Introduction Patients considering total joint arthroplasty often search for information online regarding surgery, however little is known about the specific topics that patients search for and the nature of the information provided. Google compiles frequently asked questions associated with a search term using machine learning and natural language processing. Links to individual websites are provided to answer each question. Analysis of this data may help improve understanding of patient concerns and inform more effective counseling. Methods Search terms were entered into Google for total hip and total knee arthroplasty. Frequently asked questions and associated websites were extracted to a database using customized software. Questions were categorized by topic; websites were categorized by type. JAMA Benchmark Criteria were used to assess website quality. Pearson’s chi-square and Student’s t-tests were performed as appropriate. Results A total of 620 questions (305 TKA, 315 THA) were extracted with 602 associated websites. The most popular question topics were Specific Activities (23.5%), Indications/Management (15.6%), and Restrictions (13.4%). Questions related to Pain were more common in the TKA group (23.0% vs 2.5%, p<0.001) compared to THA. The most common website types were Academic (31.1%), Commercial (29.2%), and Social Media (17.1%). JAMA scores (0-4) were highest for Government websites (mean 3.92, p=0.005). Conclusion The most frequently asked questions on Google related to total joint arthroplasty are related to arthritis management, rehabilitation, and ability to perform specific tasks. A sizeable proportion of health information provided originate from non-academic, non-government sources (64.4%), with 17.1% from social media websites.

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In prior work we reported that advanced stage, drug-resistant pancreatic cancer cells (the SW1990 line) can be sensitized to the EGFR-targeting tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib by treatment with 1,3,4-O-Bu3ManNAc (Bioorg. Med. Chem. Lett. (2015) 25(6):1223-7). Here we provide mechanistic insights into how this compound inhibits EGFR activity and provides synergy with TKI drugs. First, we showed that the sialylation of the EGFR receptor was at most only modestly enhanced (by ∼20 to 30%) compared to overall ∼2-fold increase in cell surface levels of this sugar. Second, flux-driven sialylation did not alter EGFR dimerization as has been reported for cancer cell lines that experience increased sialylation due to spontaneous mutations. Instead, we present evidence that 1,3,4-O-Bu3ManNAc treatment weakens the galectin lattice, increases the internalization of EGFR, and shifts endosomal trafficking towards non-clathrin mediated (NCM) endocytosis. Finally, by evaluating downstream targets of EGFR signaling, we linked synergy between 1,3,4-O-Bu3ManNAc and existing TKI drugs to a shift from clathrin-coated endocytosis (which allows EGFR signaling to continue after internalization) towards NCM endocytosis, which targets internalized moieties for degradation and thereby rapidly diminishes signaling.

Study Design. Retrospective study of prospectively collected data. Objective. To determine the incidence, timing, risk factors, and clinical implications of postoperative hematoma requiring reoperation after anterior cervical discectomy and fusion (ACDF). Summary of Background Data. Postoperative hematomas requiring reoperation are rare but potentially catastrophic complications after ACDF. However, there has been a lack of large cohort studies investigating these complications in the ACDF population despite increasing outpatient procedure volume. Methods. Patients who underwent ACDF in the 2012 to 2016 National Surgical Quality Improvement Program database were identified. The primary outcome was an occurrence of hematoma requiring reoperation within 30 days postoperatively. Risk factors for this outcome were identified using multivariate regression. Postoperative length of stay, subsequent complications, and mortality were compared between patients who did and did not develop a hematoma requiring reoperation. Results. A total of 37,261 ACDF patients were identified, of which 148 (0.40%) developed a hematoma requiring reoperation (95% confidence interval [CI], 0.33%–0.46%). Of the cases that developed this complication, 37% occurred after discharge. Risk factors for the development of hematoma requiring reoperation were multilevel procedures (most notably ≥3 levels, relative risk [RR] = 3.14, 95% CI = 1.86–5.32, P < 0.001), preoperative international normalized ratio >1.2 (RR = 2.85, 95% CI = 1.42–5.71, P = 0.006), lower BMI (notably body mass index ≤24, RR = 2.11, 95% CI = 1.21–3.67, P = 0.008), American Society of Anesthesiologists classification ≥3 (RR = 2.07, 95% CI = 1.47–2.91, P < 0.001), preoperative anemia (RR = 1.71, 95% CI = 1.12–2.63, P = 0.027), and male sex (RR = 1.67, 95% CI = 1.18–2.37, P = 0.004). In addition, patients who developed a hematoma requiring reoperation before discharge had a longer length of stay. Further, those who developed a hematoma requiring reoperation were at higher risk for subsequent ventilator requirement, deep wound infection, pneumonia, and reintubation. Conclusion. Postoperative hematoma requiring reoperation occurred in approximately 1 in 250 patients after ACDF. High-risk patients should be closely monitored through the perioperative period. Level of Evidence: 3

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Metastatic human pancreatic cancer cells (the SW1990 line) that are resistant to the EGFR-targeting tyrosine kinase inhibitor drugs (TKI) erlotinib and gefitinib were treated with 1,3,4-O-Bu3ManNAc, a “metabolic glycoengineering” drug candidate that increased sialylation by ∼12-fold. Consistent with genetic methods previously used to increase EGFR sialylation, this small molecule reduced EGF binding, EGFR transphosporylation, and downstream STAT activation. Significantly, co-treatment with both the sugar pharmacophore and the existing TKI drugs resulted in strong synergy, in essence re-sensitizing the SW1990 cells to these drugs. Finally, l,3,4-O-Bu3ManNAz, which is the azido-modified counterpart to l,3,4-O-Bu3ManNAc, provided a similar benefit thereby establishing a broad-based foundation to extend a “metabolic glycoengineering” approach to clinical applications.