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Objective: Malignant otitis externa (MOE) is typically managed with long-term broad-spectrum antibiotics. The impact of surgical intervention on clinical outcomes is not well described. This study aims to compare clinical outcomes of MOE patients managed with or without surgery., Study Design/setting: Retrospective cohort, academic tertiary referral center., Methods: Patients diagnosed with MOE between January 2010 to September 2022 were included. Univariate analyses compared symptoms at initial presentation and long-term (≥1 year) outcomes between surgical and non-surgical patients., Results: A total of 23 patients were included (78% male, mean age 69 ± 13 years, median follow-up 305 days). Most ( N  = 22, 96%) patients were diabetic. Seventeen (74%) underwent surgical intervention (76% tympanomastoidectomy, 24% external auditory canal debridement and biopsy). Poor facial nerve (FN) function at initial presentation (defined as House-Brackmann [HB] grade ≥3) significantly predicted undergoing surgical intervention ( p  = 0.02). Comparing surgically managed versus non-surgical patients at the time of presentation, there were no differences in the degree of hearing loss, severity of diabetes, rate of insulin dependence, incidence of immunosuppression, or the Charlson Comorbidity Index (all p  > 0.05). FN outcomes at long-term follow-up also did not significantly differ (p > 0.05). No significant differences in the length of stay (9 vs. 6 days, p  = 0.2), rate of readmission (31% vs. 17%, p  = 0.5) or 5-year overall survival (53% vs. 66%, p  = 0.6) were observed between surgical and non-surgical patients., Conclusions: Long-term outcomes for patients with MOE remain poor. Patients with poor FN function at presentation were more likely to undergo surgical intervention. Patient comorbidities, including the severity of diabetes, were not predictive of undergoing surgery. However, surgical intervention for MOE did not appear to lower the length of stay, the rate of hospital readmission, or overall mortality in our cohort., Level of Evidence: III., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Importance: Outcomes for patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiation therapy (CRT) have improved with adjuvant immune checkpoint inhibitors, with a reported 5-year overall survival benefit of approximately 10% for adjuvant durvalumab vs placebo after completion of CRT without progression and with preserved performance status. Starting atezolizumab prior to CRT may allow more patients to benefit from immunotherapy., Objective: To evaluate clinical outcomes of patients treated with atezolizumab before and after CRT for unresectable stage III NSCLC., Design, Setting, and Participants: This single-cohort, phase II, nonrandomized controlled trial was conducted at 11 US sites. Patients with pathologically confirmed, unresectable stage III NSCLC who were treatment naive and had good performance status were enrolled between January 3, 2018, and July 24, 2019. Data were locked on March 21, 2023., Interventions: Patients received four 21-day cycles of atezolizumab, 1200 mg intravenously, with therapy administered on day 1 of each cycle. Patients not experiencing tumor progression continued to CRT (60 Gy to involved fields) concurrent with weekly carboplatin area under the curve of 2 and paclitaxel, 50 mg/m2, followed by planned consolidation carboplatin area under the curve of 6 and paclitaxel, 200 mg/m2, for two 21-day cycles. Patients not experiencing progression continued atezolizumab, 1200 mg, every 21 days to complete 1 year of therapy., Main Outcomes and Measures: The primary end point was the disease control rate at 12 weeks. Secondary end points were progression-free survival, overall survival, overall response rate, safety, and translational science end points., Results: A total of 62 patients (median [range] age, 63.9 [38.1-86.5] years; 32 female [51.6%]) were enrolled and received at least 1 dose of atezolizumab. The disease control rate at 12 weeks was 74.2% (80% CI, 65.7%-81.4%). Median progression-free survival was 30.0 months (95% CI, 15.8 to not evaluable), and the median overall survival was not reached. The overall survival rate at 24 months was 73.7% (95% CI, 63.4%-85.7%), and the overall response rate was 66.2%. Seventeen patients (27.4%) experienced grade 3 or higher immune-related adverse events, including 1 with grade 5 pneumonitis and 1 with grade 4 Guillain-Barré syndrome. Thirty patients (48.4%) experienced grade 3 or higher treatment-related adverse events., Conclusions and Relevance: These findings suggest that neoadjuvant atezolizumab merits further study based on safety and encouraging outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT03102242.

The use of endovascular, percutaneous interventions to treat cardiac, arterial, and venous pathologies is becoming increasingly common in medical practice. While endovascular device placement typically carries a low risk, device migration remains a persistent problem with these procedures for which anesthesia providers must have a high index of suspicion. Anesthesia providers should be aware of the wide range of indications for such devices, potential migration locations, and hemodynamic consequences of both the inciting pathology and device migration so they can safely care for patients in these settings. This article aims to discuss a case series of five different device migration events, review the literature surrounding the migration of each device, and propose unique anesthetic considerations as well as a systematic approach by which to approach these complications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Bioengineered tracheal grafts are a potential solution for the repair of long-segment tracheal defects. A recent advancement is partially decellularized tracheal grafts (PDTGs) which enable regeneration of host epithelium and retain viable donor chondrocytes for hypothesized benefits to mechanical properties. We propose a novel and tunable 3D-printed bioreactor for creating large animal PDTG that brings this technology closer to the bedside., Methods: Conventional agitated immersion with surfactant and enzymatic activity was used to partially decellularize New Zealand white rabbit ( Oryctolagus cuniculus ) tracheal segments ( n  = 3). In parallel, tracheal segments ( n  = 3) were decellularized in the bioreactor with continuous extraluminal flow of medium and alternating intraluminal flow of surfactant and medium. Unprocessed tracheal segments ( n  = 3) were also collected as a control. The grafts were assessed using the H&E stain, tissue DNA content, live/dead assay, Masson's trichrome stain, and mechanical testing., Results: Conventional processing required 10 h to achieve decellularization of the epithelium and submucosa with poor chondrocyte viability and mechanical strength. Using the bioreactor reduced processing time by 6 h and resulted in chondrocyte viability and mechanical strength similar to that of native trachea., Conclusion: Large animal PDTG created using our novel 3D printed bioreactor is a promising approach to efficiently produce tracheal grafts. The bioreactor offers flexibility and adjustability favorable to creating PDTG for clinical research and use. Future research includes optimizing flow conditions and transplantation to assess post-implant regeneration and mechanical properties., Level of Evidence: NA., Competing Interests: A provisional patent application titled “Modular Adjustable Bioreactor for Decellularization and Cell Seeding” is described in US Provisional Application No. 63/384028 filed in the United States Patent and Trademark Office on November 16, 2022. Tendy Chiang, Woo Yul Byun, and Lumei Liu share equal inventorship., (© 2024 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

There is currently no suitable autologous tissue to bridge large tracheal defects. As a result, no standard of care exists for long-segment tracheal reconstruction. Tissue engineering has the potential to create a scaffold from allografts or xenografts that can support neotissue regeneration identical to the native trachea. Recent advances in tissue engineering have led to the idea of partial decellularization that allows for the creation of tracheal scaffolds that supports tracheal epithelial formation while preserving mechanical properties. However, the ability of partial decellularization to eliminate graft immunogenicity remains unknown, and understanding the immunogenic properties of partially decellularized tracheal grafts (PDTG) is a critical step toward clinical translation. Here, we determined that tracheal allograft immunogenicity results in epithelial cell sloughing and replacement with dysplastic columnar epithelium and that partial decellularization creates grafts that are able to support an epithelium without histologic signs of rejection. Moreover, allograft implantation elicits CD8+ T-cell infiltration, a mediator of rejection, while PDTG did not. Hence, we establish that partial decellularization eliminates allograft immunogenicity while creating a scaffold for implantation that can support spatially appropriate airway regeneration., Competing Interests: The authors have no conflicts of interest to disclose as described by the American Journal of Transplantation., (© 2023 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of The American Institute of Chemical Engineers.)

In an ongoing, open-label, single-arm phase II study ( NCT02927301 ), 181 patients with untreated, resectable, stage IB-IIIB non-small cell lung cancer received two doses of neoadjuvant atezolizumab monotherapy. The primary end point was major pathological response (MPR; ≤10% viable malignant cells) in resected tumors without EGFR or ALK alterations. Of the 143 patients in the primary end point analysis, the MPR was 20% (95% confidence interval, 14-28%). With a minimum duration of follow-up of 3 years, the 3-year survival rate of 80% was encouraging. The most common adverse events during the neoadjuvant phase were fatigue (39%, 71 of 181) and procedural pain (29%, 53 of 181), along with expected immune-related toxicities; there were no unexpected safety signals. In exploratory analyses, MPR was predicted using the pre-treatment peripheral blood immunophenotype based on 14 immune cell subsets. Immune cell subsets predictive of MPR in the peripheral blood were also identified in the tumor microenvironment and were associated with MPR. This study of neoadjuvant atezolizumab in a large cohort of patients with resectable non-small cell lung cancer was safe and met its primary end point of MPR ≥ 15%. Data from this single-arm, non-randomized trial suggest that profiles of innate immune cells in pre-treatment peripheral blood may predict pathological response after neoadjuvant atezolizumab, but additional studies are needed to determine whether these profiles can inform patient selection and new therapeutic approaches., (© 2022. The Author(s).)

Advancements in personalized medicine have increased the demand for quantity and preservation of tissue architecture of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples. These demands may be addressed by the SonoTip TopGain ® needle, which has a 3-point crown-cut design that contrasts with the standard single bevel design of the ViziShot 2 ® . The objective was to compare the SonoTip TopGain ® and ViziShot 2 ® needles by considering biopsy sample characteristics, diagnostic accuracy, and patient safety. The primary endpoint of the study was the number of high-power fields (HPFs) in the center of the formalin-fixed paraffin-embedded cell block per sample. The lymph node with the highest probability for malignant infiltration based on size and sonographic appearance was chosen as the target lymph node for 20 patients. The same lymph node in each patient was sampled using both the ViziShot 2 ® and SonoTip TopGain ® needles. The samples were measured, sliced, and analyzed by a pathologist. Sixteen patients were biopsied with both needles. Four patients could not be biopsied with the SonoTip TopGain ® needle since it could not penetrate cartilage or be repositioned to bypass cartilage. HPFs and sample dimensions were significantly greater in the patients where sampling with the SonoTip TopGain ® needle was possible ( p = 0.007 and p = 0.005, respectively). Diagnostic accuracy and safety profiles were comparable. Significantly more material can be sampled using the SonoTip TopGain ® needle when cartilage penetration can be avoided. This improves the yield for molecular workup in the era of personalized medicine.

Here we present a miniaturized analog of a blinking human eye to reverse engineer the complexity of the interface between the ocular system and the external environment. Our model comprises human cells and provides unique capabilities to replicate multiscale structural organization, biological phenotypes and dynamically regulated environmental homeostasis of the human ocular surface. Using this biomimetic system, we discovered new biological effects of blink-induced mechanical forces. Furthermore, we developed a specialized in vitro model of evaporative dry-eye disease for high-content drug screening. This work advances our ability to emulate how human physiological systems interface with the external world, and may contribute to the future development of novel screening platforms for biopharmaceutical and environmental applications.

Proteins have gained increasing success as therapeutic agents; however, challenges exist in effective and efficient delivery. In this work, we present a simple and versatile method for encapsulating proteins via complex coacervation with oppositely charged polypeptides, poly(l-lysine) (PLys) and poly(d/l-glutamic acid) (PGlu). A model protein system, bovine serum albumin (BSA), was incorporated efficiently into coacervate droplets via electrostatic interaction up to a maximum loading of one BSA per PLys/PGlu pair and could be released under conditions of decreasing pH. Additionally, encapsulation within complex coacervates did not alter the secondary structure of the protein. Lastly the complex coacervate system was shown to be biocompatible and interact well with cells in vitro. A simple, modular system for encapsulation such as the one presented here may be useful in a range of drug delivery applications.