Background We have been investigating the molecular mechanisms of cisplatin-induced chemoresistance in head and neck squamous cell carcinoma (HNSCC). Based on our previous findings, the present study investigates how the Mre11, Rad50, and NBS1 (MRN) DNA repair complex interacts at the molecular level with the programmed cell death ligand 1 (PD-L1) in cisplatin-induced chemoresistance. Methods Human HNSCC cell lines were used to determine the role played by PD-L1 in cisplatin resistance. Initial experiments investigated PD-L1 expression levels in cells exposed to cisplatin and whether PD-L1 interacts directly with the MRN complex. Finally, in vitro studies and in vivo experiments on BALB/c nu/nu mice were performed to determine whether interference of PD-L1 or NBS1 synthesis modulated cisplatin resistance. Results Exposure to cisplatin resulted in PD-L1 being upregulated in the chemoresistant but not the chemosensitive cell line. Subsequent co-immunoprecipitation studies demonstrated that PD-L1 associates with NBS1. In addition, we found that the knockdown of either PD-L1 or NBS1 re-sensitised the chemoresistant cell line to cisplatin. Finally, but perhaps most importantly, synergy was observed when both PD-L1 and NBS1 were knocked down making the formerly chemoresistant strain highly cisplatin sensitive. Conclusions PD-L1 plays a pivotal role in cisplatin resistance in chemoresistant human HNSCC cell lines.

Background Treatment of aspirin-exacerbated respiratory disease AERD includes endoscopic sinus surgery ESS and aspirin desensitization AD with aspirin therapy a er desensitization ATAD The objective of this study was to determine the rate of major complications associated with aspirin use that resulted in the discontinuation of aspirin therapy Methods This study was a retrospective chart review of patients with AERD who underwent ESS AD and ATAD at a single AERD tertiary center between July and February Complications associated with aspirin that resulted in the discontinuation of aspirin therapy were analyzed via analysis of variance and logistic regression Results In total AERD patients underwent ESS with subsequent AD Ten patients discontinued therapy a er AD before starting ATAD Eight patients discontinued therapy a er starting ATAD There were patients with no complications throughout ATAD Reasons for discontinuation included gastritis upper gastrointestinal GI bleed anaphylaxis persistent sinonasal symptoms recurrent epistaxis asthma exacerbation and a nummular rash There was no significant correlation between complication rate and aspirin doses analysis of variance ANOVA F p = gender odds ratio OR confidence interval CI to p = age OR CI to p = or race/ethnicity OR CI to p = Conclusion AD with ATAD was associated with only a incidence of a clinically significant GI bleed and only a incidence of anaphylaxis A remaining patients discontinued aspirin therapy due to minor clinical sequelae These findings demonstrate that the majority of AERD patients tolerate AD with ATAD without any major complications © 2020 ARS-AAOA, LLC.

Background Aspirin‐exacerbated respiratory disease (AERD) is an aggressive respiratory tract inflammatory disorder manifesting as asthma, chronic rhinosinusitis with nasal polyposis, and a respiratory sensitivity to aspirin and nonsteroidal anti‐inflammatory drugs (NSAIDs). Corticosteroids, both systemic and topical/inhaled, are used to treat inflammation of the upper and lower airways. Our objective was to examine the potential impact of complete endoscopic sinus surgery (ESS) and aspirin desensitization (AD) on short‐term and long‐term corticosteroid use. Methods For this pilot study, a retrospective chart review of all patients with AERD who underwent ESS followed by AD was performed. Daily prednisone use, average daily prednisone dose, and inhaled corticosteroid use were analyzed at the following time points: preoperative, postoperative/pre‐AD, and 2 to 3 months, 4 to 6 months, 7 to 12 months, and 13 to 24 months following AD. Results A total of 125 patients underwent ESS followed by AD. Compared to preoperatively, patients who underwent ESS and AD were less likely to be on daily prednisone at all time points and upon long‐term follow‐up (32% preoperatively vs 10% at 13 to 24 months, McNemar's test = 9.00, p = 0.009). Average daily prednisone dose decreased from 10.6 ± 7.9 mg preoperatively to 3.8 ± 2.6 mg at 13 to 24 months following AD (Mann‐Whitney U; W = 122, p = 0.01). Similarly, high‐dose and medium‐dose inhaled corticosteroid use decreased from 18% to 7% and from 36% to 22% respectively (Pearson's chi‐square = 8.06, p = 0.05). Conclusion In our AERD cohort who underwent ESS followed by AD, there was an observed decrease in overall systemic and topical/inhaled corticosteroid use. These findings can have implications for treatment given the potentially hazardous side effects of corticosteroid use.

Recipients of donation after circulatory death (DCD) LTs historically have an increased risk of graft failure. Antibody induction (AI) with antithymocyte globulin (ATG) or anti‐interleukin 2 receptor (anti‐IL2R) immunotherapy may decrease the incidence of graft failure by mitigating ischemia/reperfusion injury. A retrospective review of the United Network for Organ Sharing (UNOS) database for LTs between 2002 and 2015 was conducted to determine whether ATG or anti‐IL2R AI was associated with graft survival in DCD. A secondary endpoint was postoperative renal function as measured by estimated glomerular filtration rate at 6 and 12 months. Among DCD recipients, ATG (hazard ratio [HR] = 0.71; P = 0.03), but not anti‐IL2R (HR = 0.82; P = 0.10), was associated with a decrease in graft failure at 3 years when compared with recipients without AI. ATG (HR = 0.90; P = 0.02) and anti‐IL2R (HR = 0.94; P = 0.03) were associated with a decreased risk of graft failure in donation after brain death (DBD) liver recipients at 3 years compared with no AI. When induction regimens were compared between DCD and DBD, only ATG (HR = 1.19; P = 0.19), and not anti‐IL2R (HR = 1.49; P < 0.01) or no AI (HR = 1.77; P < 0.01), was associated with similar survival between DCD and DBD. In conclusion, AI therapy with ATG was associated with improved longterm liver allograft survival in DCD compared with no AI. ATG was associated with equivalent graft survival between DCD and DBD, suggesting a beneficial role of immune cell depletion in DCD outcomes.

Background: Aspirin therapy and/or type 2 (T2) biologics are used in the management of aspirin-exacerbated respiratory disease (AERD). Objective: To identify the number of patients with AERD who tolerated aspirin therapy, yet due to persistent symptoms, incorporated T2 biologic management. Methods: A retrospective review was performed between July 2016 and June 2019. Patients with AERD and who underwent endoscopic sinus surgery (ESS), aspirin desensitization (AD), and at least 6 months of aspirin therapy (ATAD) after AD, and who remained biologic-naive up through this timepoint were included in the study. Introduction of a T2 biologic while on ATAD was the primary outcome. The secondary outcome was a change in a validated patient-reported outcome measure for chronic rhinosinusitis score between the postoperative predesensitization timepoint, and the 6-month postdesensitization timepoint, presented as means and compared by using the Student's t-test. Results: A total of 103 patients met inclusion criteria. Two patients (1.9%) ultimately supplemented ATAD with a T2 biologic. The mean outcomes measure test score after 6 months of ATAD for patients who received biologics was 40.5 versus 15 in those who did not receive biologics (p = 0.02). The mean differences between the postoperative predesensitization test score and the 6-month postdesensitization test score for patients who went on to receive biologics was an increase of 13 versus a decrease of 10 for those patients who did not receive biologics (p = 0.12). Conclusion: ESS, coupled with AD and ATAD, was successful in the long-term management of the majority of the patients with AERD, which rarely required the incorporation of T2 biologics. Patient questionnaires, such as outcomes measure test score, may identify aspirin therapy failures and help guide the practitioner in deciding when to introduce T2 biologics into the patient's treatment regimen.