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Background: The COVID-19 pandemic significantly impacted procedural volumes across all surgical specialties. This study aims to assess trends two years after the start of the pandemic and analyze the current surgical volume in Otolaryngology-Head and Neck Surgery.Methods: The COVID-19 TriNetX database, consisting of 67 health care organizations (HCOs) was utilized to collect de-identified data patients that underwent otolaryngologic surgical procedures from February 1, 2018 to January 31, 2022. The pre-pandemic (2018 to 2019) and post-pandemic (2020 to 2021) periods were analyzed and compared for surgical volumes by season, surgical subspecialty, and procedure type. Student's t-test was utilized to test for statistical significance of trends between seasonal averages pre- and post-pandemic. Results: A total of 2,005,796 otolaryngology surgical procedures from 45 HCOs were included. When comparing the average monthly post-pandemic (2020 and 2021) volumes to their pre-pandemic (2018 and 2019) seasonal counterparts, there were statistically significant decreases in the averages of all seasons. Post-pandemic seasonal volumes assessed by individual years depicted a significant decline in the total otolaryngology surgical volumes in all seasons, with the steepest reduction from Winter 2019 to Spring 2020.Conclusions: Specialties that experienced significant reductions in volume without sufficient evidence of rebounding trends include paediatric otolaryngology and otology, while general/rhinology/endoscopy, laryngology, head and neck surgery, and facial plastics and reconstructive surgery are trending towards pre-pandemic baselines.

To determine the impact of sociodemographic factors on post-operative performance outcomes among PCI recipients across the world.A qualitative systematic review of PubMed, Scopus, Web of Science, and Embase was undertaken for studies analyzing the association of sociodemographic factors with measures of PCI outcomes published before July 18, 2021. Study quality assessment tools from the National Institutes of Health (NIH) were used to assess for risk of bias.Out of 887 unique abstracts initially retrieved, 45 papers were included in the final qualitative systematic review. Sociodemographic disparities in PCI outcomes from 4702 PCI recipients were studied in 19 countries, with 14 studies conducted in the United States of America, published within the years of 1999 to 2021. Parental education and socioeconomic status (e.g. income) were the most investigated disparities in PCI outcomes with 24 and 17 identified studies, respectively.Socioeconomic status was a consistently reported determinant of PCI outcomes in the USA and elsewhere, and parental education, the most reported disparity, consistently impacted outcomes in countries outside the USA. This study is limited by our inability to perform a meta-analysis given the lack of standardization across measures of sociodemographic variables and assessment measures for PCI outcomes. Future studies should address the literature gap on racial and ethnic disparities among PCI outcomes and use standardized measures for sociodemographic variables and PCI outcomes to facilitate meta-analyses on the topic. Targeting the mechanisms of these disparities may mitigate the impact of the sociodemographic factors on PCI outcomes.

Considerable evidence shows that the vestibular system contributes to adjusting sympathetic nervous system activity to maintain adequate blood pressure during movement and changes in posture. However, only a few prior experiments entailed recordings in conscious animals from brainstem neurons presumed to convey baroreceptor and vestibular inputs to neurons in the rostral ventrolateral medulla (RVLM) that provide inputs to sympathetic preganglionic neurons in the spinal cord. In this study, recordings were made in conscious felines from neurons in the medullary lateral tegmental field (LTF) and nucleus tractus solitarius (NTS) identified as regulating sympathetic nervous system activity by exhibiting changes in firing rate related to the cardiac cycle, or cardiac-related activity (CRA). Approximately 38% of LTF and NTS neurons responded to static 40° head up tilts with a change in firing rate of ~50%. However, few of these neurons responded to 10° sinusoidal rotations in the pitch plane, in contrast to prior findings in decerebrate animals that the firing rates of both NTS and LTF neurons are modulated by small-amplitude body rotations. Thus, as previously demonstrated for RVLM neurons, in conscious animals NTS and LTF neurons only respond to large rotations that lead to changes in sympathetic nervous system activity. The similar responses to head-up rotations of LTF and NTS neurons with those documented for RVLM neurons suggest that LTF and NTS neurons are components of the vestibulo-sympathetic reflex pathway. However, a difference between NTS/LTF neurons and RVLM was variability in CRA over time. This variability was significantly greater for RVLM neurons, raising the hypothesis that the responsiveness of these neurons to baroreceptor input is adjusted based on the animal’s vigilance and alertness.

Osteosarcoma (OS) is the most common primary bone cancer and disproportionately affects pediatric and adolescent patients. Survival rates for OS patients with metastatic disease is only 15-30% and has not improved in several decades. Novel treatments targeting specifically metastatic markers of OS are needed. ALDH1A1 is a known cancer stem marker and highly expressed in metastatic cancer cells. Disulfiram (Antabuse®) is an FDA-approved anti-alcoholism drug which acts as an ALDH inhibitor and has been widely studied for repurposing as an effective therapy in multiple types of cancer. Disulfiram cytotoxicity in cancer cells has been shown to be copper-dependent due to its ability to function as a bivalent metal ion chelator of copper (Cu). Cu concentrations of OS patient tumors, human OS cell lines, and OS patient plasma were determined using a Perkin Elmer AAnalyst 600 atomic absorption spectrophotometer. qPCR using custom primers for ALDH1A1 was performed on human OS cell lines and OS patient tumors differing in metastatic potential. OS cell cytotoxicity assays were performed with disulfiram and copper chloride after 24 hours of treatment. Balb/C mice were challenged intratibial with Luciferase+ K7M2, and treated with disulfiram and copper gluconate by oral gavage. Primary tumor growth and pulmonary metastases were monitored using the IVIS XR live imaging system. Metastatic OS patient tumors displayed significantly increased ALDH1A1 expression compared to non-metastatic OS patient tumors (n=8, P=0.02). Metastatic OS tumors displayed decreased Cu levels compared to non-metastatic OS tumors (n=18, P=0.05). Conversely, serum Cu levels from OS patients with metastases demonstrated increased blood Cu levels compared with non-metastatic patients (n=24, P=0.01). qPCR displayed ALDH1A1 expression was significantly increased in highly metastatic human OS cell lines LM2 and LM7 compared to low metastatic SaOS-2 (n=3, P=0.002). Intracellular Cu was inversely proportional to metastatic phenotype in human OS cell lines SaOS-2>LM2>LM7. Copper chloride displayed clear potentiation of disulfiram resulting in a strong cytotoxic effect in both SaOS-2 and LM7. Doxorubicin IC50 for SaOS-2 and LM7 was 1.2 µM and 2.5 µM respectively, while disulfiram IC50 with a 50 nM copper chloride supplement for SaOS-2 and LM7 was 1.2 µM and 0.6 µM respectively. In our preclinical mouse model, after primary tumor resection, differences in recurrent growth at amputation site were seen between treatment groups. Disulfiram and copper gluconate combination treated mice displayed 13% (1/8) recurrence rates at the primary tumor amputation site, while untreated animals displayed 60% (9/15) recurrence rates. This study demonstrates that both ALDH1A1 and Cu bioavailability are altered between low and highly metastatic OS. Since ALDH1A1 is a direct target and Cu is a potentiator of disulfiram, this supports the potential of using this repurposed drug in combination with surgical and chemotherapy interventions for metastatic OS. Citation Format: Jonathan B. Mandell, Nerone Douglas, Vrutika Ukani, Carolyn Anderson, Jan Beumer, Rebecca Watters, Kurt Weiss. Altered ALDH1A1 expression and cellular copper levels between low and highly metastatic osteosarcoma provides a case for novel repurposing of disulfiram [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 345.