A Novel Instrument Holder to Improve Operative Efficiency in Endoscopic Laryngeal and Airway Surgery.

OBJECTIVE: Receiving instruments from surgical technicians during endoscopic laryngeal and airway microsurgery (ELAM) has challenges including repeated, expeditious handling of delicate instruments and passing them to the surgeon's hand opposite of where the surgical assistant is standing. Optimizing this interaction may reduce surgical errors and improve operative efficiency. METHODS: A proprietary ELAM instrument holder was attached to both sides of the operating room bed. The device consisted of an articulating arm with custom silicone inserts mounted on a tray (storing up to three endoscopic instruments). ELAM cases were randomized to be performed either with (device) or without the holder (control). Using custom software, instrument pass time (IPT), instrument drop rate (IDR), and communication errors (eg handing incorrect instruments) were manually recorded. Qualitative use metrics relating to overall device satisfaction were also obtained. RESULTS: Data were collected from 25 device and 23 control cases among three different laryngologists. Average IPT was nearly three times quicker for the device (0.80 s, n = 1175 passes) compared with controls (2.09 s, n = 1208 passes) [p < 0.001]. IPT interquartile range was five times higher for control (1.65 s) versus device cases (0.42 s). IDR was not significantly different [p = 0.48]; however, device cases had significantly lower communication errors compared to control cases [p = 0.01]. Surgeons and surgical assistants were similarly satisfied with the device on a 5-point Likert scale (mean: 4.2/5, standard deviation: 0.92). CONCLUSION: The proposed endoscopic instrument holder can improve ELAM operative workflow by reducing instrument passing time and variability without increasing IDR. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3492-3498, 2023.

Correction: Nail in the Coffin or Lifeline? Evaluating the Electoral Impact of COVID-19 on President Trump in the 2020 Election.

[This corrects the article DOI: 10.1007/s11109-022-09826-x.].

Nail in the Coffin or Lifeline? Evaluating the Electoral Impact of COVID-19 on President Trump in the 2020 Election.

From the onset of the first confirmed case of COVID-19 in January 2020 to Election Day in November, the United States experienced over 9,400,000 cases and 232,000 deaths. This crisis largely defined the campaign between former Vice President Joe Biden and President Donald Trump, centering on the Trump administration's efforts in mitigating the number of cases and deaths. While conventional wisdom suggested that Trump and his party would lose support due to the severity of COVID-19 across the country, such an effect is hotly debated empirically and theoretically. In this research, we evaluate the extent to which the severity of the COVID-19 pandemic influenced support for President Trump in the 2020 election. Across differing modeling strategies and a variety of data sources, we find evidence that President Trump gained support in counties with higher COVID-19 deaths. We provide an explanation for this finding by showing that voters concerned about the economic impacts of pandemic-related restrictions on activity were more likely to support Trump and that local COVID-19 severity was predictive of these economic concerns. While COVID-19 likely contributed to Trump's loss in 2020, our analysis demonstrates that he gained support among voters in localities worst affected by the pandemic. Supplementary Information: The online version contains supplementary material available at 10.1007/s11109-022-09826-x.

Scaffold stiffness influences breast cancer cell invasion via EGFR-linked Mena upregulation and matrix remodeling.

Clinically, increased breast tumor stiffness is associated with metastasis and poorer outcomes. Yet, in vitro studies of tumor cells in 3D scaffolds have found decreased invasion in stiffer environments. To resolve this apparent contradiction, MDA-MB-231 breast tumor spheroids were embedded in 'low' (2 kPa) and 'high' (12 kPa) stiffness 3D hydrogels comprised of methacrylated gelatin/collagen I, a material that allows for physiologically-relevant changes in stiffness while matrix density is held constant. Cells in high stiffness materials exhibited delayed invasion, but more abundant actin-enriched protrusions, compared to those in low stiffness. We find that cells in high stiffness had increased expression of Mena, an invadopodia protein associated with metastasis in breast cancer, as a result of EGFR and PLCγ1 activation. As invadopodia promote invasion through matrix remodeling, we examined matrix organization and determined that spheroids in high stiffness displayed a large fibronectin halo. Interestingly, this halo did not result from increased fibronectin production, but rather from Mena/α5 integrin dependent organization. In high stiffness environments, FN1 knockout inhibited invasion while addition of exogenous cellular fibronectin lessened the invasion delay. Analysis of fibronectin isoforms demonstrated that EDA-fibronectin promoted invasion and that clinical invasive breast cancer specimens displayed elevated EDA-fibronectin. Combined, our data support a mechanism by which breast cancer cells respond to stiffness and render the environment conducive to invasion. More broadly, these findings provide important insight on the roles of matrix stiffness, composition, and organization in promoting tumor invasion.

Alternatively activated macrophage-derived secretome stimulates ovarian cancer spheroid spreading through a JAK2/STAT3 pathway.

High-grade serous ovarian cancer (HGSOC) metastasizes when tumor spheroids detach from the primary tumor and re-attach throughout the peritoneal cavity. Once the cancer cells have implanted in these new sites, the development of metastatic lesions is dependent on the disaggregation of cancer cells from the spheroids and subsequent expansion across the collagenous extracellular matrix (ECM). As HGSOC progresses an increase in alternatively activated macrophages (AAMs) in the surrounding ascites fluid has been observed and AAMs have been shown to enhance tumor invasion and growth in a wide range of cancers. We hypothesized that soluble factors from AAMs in the peritoneal microenvironment promote the disaggregation of ovarian cancer spheroids across the underlying ECM. We determined that co-culture with AAMs significantly increased HGSOC spheroid spreading across a collagen matrix. Multivariate modeling identified AAM-derived factors that correlated with enhanced spread of HGSOC spheroids and experimental validation showed that each individual cell line responded to a distinct AAM-derived factor (FLT3L, leptin, or HB-EGF). Despite this ligand-level heterogeneity, we determined that the AAM-derived factors utilized a common signaling pathway to induce spheroid spreading: JAK2/STAT3 activation followed by MMP-9 mediated spreading. Furthermore, immunostaining demonstrated that FLT3, LEPR, EGFR, and pSTAT3 were upregulated in metastases in HGSOC patients, with substantial patient-to-patient heterogeneity. These results suggest that inhibiting individual soluble factors will not inhibit AAM-induced effects across a broad group of patients; instead, the downstream JAK2/STAT3/MMP-9 pathway should be examined as potential therapeutic targets to slow metastasis in ovarian cancer.