary Neuro-Oncology services in Sydney, Australia. To the authors’ knowledge we present the largest known collection of adult K27M cases in the Asia-Pacific region with correlation of treatment, clinicopathologic and radiologic features with outcomes. METHODS The glioma databases of Royal North Shore Hospital (RNSH) and Royal Prince Alfred Hospital (RPAH) between January 2009 and March 2020 were interrogated to identify patients. Selection criteria included patients aged ≥ 18 years who presented with a DMG, had undergone biopsy, and had confirmed K27M via next generation sequencing. Clinicopathologic, radiologic and treatment outcomes were extracted for correlation. RESULTS Eleven patients fitting the selection criteria were identified and reported. The median age at diagnosis was 30 years and 4 were female. Five presented with hydrocephalus, the most common presenting symptoms were headaches and nausea and/or vomiting (n= 4 and n= 2 respectively). The median progression-free survival was 13 months (4-31 months) and the median overall survival was 23 months (4-59 months). CONCLUSION This case series reports the outcomes of older patients with K27M. The clinical course demonstrated suggests a divergence from paediatric biology. Ongoing studies are required to further characterise the histopathological and clinical differences of these tumours in older patients.

416 SQ3370–001 is a multi-center open-label phase I dose-escalation study to test a novel intratumoral and systemic approach to treat advanced solid tumors

BackgroundCancer immunotherapies have been very successful in recent times; however, they benefit only a subset of patients and have varying response rates across tumor types. Conversely, conventional chemotherapies are effective in a large group of patients, but have limited dosing capabilities, lack specificity, and often result in systemic adverse events. Here, we present SQ3370, a novel approach that activates doxorubicin (Dox) at the tumor site while avoiding systemic toxicities commonly associated with the therapy, and also potentially activates an immune response against tumors. SQ3370 is based on a local intratumoral injection of a prodrug-capturing biomaterial (SQL70) followed by 5 daily systemic infusions of an attenuated form of Dox (SQP33). Mutually-reactive click chemistry groups in the 2 components allow the capture and release of active Dox at the tumor site. While conventional Dox is known to induce immune activation1 and enhance tumor responsiveness to checkpoint inhibitors,2 its benefit is limited by cumulative dose cardiotoxicity. We safely administered SQ3370 in dogs at 8.95-times the veterinary clinical dose of Dox with minimal side effects including cardiotoxicity and immunosuppression. In syngeneic mouse models, SQ3370 improved overall survival and induced a robust anti-tumor response against the biomaterial-injected lesion compared to conventional Dox. Surprisingly, SQ3370 also induced regression of the non-injected tumor and enhanced T-cell infiltration in both injected and noninjected tumors. We hypothesize that activating Dox at a local site with SQ3370 promotes activation of the native immune system against the tumor. Thus, SQ3370 represents a new therapeutic modality to treat solid tumors by using a drug with known efficacy, Dox, and expanding its therapeutic window. SQ3370 could potentially also benefit patients with widely disseminated or micro-metastatic lesions.MethodsSQ3370-001 (NCT04106492), the first-in-human Phase 1 study, is currently open in the United States and Australia to treat patients with advanced solid tumors. SQ3370-001 is enrolling patients ≥ 18 years of age with an injectable local or metastatic lesion, for which published data indicates responsiveness to anthracyclines. Patients must be relapsed or refractory following standard of care therapy and must not have received more than 225 mg/m2 of Dox (or equivalent anthracycline). Each cycle will be for 21 days with no limit on total cycles. Primary objectives include determining the safety, tolerability, and recommended Phase 2 dose. Additional objectives include assessment of the pharmacokinetic profile, preliminary efficacy per RECIST 1.1, and immune response.ResultsN/AConclusionsN/AAcknowledgementsThe authors would like to thank the National Institutes of Health (NIH), the National Science Foundation (NSF), and Y Combinator.Ethics ApprovalThis study was approved by:1. The Institutional Review Board (IRB) of Stanford University; eProtocol Number: 54928.2. The IRB of The University of Texas MD Anderson Cancer Center; IRB ID Number: 2020-0185_MOD001.3. Western IRB, on behalf of The Angeles Clinic and Research Institute and Henry Ford Health System IRB Office; IRB Tracking Number: 20200758.4. Bellberry Limited Human Research Ethics Committee, on behalf of Royal North Shore Hospital and Chris O’Brien Lifehouse; Application Number: 2019-10-848.ReferencesMattarollo SR, Loi S, Duret H, Ma Y, Zitvogel L, Smyth MJ. Pivotal role of innate and adaptive immunity in anthracycline chemotherapy of established tumors. Cancer Res 2011;71:4809–4820.Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G. Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity 2013;39:74–88.

Neurological Assessment Using a Quantitative Sensory Test in Patients with Chronic Unilateral Orofacial Pain

Background: Quantitative Sensory Testing (QST) has been used in clinical and experimental settings to establish sensory assessment for different types of pains, and may be a useful tool for the assessment of orofacial pain, but this premise needs to be tested. Objective: The aim of the study was to evaluate responses to thermal stimuli between painful and non-painful facial sites in subjects with orofacial pain using QST. Methods: A total of 60 participants (5o females: 28-83 years; 10 males: 44-81 years) with unilateral orofacial pain were recruited from the Orofacial Pain Clinic at the Pain Management and Research Centre, Royal North Shore Hospital, Sydney, Australia. The study followed the methods of limits of the German Research Network testing four modalities of thermal thresholds, the Warm Sensation, the Cold Sensation, the Heat Pain and the Cold Pain using a TSA-II Neurosensory Analyser. The results were compared to the results from the unaffected side of the same patient on the same area and a single t test statistical analysis was performed, where a p value of less than 0.05 was considered significant. Results: The Mean Difference for Cold Sensation between the pain side and the non-pain side was 0.48 °C ± 1.5 (t= 2.466, p=0.017), 0.68 °C ± 2.04 for Warm Sensation (t= -2.573, p= 0.013), 2.56 °C ± 2.74 for Cold Pain (t= 7.238, p<0.001) and -1.21 °C ± 2.59 for Hot Pain (t= -3.639, p=0.001). Conclusion: The study showed that QST methods using thermal stimuli could be used to evaluate sensory dysfunction in orofacial pain patients using the specific parameters of cool and warm sensation, and cold and hot pain.