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Objectives: Early on during the COVID-19 pandemic, the US Centers for Medicare & Medicaid Services (CMS) and other government as well as medical institutions recommended that surgeons postpone nonessential surgeries. The aim of our study is to examine the impact of the COVID-19 pandemic on otolaryngology surgical training by evaluating changes in surgical volumes through various time points relative to the height of the pandemic. Methods: We performed a retrospective review of all surgical cases performed by the Otolaryngology-Head and Neck Surgery department at a tertiary care academic center from 3 time periods: July 1st, 2018, to June 30th, 2019; July 1st, 2019, to June 30th, 2020; and July 1st, 2020, to June 30th, 2021. Results: From the 2018-19 period to the 2020-21 period, the total number of overall cases decreased by 9.9%, from 2386 to 2148 cases. During this same time duration, the number of key indicator cases decreased by 13.4%, from 1715 to 1486 cases. Relative to other cases, ethmoidectomy, rhinoplasty, and stapes/OCR cases decreased the most during the 2019-20 period by 41.9%, 41.8%, and 29.5%, respectively. From the 2018-19 period to the 2020-21 period, thyroid/parathyroid cases decreased the most by 35.4%. Only ethmoidectomy and oral cavity cases showed increases during this period at 9.7% and 24.4%, respectively. Conclusions: Although case volumes have stayed relatively constant, key indicator case volumes at the present tertiary care academic center have not yet fully recovered from the COVID-19 pandemic. Efforts must be made to determine how this has impacted residency surgical education.

Understanding dexamethasone's effect on the immune microenvironment in glioma patients is of key importance. We performed a comprehensive literature review using the NCBI PubMed database for all articles meeting the following search criteria. ((dexamethasone[All Fields]) AND (glioma or glioblastoma)[Title/Abstract]) AND (immune or T cell or B cell or monocyte or neutrophil or macrophage). Forty-three manuscripts were deemed relevant to the topic at hand. Multiple clinical studies have linked dexamethasone use to decreased overall survival while preclinical studies in murine glioma models have demonstrated decreased tumor-infiltrating lymphocytes after dexamethasone administration.

INTRODUCTION As the incidence of elderly spinal cord injury rises, improved understanding of risk profiles and outcomes is needed. This review summarizes clinical characteristics, management, and outcomes specific to the elderly (≥65-years) with acute traumatic central cord syndrome in the USA. EVIDENCE AQUISITION Literature review of the PubMed, Embase, and CINAHL databases (01/2007-03/2020) regarding elderly subjects with acute traumatic central cord syndrome. EVIDENCE SYNTHESIS Nine studies met inclusion criteria. Acute traumatic central cord syndrome was more common among married (50%), Caucasian (22-71%) males (63-86%) with an annual income

Background Macrophages are the most common infiltrating immune cells in gliomas and play a wide variety of pro-tumor and anti-tumor roles. However, the different subpopulations of macrophages and their effects on the tumor microenvironment remain poorly understood. Methods We combined new and previously published single-cell RNA-seq data from 98,015 single cells from a total of 66 gliomas to profile 19,331 individual macrophages. Results Unsupervised clustering revealed a pro-tumor subpopulation of bone marrow-derived macrophages characterized by the scavenger receptor MARCO, which is almost exclusively found in IDH1-wild-type glioblastomas. Previous studies have implicated MARCO as an unfavorable marker in melanoma and non-small cell lung cancer; here, we find that bulk MARCO expression is associated with worse prognosis and mesenchymal subtype. Furthermore, MARCO expression is significantly altered over the course of treatment with anti-PD1 checkpoint inhibitors in a response-dependent manner, which we validate with immunofluorescence imaging. Conclusions These findings illustrate a novel macrophage subpopulation that drives tumor progression in glioblastomas and suggest potential therapeutic targets to prevent their recruitment.

International audience; In two cohorts of patients with glioblastoma who received anti-PD-1, Sonabend and colleagues show that ERK1/2 phosphorylation, detected by immunohistochemistry, provides a biomarker for MAPK/ERK pathway activity and better survival on this therapy. Only a subset of recurrent glioblastoma (rGBM) responds to anti-PD-1 immunotherapy. Previously, we reported enrichment of BRAF/PTPN11 mutations in 30% of rGBM that responded to PD-1 blockade. Given that BRAF and PTPN11 promote MAPK/ERK signaling, we investigated whether activation of this pathway is associated with response to PD-1 inhibitors in rGBM, including patients that do not harbor BRAF/PTPN11 mutations. Here we show that immunohistochemistry for ERK1/2 phosphorylation (p-ERK), a marker of MAPK/ERK pathway activation, is predictive of overall survival following adjuvant PD-1 blockade in two independent rGBM patient cohorts. Single-cell RNA-sequencing and multiplex immunofluorescence analyses revealed that p-ERK was mainly localized in tumor cells and that high-p-ERK GBMs contained tumor-infiltrating myeloid cells and microglia with elevated expression of MHC class II and associated genes. These findings indicate that ERK1/2 activation in rGBM is predictive of response to PD-1 blockade and is associated with a distinct myeloid cell phenotype.

Introduction Return to work (RTW) is an important milestone of mild traumatic brain injury (mTBI) recovery. The objective of this study was to evaluate whether baseline clinical variables, three-month RTW, and three-month postconcussional symptoms (PCS) were associated with six-month RTW after mTBI. Methods Adult subjects from the prospective multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot study with mTBI (Glasgow Coma Scale 13–15) who were employed at baseline, with completed three- and six-month RTW status, and three-month Acute Concussion Evaluation (ACE), were extracted. Univariate and multivariable analyses were performed for six-month RTW, with focus on baseline employment, three-month RTW, and three-month ACE domains (physical, cognitive, sleep, and/or emotional postconcussional symptoms (PCS)). Odds ratios (OR) and 95% confidence intervals [CI] were reported. Significance was assessed at p Results In 152 patients aged 40.7 ± 15.0 years, 72% were employed full-time at baseline. Three- and six-month RTW were 77.6% and 78.9%, respectively. At three months, 59.2%, 47.4%, 46.1% and 31.6% scored positive for ACE physical, cognitive, sleep, and emotional PCS domains, respectively. Three-month RTW predicted six-month RTW (OR = 19.80, 95% CI [7.61–51.52]). On univariate analysis, scoring positive in any three-month ACE domain predicted inability for six-month RTW (OR = 0.10–0.11). On multivariable analysis, emotional symptoms predicted inability to six-month RTW (OR = 0.19 [0.04–0.85]). Subjects who scored positive in all four ACE domains were more likely to be unable to RTW at six months (4 domains: 58.3%, vs. 0-to-3 domains: 9.5%; multivariable OR = 0.09 [0.02–0.33]). Conclusions Three-month post-injury is an important time point at which RTW status and PCS should be assessed, as both are prognostic markers for six-month RTW. Clinicians should be particularly vigilant of patients who present with emotional symptoms, and patients with symptoms across multiple PCS categories, as these patients are at further risk of inability to RTW and may benefit from targeted evaluation and support.

Diversity is a key feature in the glioma ecosystem. Adaptation to a changing tumor microenvironment is achieved through cellular and metabolic plasticity. Here we show that slow-cycling, astrocyte-like glioma cell subpopulations activate distinct metabolic programs, rendering them susceptible to novel treatments. We performed multi-omics analysis on transgenic murine glioma models to characterize cellular heterogeneity. Bulk RNAseq on targeted time-dependent biopsies combined with scRNAseq uncovered distinct tumor cell populations, including a quiescent, astrocyte-like population relatively insensitive to conventional chemotherapy targeting proliferating cells. Using scRNAseq, we identified a persistently conserved astrocytic population in human IDH1-mt/wt high-grade gliomas. This astrocytic tumor population was more abundant in mouse models with constitutive Notch activation, however it was associated with alterations in several other transcriptional programs, suggesting that targeted therapies would likely be ineffective at eradicating it. Gene ontology analysis revealed enrichment in mitochondrial genes specifically regulating oxidative phosphorylation and tricarboxylic acid cycle. Energetic, lipidomic and metabolomic analyses revealed significant mitochondrial β-fatty acid oxidation and lipid catabolism, with less effective oxygen consumption rate and higher basal oxidative stress. Furthermore, this astrocytic tumor population had depleted levels of basal GSH and was more sensitive to reactive oxygen species. Leveraging this metabolic vulnerability, we performed drug screens and found that therapeutic inhibition of complex I or GPX4 was highly effective and synergistic. GPX4 inhibition induced ferroptosis, a newly-discovered form of programmed non-necroptotic cell death mediated by iron-driven lipid peroxidation. Using scRNAseq and RNAscope on ex vivo slice cultures from murine and human gliomas, we found that GPX4 inhibition and ferroptosis induction in the glioma microenvironment selectively eradicated the quiescent astrocytic subpopulation whereas proliferating glioma were less sensitive. Our data therefore supports a novel treatment paradigm, employing metabolic strategies, such as ferroptosis, in conjunction with chemotherapy and RT to target distinct tumor cell populations with different therapeutic vulnerabilities.

Unlike other malignancies, ovarian cancer (OC) creates a complex tumor microenvironment with distinctive peritoneal ascites consisting of a mixture of several immunosuppressive cells which impair the ability of the patient's immune system to fight the disease. The poor survival rates observed in advanced stage OC patients and the lack of effective conventional therapeutic options have been attributed in large part to the immature dendritic cells (DCs), IL-10 secreting regulatory T cells, tumor-associated macrophages, myeloid-derived suppressor cells, and cancer stem cells that secrete inhibitory cytokines. This review highlights the critical role played by the intraperitoneal presence of IL-10 in the generation of an immunosuppressive tumor microenvironment. Further, the effect of antibody neutralization of IL-10 on the efficacy of DC and chimeric antigen receptor T-cell vaccines will be discussed. Moreover, we will review the influence of IL-10 in the promotion of cancer stemness in concert with the NF-κB signaling pathway with regard to OC progression. Finally, understanding the role of IL-10 and its crosstalk with various cells in the ascitic fluid may contribute to the development of novel immunotherapeutic approaches with the potential to kill drug-resistant OC cells while minimizing toxic side effects.

The novel coronavirus commonly referred to as COVID-19 became a global pandemic in the March of 2020 and createdunprecedented challenges for health care systems worldwide. Early case reports demonstrated a high risk of aerosolizationand infection of operating room staff during endoscopic endonasal approaches, highlighting the need for safe managementstrategies in patients with COVID-19 with acute pathology. During periods of epidemiologic infectious surges, elective caseshave often been suspended. However, patients presenting with urgent pathology, such as pituitary apoplexy or acute visualcompromise from sellar or parasellar lesions still require treatment regardless of infectious status. Here, we present a caseof an asymptomatic COVID-19 patient with progressive vision loss that underwent successful microscopic resection ofpituitary adenoma, without evidence of spread to the operating room staff. We hypothesize that during microscopicapproaches to the sella, there is relatively less forceful irrigation, and as a result, potentially less aerosolization. This maydecrease the risk of viral spread to the surgeons and the operating room staff. Additionally, we report that fluorescent insitu hybridization studies of tumor tissue for SARS-CoV-2 may not reliably be able to detect viral infections. In conclusion,for asymptomatic patients at high risk for COVID, microscopic transsphenoidal approaches may provide a safer alternative.These patients should undergo preoperative testing, and repeat testing should be considered if possible for negative results.Proper PPE should however still be utilized to maximize safety of the operating room staff.

Biomedical data are usually analyzed at the univariate level, focused on a single primary outcome measure to provide insight into systems biology, complex disease states, and precision medicine opportunities. More broadly, these complex biological and disease states can be detected as common factors emerging from the relationships among measured variables using multivariate approaches. ‘Syndromics’ refers to an analytical framework for measuring disease states using principal component analysis and related multivariate statistics as primary tools for extracting underlying disease patterns. A key part of the syndromic workflow is the interpretation, the visualization, and the study of robustness of the main components that characterize the disease space. We present a new software package,syndRomics, an open-source R package with utility for component visualization, interpretation, and stability for syndromic analysis. We document the implementation ofsyndRomicsand illustrate the use of the package in case studies of neurological trauma data.

Additional file 3: Supplementary figures.

Background Preclinical studies require models that recapitulate the cellular diversity of human tumors and provide insight into the drug sensitivities of specific cellular populations. The ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity. Methods We combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses in individual patients. We applied this approach to drug perturbations on slices derived from six glioblastoma (GBM) resections to identify conserved drug responses and to one additional GBM resection to identify patient-specific responses. Results We used scRNA-seq to demonstrate that acute slice cultures recapitulate the cellular and molecular features of the originating tumor tissue and the feasibility of drug screening from an individual tumor. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients. Etoposide has a conserved impact on proliferating tumor cells, while panobinostat treatment affects both tumor and non-tumor populations, including unexpected effects on the immune microenvironment. Conclusions Acute slice cultures recapitulate the major cellular and molecular features of GBM at the single-cell level. In combination with scRNA-seq, this approach enables cell type-specific analysis of sensitivity to multiple drugs in individual tumors. We anticipate that this approach will facilitate pre-clinical studies that identify effective therapies for solid tumors.

Trans-oral vocal fold injection is the only non-percutaneous approach for vocal fold augmentation routinely performed in awake patients. With this approach, the operator manipulates a curved needle from the oral cavity to the glottis, visualizing with assistant-driven flexible trans-nasal or surgeon-driven rigid peroral laryngoscopy. This is a technically challenging approach predicated on the coordinated abilities of the surgeon and assistant. Moreover, success is highly dependent on patient factors, as unfavorable anatomy or a strong oropharyngeal gag may preclude completion of the procedure. Despite this, the trans-oral approach provides excellent needle control allowing for high precision in directing needle placement and controlling the nature of vocal fold augmentation.

Postoperative stroke is a rare complication following carotid endarterectomy (CEA), but a major outcome endpoint in trials and in clinical practice. Many strokes with symptom onset in the immediate postoperative period are due to surgical-site thrombus. For this reason, management has historically consisted of emergent reoperation without angiography. There are, however, multiple possible etiologies for postoperative stroke including intracranial thromboembolism, tandem extracranial-intracranial occlusion, cerebral hemorrhage, and carotid dissection. Moreover, there have been important advances in the endovascular treatment of acute thrombo-embolic stroke using mechanical thrombectomy. Given the various etiologies for postoperative CEA stroke, optimal management remains controversial. Advances in endovascular and imaging techniques have challenged the historical dogma of emergent open carotid reoperation. In this chapter, we will outline the evidence related to postoperative CEA stroke, the various time courses, and etiologies of said postoperative strokes, along with evidence-based rationale to inform clinical decision-making.

Genotyping by sequencing (GBS) was used to analyze relationships among cowpea and asparagus bean landraces from southern Italy and to assess the utility of this technology to study taxonomy in a wider panel, including V. unguiculata cultigroups, subspecies, and other Vigna species. The analysis of SNPs derived from GBS highlighted that, among the cowpea landraces, the African samples were separated from the other material, while, for the Italian landraces, a certain clustering depending on seed color/pattern was observed in the dendrogram. When examining the V. unguiculata species complex, a clear separation between the two groups of wild subspecies, i.e., the allogamous wild perennials and the perennial out/inbreds, could be observed, the former representing the more ancestral wild progenitors of V. unguiculata. The species V. vexillata appeared more closely related to V. unguiculata than to the other Vigna species analyzed.

The development of a refrigerator with some modifications is the need of the era. In this work, development of a refrigerator employing the Peltier effect having volume of cooling as 3.6 cubic meters with dimensions 1.45m x 1m x 2.48m. is reported. The On/off controls are used in order to meet the sufficient refrigeration effect at the required tolerance of temperature. The performance of the device is tested by studying the cooling of a litre of water. The temperature was analysed from room temperature to a certain degree on minus side. The controls were reported to be efficient and given noteworthy performance.

Unlike other malignancies, ovarian cancer (OC) creates a complex tumor microenvironment with distinctive peritoneal ascites consisting of a mixture of several immunosuppressive cells which impair the ability of the patient's immune system to fight the disease. The poor survival rates observed in advanced stage OC patients and the lack of effective conventional therapeutic options have been attributed in large part to the immature dendritic cells (DCs), IL-10 secreting regulatory T cells, tumor-associated macrophages, myeloid-derived suppressor cells, and cancer stem cells that secrete inhibitory cytokines. This review highlights the critical role played by the intraperitoneal presence of IL-10 in the generation of an immunosuppressive tumor microenvironment. Further, the effect of antibody neutralization of IL-10 on the efficacy of DC and chimeric antigen receptor T-cell vaccines will be discussed. Moreover, we will review the influence of IL-10 in the promotion of cancer stemness in concert with the NF-κB signaling pathway with regard to OC progression. Finally, understanding the role of IL-10 and its crosstalk with various cells in the ascitic fluid may contribute to the development of novel immunotherapeutic approaches with the potential to kill drug-resistant OC cells while minimizing toxic side effects.

546 Background: RNA-based genomic assessment of recurrence risk is used to estimate chemotherapy benefit in patients with hormone-receptor positive (HR+)/Human Epidermal Growth Factor 2-negative ( ERBB2-) breast cancer (BC). While originally validated in patients who met established clinicopathologic guidelines for consideration of adjuvant chemotherapy, it is virtually used in all patients with early HR+/ ERBB2- BC regardless of clinical recurrence risk. Methods: We conducted a retrospective chart review of adult patients with early-stage (T1-3; N0; M0) HR+/ ERBB2- BC who underwent genomic risk assessment of recurrence using the Oncotype DX (Exact Sciences) 21-genes assay, between January 2015 and December 2020. Clinicopathologic features were collected to assess the clinical recurrence risk. A low clinical risk score (CRS) was defined as a tumor size ≤ 3 cm in diameter with histologic grade 1, or ≤ 2 cm with grade 2 or ≤ 1 cm with grade 3. A composite risk score of distant recurrent (RRS), derived from a COX model using data from the SOFT and TEXT trials ( https://rconnect.dfci.harvard.edu/CompositeRiskSTEPP/ ), was also computed for 374 patients for whom clinical data was available. RRS > 1.42 was defined as high. High genomic risk of recurrence was defined as a score (GRS) ≥25. The data was collected under IRB approval. Results: A total of 517 patients with early-stage disease were referred for genomic testing, and clinical data was available for 501 of them. Median age was 69 years (IQR=13), median tumor size 1.03 cm (IQR=0.9), and grade 2 histology (57.49%) was the most common. Results of recurrence risk, using the 3 prognostication methods, are summarized in Table. Within patients with low CRS (n=349), 9.17% had a high GRS, compared to 8.93% in patients with low RRS (n=280). In patients with grade 1 histology (n=130), 3.85% had a high GRS and 68.46% had tumors > 1cm, of whom only 4.49% had a high GRS. Tumor size > 1cm did not associate with a high GRS (Fisher’s Exact test; P=1.00). Conclusions: In patients with early HR+/ ERBB2- BC

12107 Background: Chemotherapy-induced nausea and vomiting (CINV), a major adverse effect of cancer treatment, can attenuate life quality. Multiple international antiemetic guidelines have recommended a 4-drug regimen (corticosteroid, 5-HT3 receptor antagonist, NK-1 receptor antagonist, and the antipsychotic medication olanzapine) for decreasing highly emetogenic CINV. This raised a question regarding whether antiemetic therapy regimens for highly emetogenic chemotherapy could be de-intensified, decreasing cost and side effects from anti-emetogenic agents. Methods: Study A221602 was developed to compare two olanzapine-containing antiemetic regimens, one with the use of an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Patients (pts) received intravenous highly emetogenic chemotherapy as either 1) cisplatin, given on one day, at a dose of ≥ 70 mg/m2, with or without other chemotherapy agent(s) or 2) doxorubicin (60 mg/m2) plus cyclophosphamide (600 mg/m2) on one day. Pts in both arms received 1) a 5-HT3 receptor antagonist (palonosetron 0.25 mg IV or ondansetron 8-16 mg IV or 16-24 mg PO,) on day one, 2) dexamethasone (12 mg PO, day one followed by 8 mg PO, days 2-4), and 3) olanzapine (10 mg/day PO, days 1 to 4). On Day 1, all agents were given prior to chemotherapy, with the exception that olanzapine could be taken prior to chemotherapy or at bedtime. Additionally, pts were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV; 346 pts) or a matching placebo (344 pts). The primary objective was to compare the proportion of patients with no nausea for 5 days following receipt of their chemotherapy between the two study arms. Results: While there was no suggestion of outcome differences on day 1 between the two study arms, fewer pts (7.4%; upper limit of the 95% confidence interval was 13.5%) without NK-1 receptor antagonists were without nausea for the complete 5-day study period. Conclusions: Per the study design, created to exclude a 10% benefit for NK-1 receptor antagonists, the results did not provide sufficient evidence to reject the hypothesis that the 4-drug regimen was superior to the protocol 3-drug regimen (p=0.24). Support: UG1CA189823; Clinical trial information: NCT03578081.