Ki Wan (Roy) Park

All Publications

• Nano Approaches to Nucleic Acid Delivery: Barriers, Solutions, and Current Landscape. Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology Gonzalez, J. C., Park, K. W., Evans, D. B., Sharma, R., Sahaym, O., Gopalakrishnan, S., Dar, A. I., Valdez, T. A., Sharma, A. 2025; 17 (2): e70010

  Abstract

  Nucleic acid (NA) therapy holds tremendous potential for treating a wide range of genetic diseases by the delivery of therapeutic genes into target cells. However, significant challenges exist in safely and effectively delivering these genes to their intended locations. Viral vectors, though efficient, pose risks such as immunogenicity and mutagenesis. This has resulted in growing interest in non-viral, nanoparticle-based NA delivery systems. This review article describes various physiological barriers to NA delivery and explores nanoparticle-based NA delivery systems, including bioengineered nanoparticles, peptides, lipid nanoparticles, and polymeric nanoparticles, highlighting their unique features to overcome in vivo barriers for NA delivery. While these nanoparticle-based NA delivery systems offer a promising alternative to viral vectors, challenges related to cytotoxicity, reproducible synthesis, and cost need to be addressed. The current clinical landscape of NA delivery is also discussed, emphasizing the need for safer, scalable, and cost-effective solutions. Nanoparticles represent a promising future in NA therapy, with the possibility of developing clinically relevant, non-toxic, stable, and non-immunogenic delivery vehicles, paving the way for broader therapeutic applications and improved clinical outcomes.

  View details for DOI 10.1002/wnan.70010

  View details for PubMedID 40223402

  View details for PubMedCentralID PMC11994986

• Injectable alginate/collagen clindamycin hydrogel for treatment of surgical site infections. Scientific reports Park, R. K., Kim, S., An, J., Lee, M. C., Yang, Y. P., Valdez, T. A. 2025; 15 (1): 7964

  Abstract

  The current standard treatment for surgical site infections (SSIs) is marked by prolonged courses of antibiotics, which have limitations due to antibiotic resistance, systemic side effects, and poor patient adherence. We developed a novel injectable alginate/collagen clindamycin hydrogel that rapidly solidifies upon injection and allows for initial burst release followed by sustained release to maintain therapeutic levels. The rheological, morphological, and in-vitro release kinetics of the hydrogel were characterized. Furthermore, with an in-vivo murine SSI model incubated with logarithmic growth phase 1 × 105 CFU Staphylococcus aureus, one time treatment with injectable hydrogel containing 8 mg clindamycin successfully treated SSI comparable to a cumulative systemic antibiotic dose of 42 mg clindamycin. In an implant SSI model, two-time treatment with the injectable clindamycin antibiotic (16 mg total) successfully suppressed infection and prevented recalcitrant infection. To date, no group has developed a clindamycin encapsulated injectable alginate/collagen hydrogel for the treatment of infection. This tunable hydrogel may serve as an effective delivery vehicle for clinical applications in treating SSIs compared to conventionally available treatments.

  View details for DOI 10.1038/s41598-025-92294-0

  View details for PubMedID 40055420

  View details for PubMedCentralID 9974080

• Mixed-Layered Glycodendrimer Probe for Imaging Inflammation at Surgical Site Infections. ACS sensors Dhull, A., Park, K. W., Dar, A. I., Wang, A., Rani, A., Sharma, R., Valdez, T. A., Sharma, A. 2025

  Abstract

  Surgical site infections (SSIs) remain the most common cause for readmission following surgery and are associated with significant medical comorbidities. Distinguishing between inflammation and early infection postsurgery is a critical challenge for clinicians. Intraoperative surgical debridement of infectious tissues relies heavily on the surgeon's experience, risking error due to difficulty in distinguishing infection from inflammation. We evaluated the simultaneous use of two fluorescent probes, maltotriose-indocyanine-green (ICG-DBCO-maltotriose) and a mixed-layered 2-deoxyglucose dendrimer (2DG-D) labeled with cyanine 5 (2DG-D-Cy5), to delineate between SSI and inflammation in vitro in cell-bacteria coculture and in vivo in an early implant SSI model via multiplexed short-wave infrared (SWIR) imaging. To our knowledge, this study is the first to use multiple fluorescent dyes combined with small molecules and dendrimer-based nanoprobes to differentiate between inflammation and infection within the same experimental model. We synthesized 2DG-D using a convergent method, simplifying synthesis and purification. 2DG-D-Cy5 exclusively labeled the macrophages associated with inflammation in vitro. In vivo SWIR imaging using both probes in a murine implant infection model successfully distinguished infection from inflammation in real time, allowing targeted surgical debridement. This real-time detection of infection and inflammation may enhance diagnostic confidence and aid in the monitoring of therapeutic responses.

  View details for DOI 10.1021/acssensors.4c03544

  View details for PubMedID 40020085

• An mRNA Display Approach for Covalent Targeting of a Staphylococcus aureus Virulence Factor. Journal of the American Chemical Society Wang, S., Woods, E. C., Jo, J., Zhu, J., Hansel-Harris, A., Holcomb, M., Llanos, M., Pedowitz, N. J., Upadhyay, T., Bennett, J., Fellner, M., Park, K. W., Zhang, A., Valdez, T. A., Forli, S., Chan, A. I., Cunningham, C. N., Bogyo, M. 2025

  Abstract

  Staphylococcus aureus (S. aureus) is an opportunistic human pathogen that causes over one million deaths around the world each year. We recently identified a family of serine hydrolases termed fluorophosphonate binding hydrolases (Fphs) that play important roles in lipid metabolism and colonization of a host. Because many of these enzymes are only expressed in Staphylococcus bacteria, they are valuable targets for diagnostics and therapeutics. Here, we developed and screened highly diverse cyclic peptide libraries using mRNA display with a genetically encoded oxadiazolone (Ox) electrophile that was previously shown to potently and covalently inhibit multiple Fph enzymes. By performing multiple rounds of counter selections with WT and catalytic dead FphB, we were able to tune the selectivity of the resulting selected cyclic peptides containing the Ox residue toward the active site serine. From our mRNA display hits, we developed potent and selective fluorescent probes that label the active site of FphB at single digit nanomolar concentrations in live S. aureus bacteria. Taken together, this work demonstrates the potential of using direct genetically encoded electrophiles for mRNA display of covalent binding ligands and identifies potent new probes for FphB that have the potential to be used for diagnostic and therapeutic applications.

  View details for DOI 10.1021/jacs.4c15713

  View details for PubMedID 40013487

• Intraoperative nerve imaging with sodium fluorescein. medRxiv : the preprint server for health sciences Park, R. K., Arús, B. A., Lee, J. Y., Weitzenberg, M. M., Lee, M. C., Nyaeme, M. S., Barthel, J., Balsamo, G., Baik, F. M., Speirs, K., Blume, B., Heller-Algazi, M., Chmyrov, A., Plettenburg, O., Megwalu, U. C., Weitz, J., Distler, M., Bruns, O. T., Valdez, T. A. 2025

  Abstract

  Nerve damage during surgery is a common and serious complication, often leading to chronic pain, functional impairments, and diminished quality of life. However, existing methods for intraoperative nerve identification remain insufficient, especially for detecting small or hidden nerve branches. Here we present a new application of a clinically approved fluorescent agent, sodium fluorescein, to enhance nerve visualization during surgery. Utilizing both clinical and customized imaging systems, fluorescein remarkably improved nerve contrast, revealing structures undetectable with white light, including small branches embedded within tissues. With its established safety profile, low cost, and immediate clinical applicability, sodium fluorescein offers the potential to revolutionize surgical practice by minimizing nerve injuries and improving patient outcomes. Clinical Trial Registration: NCT06054178 .

  View details for DOI 10.1101/2025.02.08.25321923

  View details for PubMedID 40034788

  View details for PubMedCentralID PMC11875269

• An mRNA Display Approach for Covalent Targeting of a Staphylococcus aureus Virulence Factor. bioRxiv : the preprint server for biology Wang, S., Woods, E. C., Jo, J., Zhu, J., Hansel-Harris, A., Holcomb, M., Pedowitz, N. J., Upadhyay, T., Bennett, J., Fellner, M., Park, K. W., Zhang, A., Valdez, T. A., Forli, S., Chan, A. I., Cunningham, C. N., Bogyo, M. 2024

  Abstract

  Staphylococcus aureus (S. aureus) is an opportunistic human pathogen that causes over one million deaths around the world each year. We recently identified a family of serine hydrolases termed fluorophosphonate binding hydrolases (Fphs) that play important roles in lipid metabolism and colonization of a host. Because many of these enzymes are only expressed in Staphylococcus bacteria, they are valuable targets for diagnostics and therapeutics. Here we developed and screened highly diverse cyclic peptide libraries using mRNA display with a genetically encoded oxadiazolone (Ox) electrophile that was previously shown to potently and covalently inhibit multiple Fph enzymes. By performing multiple rounds of counter selections with WT and catalytic dead FphB, we were able to tune the selectivity of the resulting selected cyclic peptides containing the Ox residue towards the desired target. From our mRNA display hits, we developed potent and selective fluorescent probes that label the active site of FphB at single digit nanomolar concentrations in live S. aureus bacteria. Taken together, this work demonstrates the potential of using direct genetically encoded electrophiles for mRNA display of covalent binding ligands and identifies potent new probes for FphB that have the potential to be used for diagnostic and therapeutic applications.

  View details for DOI 10.1101/2024.11.06.622387

  View details for PubMedID 39574702

  View details for PubMedCentralID PMC11581011

• Artificial Intelligence Tracking of Otologic Instruments in Mastoidectomy Videos. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Liu, G. S., Parulekar, S., Lee, M. C., El Chemaly, T., Diop, M., Park, R., Blevins, N. H. 2024

  Abstract

  Develop an artificial intelligence (AI) model to track otologic instruments in mastoidectomy videos.Retrospective case series.Tertiary care center.Six otolaryngology residents (PGY 3-5) and one senior neurotology attending.Thirteen 30-minute videos of cadaveric mastoidectomies were recorded by residents. The suction irrigator and drill were semi-manually annotated. Videos were split into training (N = 8), validation (N = 3), and test (N = 2) sets. YOLOv8, a state-of-the-art AI computer vision model, was adapted to track the instruments.Precision, recall, and mean average precision using an intersection over union cutoff of 50% (mAP50). Drill speed in two prospectively collected live mastoidectomy videos by a resident and attending surgeon.The model achieved excellent performance for tracking the drill (precision 0.93, recall 0.89, and mAP50 0.93) and low performance for the suction irrigator (precision 0.67, recall 0.61, and mAP50 0.62) in test videos. Prediction speed was fast (~100 milliseconds per image). Predictions on prospective videos revealed higher mean drill speed (8.6 ± 5.7 versus 7.6 ± 7.4 mm/s, respectively; mean ± SD; p < 0.01) and duration of high drill speed (>15 mm/s; p < 0.05) in attending than resident surgery.An AI model can track the drill in mastoidectomy videos with high accuracy and near-real-time processing speed. Automated tracking opens the door to analyzing objective metrics of surgical skill without the need for manual annotation and will provide valuable data for future navigation and augmented reality surgical environments.

  View details for DOI 10.1097/MAO.0000000000004330

  View details for PubMedID 39473329

• Artificial Intelligence in Facial Plastics and Reconstructive Surgery. Otolaryngologic clinics of North America Park, K. W., Diop, M., Willens, S. H., Pepper, J. P. 2024

  Abstract

  Artificial intelligence (AI), particularly computer vision and large language models, will impact facial plastic and reconstructive surgery (FPRS) by enhancing diagnostic accuracy, refining surgical planning, and improving post-operative evaluations. These advancements can address subjective limitations of aesthetic surgery by providing objective tools for patient evaluation. Despite these advancements, AI in FPRS has yet to be fully integrated in the clinic setting and faces numerous challenges including algorithmic bias, ethical considerations, and need for validation. This article discusses current and emerging AI technologies in FPRS for the clinic setting, providing a glimpse of its future potential.

  View details for DOI 10.1016/j.otc.2024.05.002

  View details for PubMedID 38971626

• Polymer-Tethered Quenched Fluorescent Probes for Enhanced Imaging of Tumor-Associated Proteases. ACS sensors Hadzima, M., Faucher, F. F., Blažková, K., Yim, J. J., Guerra, M., Chen, S., Woods, E. C., Park, K. W., Šácha, P., Šubr, V., Kostka, L., Etrych, T., Majer, P., Konvalinka, J., Bogyo, M. 2024

  Abstract

  Fluorescence-based contrast agents enable real-time detection of solid tumors and their neovasculature, making them ideal for use in image-guided surgery. Several agents have entered late-stage clinical trials or secured FDA approval, suggesting they are likely to become the standard of care in cancer surgeries. One of the key parameters to optimize in contrast agents is molecular size, which dictates much of the pharmacokinetic and pharmacodynamic properties of the agent. Here, we describe the development of a class of protease-activated quenched fluorescent probes in which a N-(2-hydroxypropyl)methacrylamide copolymer is used as the primary scaffold. This copolymer core provides a high degree of probe modularity to generate structures that cannot be achieved with small molecules and peptide probes. We used a previously validated cathepsin substrate and evaluated the effects of length and type of linker, as well as the positioning of the fluorophore/quencher pair on the polymer core. We found that the polymeric probes could be optimized to achieve increased overall signal and tumor-to-background ratios compared to the reference small molecule probe. Our results also revealed multiple structure-activity relationship trends that can be used to design and optimize future optical imaging probes. Furthermore, they confirm that a hydrophilic polymer is an ideal scaffold for use in optical imaging contrast probes, allowing a highly modular design that enables efficient optimization to maximize probe accumulation and overall biodistribution properties.

  View details for DOI 10.1021/acssensors.4c00912

  View details for PubMedID 38941307

• Development of Oxadiazolone Activity-Based Probes Targeting FphE for Specific Detection of Staphylococcus aureus Infections. Journal of the American Chemical Society Jo, J., Upadhyay, T., Woods, E. C., Park, K. W., Pedowitz, N. J., Jaworek-Korjakowska, J., Wang, S., Valdez, T. A., Fellner, M., Bogyo, M. 2024

  Abstract

  Staphylococcus aureus (S. aureus) is a major human pathogen that is responsible for a wide range of systemic infections. Since its propensity to form biofilms in vivo poses formidable challenges for both detection and treatment, tools that can be used to specifically image S. aureus biofilms are highly valuable for clinical management. Here, we describe the development of oxadiazolone-based activity-based probes to target the S. aureus-specific serine hydrolase FphE. Because this enzyme lacks homologues in other bacteria, it is an ideal target for selective imaging of S. aureus infections. Using X-ray crystallography, direct cell labeling, and mouse models of infection, we demonstrate that oxadiazolone-based probes enable specific labeling of S. aureus bacteria through the direct covalent modification of the FphE active site serine. These results demonstrate the utility of the oxadizolone electrophile for activity-based probes and validate FphE as a target for the development of imaging contrast agents for the rapid detection of S. aureus infections.

  View details for DOI 10.1021/jacs.3c13974

  View details for PubMedID 38411555

• Risk Factors Associated with Postoperative CSF Leak in Extrasellar Tumors. Journal of neurological surgery. Part B, Skull base Zhang, H., Peeters, S., Vengorivich, G., Antoury, L., Park, K. W., Wells, C., Suh, J. D., Lee, J. T., Heaney, A., Bergsneider, M., Kim, W., Wang, M. B. 2024; 85 (1): 15-20

  Abstract

  Objective  While postoperative cerebrospinal fluid (CSF) leak rates of pituitary tumors have been frequently studied, there are fewer studies examining postoperative CSF leak rates for extrasellar tumors. The purpose of this study was to identify risk factors for the development of postoperative CSF leak in patients undergoing endoscopic surgery for extrasellar tumors. Methods  A retrospective chart review was done for patients who underwent endoscopic resection for extrasellar tumors between 2008 and 2020. Age, gender, tumor type, tumor location, tumor size, reconstruction technique, medical comorbidities, and other potential risk factors were identified. Data was analyzed to identify significant risk factors for development of postoperative CSF leak. Results  There were 100 patients with extrasellar tumors who developed intraoperative CSF leaks. Seventeen patients (17%) developed postoperative CSF leaks. Leaks occurred at a median of 2 days following surgery (range 0-34 days). Clival tumors had a significantly higher incidence of postoperative leak than those in other sites ( p  < 0.05). There were no significant differences in other locations, body mass index, tumor size, reconstruction technique, medical comorbidities, or other factors. There were nearly twice as many intraoperative grade III leaks in those who developed postoperative CSF leak, but this was not statistically significant ( p  = 0.12). Conclusion  Extrasellar tumors, particularly clival tumors, have a higher rate of postoperative CSF leak than pituitary tumors. Prophylactic lumbar drains can be considered for patients at high risk for developing postoperative CSF leak.

  View details for DOI 10.1055/s-0042-1760355

  View details for PubMedID 38274484

  View details for PubMedCentralID PMC10807959

• Current and Emerging Therapies for Chronic Subjective Tinnitus. Journal of clinical medicine Park, K. W., Kullar, P., Malhotra, C., Stankovic, K. M. 2023; 12 (20)

  Abstract

  Chronic subjective tinnitus, the perception of sound without an external source for longer than six months, may be a greatly debilitating condition for some people, and is associated with psychiatric comorbidities and high healthcare costs. Current treatments are not beneficial for all patients and there is a large need for new therapies for tinnitus.Unlike rarer cases of objective tinnitus, chronic subjective tinnitus often has no obvious etiology and a diverse pathophysiology. In the absence of objective testing, diagnosis is heavily based on clinical assessment. Management strategies include hearing aids, sound masking, tinnitus retraining therapy, cognitive behavioral therapy, and emerging therapies including transcranial magnetic stimulation and electrical stimulation.Although current treatments are limited, emerging diagnostics and treatments provide promising avenues for the management of tinnitus symptoms.

  View details for DOI 10.3390/jcm12206555

  View details for PubMedID 37892692

  View details for PubMedCentralID PMC10607630

• International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System. Journal of neurological surgery. Part B, Skull base Lechner, M., Takahashi, Y., Turri-Zanoni, M., Ferrari, M., Liu, J., Counsell, N., Mattavelli, D., Rampinelli, V., Vermi, W., Lombardi, D., Saade, R., Park, K. W., Schartinger, V. H., Franchi, A., Facco, C., Sessa, F., Battocchio, S., Fenton, T. R., Vaz, F. M., O'Flynn, P., Howard, D., Stimpson, P., Wang, S., Hannan, S. A., Unadkat, S., Hughes, J., Dwivedi, R., Forde, C. T., Randhawa, P., Gane, S., Joseph, J., Andrews, P. J., Dave, M., Fleming, J. C., Thomson, D., Zhu, T., Teschendorff, A., Royle, G., Steele, C., Jimenez, J. E., Laco, J., Wang, E. W., Snyderman, C., Lacy, P. D., Woods, R., O'Neill, J. P., Saraswathula, A., Kaur, R. P., Zhao, T., Ramanathan, M., Gallia, G. L., London, N. R., Le, Q. T., West, R. B., Patel, Z. M., Nayak, J. V., Hwang, P. H., Hermsen, M., Llorente, J., Facchetti, F., Nicolai, P., Bossi, P., Castelnuovo, P., Jay, A., Carnell, D., Forster, M. D., Bell, D. M., Lund, V. J., Hanna, E. Y. 2023; 84 (4): 307-319

  Abstract

  Objectives  Sinonasal mucosal melanoma (SNMM) is an extremely rare and challenging sinonasal malignancy with a poor prognosis. Standard treatment involves complete surgical resection, but the role of adjuvant therapy remains unclear. Crucially, our understanding of its clinical presentation, course, and optimal treatment remains limited, and few advancements in improving its management have been made in the recent past. Methods  We conducted an international multicenter retrospective analysis of 505 SNMM cases from 11 institutions across the United States, United Kingdom, Ireland, and continental Europe. Data on clinical presentation, diagnosis, treatment, and clinical outcomes were assessed. Results  One-, three-, and five-year recurrence-free and overall survival were 61.4, 30.6, and 22.0%, and 77.6, 49.2, and 38.3%, respectively. Compared with disease confined to the nasal cavity, sinus involvement confers significantly worse survival; based on this, further stratifying the T3 stage was highly prognostic ( p  < 0.001) with implications for a potential modification to the current TNM staging system. There was a statistically significant survival benefit for patients who received adjuvant radiotherapy, compared with those who underwent surgery alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI]: 0.57-0.96, p  = 0.021). Immune checkpoint blockade for the management of recurrent or persistent disease, with or without distant metastasis, conferred longer survival (HR = 0.50, 95% CI: 0.25-1.00, p  = 0.036). Conclusions  We present findings from the largest cohort of SNMM reported to date. We demonstrate the potential utility of further stratifying the T3 stage by sinus involvement and present promising data on the benefit of immune checkpoint inhibitors for recurrent, persistent, or metastatic disease with implications for future clinical trials in this field.

  View details for DOI 10.1055/s-0042-1750178

  View details for PubMedID 37405239

  View details for PubMedCentralID PMC10317567

• Is lobectomy sufficient for multifocal papillary thyroid microcarcinoma? American journal of otolaryngology Park, K. W., Han, A. Y., Kim, C. M., Wang, M. B., Nguyen, C. T. 2023; 44 (4): 103881

  Abstract

  Multifocal papillary thyroid microcarcinoma (PTMC) has been associated with a higher incidence of lymph node involvement, bilateral involvement, and extrathyroidal extension compared to unifocal papillary thyroid cancer (PTC).To describe the incidence and determinants of survival for patients with multifocal PTMC using the Surveillance, Epidemiology, and End Result (SEER) database.The SEER registry was utilized to calculate survival trends for patients with PTMC between 2010 and 2015. Patient data was then analyzed with respect to age, sex, race, multifocality, and types of surgery rendered.Overall Survival (OS) and Disease Specific Survival (DSS).22,283 cases of papillary thyroid microcarcinoma (T1a N0 M0) were identified. The cohort was composed of 82.6 % females, and about 82 % of patients were of white race. The mean age at diagnosis was 51.9 years. Multifocal PTMC was present in 32.2 % of the tumors (n = 7186). 73.9 % of patients underwent total thyroidectomy and 23.0 % received lobectomy. OS at 2 and 5 years was 98 % and 95 %, respectively. Multivariate analysis revealed that age, sex, and multifocality were determinants of OS. Only age was a determinant of DSS. Kaplan-Meier survival analysis revealed that multifocal PTMC had similar mean OS between lobectomy and total thyroidectomy patients (69.59 months versus 69.82 months).PTMC has a good prognosis. Our analysis revealed that age was a determinant of OS and DSS; sex and multifocality were also prognosticators for OS. The type of surgery, whether lobectomy or total thyroidectomy, was not a determinant of survival in multifocal PTMC.

  View details for DOI 10.1016/j.amjoto.2023.103881

  View details for PubMedID 37031520

• International Multicenter Study of Clinical Outcomes of Sinonasal Melanoma Shows Survival Benefit for Patients Treated with Immune Checkpoint Inhibitors and Potential Improvements to the Current TNM Staging System JOURNAL OF NEUROLOGICAL SURGERY PART B-SKULL BASE Lechner, M., Takahashi, Y., Turri-Zanoni, M., Ferrari, M., Liu, J., Counsell, N., Mattavelli, D., Rampinelli, V., Vermi, W., Lombardi, D., Saade, R., Park, K., Schartinger, V. H., Franchi, A., Facco, C., Sessa, F., Battocchio, S., Fenton, T. R., Vaz, F. M., O'Flynn, P., Howard, D., Stimpson, P., Wang, S., Hannan, S., Unadkat, S., Hughes, J., Dwivedi, R., Forde, C. T., Randhawa, P., Gane, S., Joseph, J., Andrews, P. J., Dave, M., Fleming, J. C., Thomson, D., Zhu, T., Teschendorff, A., Royle, G., Steele, C., Jimenez, J. E., Laco, J., Wang, E. W., Snyderman, C., Lacy, P. D., Woods, R., O'Neill, J. P., Saraswathula, A., Kaur, R., Zhao, T., Ramanathan, M., Gallia, G. L., London, N. R., Le, Q., West, R. B., Patel, Z. M., Nayak, J. V., Hwang, P. H., Hermsen, M., Llorente, J., Facchetti, F., Nicolai, P., Bossi, P., Castelnuovo, P., Jay, A., Carnell, D., Forster, M. D., Bell, D. M., Lund, V. J., Hanna, E. Y. 2022

  View details for DOI 10.1055/s-0042-1750178

  View details for Web of Science ID 000822748800001

• Clinical outcomes, Kadish-INSICA staging and therapeutic targeting of somatostatin receptor 2 in olfactory neuroblastoma. European journal of cancer (Oxford, England : 1990) Lechner, M., Takahashi, Y., Turri-Zanoni, M., Liu, J., Counsell, N., Hermsen, M., Kaur, R. P., Zhao, T., Ramanathan, M. J., Schartinger, V. H., Emanuel, O., Helman, S., Varghese, J., Dudas, J., Riechelmann, H., Sprung, S., Haybaeck, J., Howard, D., Engel, N. W., Stewart, S., Brooks, L., Pickles, J. C., Jacques, T. S., Fenton, T. R., Williams, L., Vaz, F. M., O'Flynn, P., Stimpson, P., Wang, S., Hannan, S. A., Unadkat, S., Hughes, J., Dwivedi, R., Forde, C. T., Randhawa, P., Gane, S., Joseph, J., Andrews, P. J., Royle, G., Franchi, A., Maragliano, R., Battocchio, S., Bewicke-Copley, H., Pipinikas, C., Webster, A., Thirlwell, C., Ho, D., Teschendorff, A., Zhu, T., Steele, C. D., Pillay, N., Vanhaesebroeck, B., Mohyeldin, A., Fernandez-Miranda, J., Park, K. W., Le, Q., West, R. B., Saade, R., Manes, R. P., Omay, S. B., Vining, E. M., Judson, B. L., Yarbrough, W. G., Sansovini, M., Silvia, N., Grassi, I., Bongiovanni, A., Capper, D., Schuller, U., Thavaraj, S., Sandison, A., Surda, P., Hopkins, C., Ferrari, M., Mattavelli, D., Rampinelli, V., Facchetti, F., Nicolai, P., Bossi, P., Henriquez, O. A., Magliocca, K., Solares, C. A., Wise, S. K., Llorente, J. L., Patel, Z. M., Nayak, J. V., Hwang, P. H., Lacy, P. D., Woods, R., O'Neill, J. P., Jay, A., Carnell, D., Forster, M. D., Ishii, M., London, N. R., Bell, D. M., Gallia, G. L., Castelnuovo, P., Severi, S., Lund, V. J., Hanna, E. Y. 1800

  Abstract

  INTRODUCTION: Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy.METHODS: We conducted a retrospective analysis of 404 primary, locally recurrent, and metastatic olfactory neuroblastoma (ONB) patients from 12 institutions in the United States of America, United Kingdom and Europe. Clinicopathological characteristics and treatment approach were evaluated. SSTR2 expression, SSTR2-targeted imaging and the efficacy of peptide receptor radionuclide therapy [PRRT](177Lu-DOTATATE) were reported in a subset of our cohort (LUTHREE trial; NCT03454763).RESULTS: Dural infiltration at presentation was a significant predictor of overall survival (OS) and disease-free survival (DFS) in primary cases (n=278). Kadish-Morita staging and Dulguerov T-stage both had limitations regarding their prognostic value. Multivariable survival analysis demonstrated improved outcomes with lower stage and receipt of adjuvant radiotherapy. Prophylactic neck irradiation significantly reduces the rate of nodal recurrence. 82.4% of the cohort were positive for SSTR2; treatment of three metastatic cases with SSTR2-targeted peptide-radionuclide receptor therapy (PRRT) in the LUTHREE trial was well-tolerated and resulted in stable disease (SD).CONCLUSIONS: This study presents pertinent clinical data from the largest dataset, to date, on ONB. We identify key prognostic markers and integrate these into an updated staging system, highlight the importance of adjuvant radiotherapy across all disease stages, the utility of prophylactic neck irradiation and the potential efficacy of targeting SSTR2 to manage disease.

  View details for DOI 10.1016/j.ejca.2021.09.046

  View details for PubMedID 34980502

• Round Cell Sarcoma with EWSR1-PATZ1 Gene Fusion in the Neck: Case Report and Review of the Literature. The Laryngoscope Park, K. W., Cai, Y., Benjamin, T., Qorbani, A., George, J. 2020; 130 (12): E833-E836

  Abstract

  EWSR1-PATZ1 is a rare gene fusion recently recognized to occur in round and spindle cell sarcomas. To date, fewer than 20 cases have been described in the literature. However, no dedicated case reports have detailed its presentation in the head and neck region. We recently cared for a 52-year-old woman with an isolated, single right level 5A cervical mass. Excisional biopsy at an external hospital revealed pathology results consistent with EWSR1-PATZ1 polyphenotypic round and spindle cell sarcoma. The patient subsequently underwent surgical excision of the tumor and right neck lymph node dissection followed by adjuvant chemoradiation. Laryngoscope, 2020.

  View details for DOI 10.1002/lary.28554

  View details for PubMedID 32134119

• Retrospective Analysis of Patients With Acute Invasive Fungal Rhinosinusitis in a Single Tertiary Academic Medical Center: A 10-Year Experience. American journal of rhinology & allergy Vengerovich, G., Echanique, K. A., Park, K. W., Wells, C., Suh, J. D., Lee, J. T., Wang, M. B. 2020; 34 (3): 324-330

  View details for DOI 10.1177/1945892419896233

  View details for PubMedID 31852212

• Contrast-Induced Sialadenitis of the Sublingual Glands. Case reports in otolaryngology Park, K. W., Han, A. Y., Kim, C. M., Tam, K., Chhetri, D. K. 2020; 2020: 8851382

  Abstract

  Contrast-induced sialadenitis (CIS) is a rare, delayed pseudoallergic reaction from iodine containing contrast. Previously reported cases of CIS demonstrated that the two major salivary glands (parotid and submandibular) can be affected. The initial encounter of this entity can raise alarms to physicians as the differential diagnoses include serious infectious and inflammatory conditions such as Ludwig's angina and angioedema. Subsequently, it may lead to unnecessary testing and increased healthcare cost. Here we present a 60-year-old male who presented with bilateral sublingual gland swelling following exposure to iodinated contrast. With timely diagnosis by the otolaryngologist, the patient received conservative management that led to a full resolution within a few days. To date, this is the first case of CIS only involving the sublingual glands. We conclude that CIS can involve any of the major salivary glands.

  View details for DOI 10.1155/2020/8851382

  View details for PubMedID 32963864

• Readmissions after endoscopic skull base surgery: associated risk factors and prevention. International forum of allergy & rhinology Vengerovich, G., Park, K. W., Antoury, L., Wells, C., Suh, J. D., Lee, J. T., Heaney, A. P., Bergsneider, M., Wang, M. B. 2020; 10 (1): 110-113

  Abstract

  Unplanned readmissions within 30 days of discharge is a quality measure introduced by the Centers for Medicare Services. This measure has been used to rate hospital quality and also to penalize hospitals for excess readmissions. It has been hypothesized that shorter hospital stays and fewer readmissions are associated with endoscopic skull base procedures. In this study we analyze endoscopic skull base procedures performed at our institution over a 10-year period to identify rates and factors associated with readmissions after endoscopic skull base surgery.A retrospective chart review was performed at a tertiary care academic medical center identifying patients who underwent endoscopic skull base surgery over the past 10 years. Data on patient demographics and tumor variables, as well as patient variables such as body mass index (BMI), revision surgery, history of skull base radiation, medical comorbidities, intraoperative cerebrospinal fluid (CSF) leaks, and postoperative CSF leaks, were recorded.Eight hundred thirty-three patients were included in our study. Sixty-one patients (7.3%) were readmitted a total of 66 times within 30 days. The most common reasons were as follows: hyponatremia (n = 18); CSF leak (n = 17); epistaxis (n = 3); diabetes insipidus (n = 3); rhinorrhea (n = 3); as well as other reasons. Statistical analysis revealed that the presence of intraoperative CSF leak was the only statistically significant variable associated with increased rate of readmissions within 30 days of discharge (p < 0.001).Presence of intraoperative CSF leak was the only statistically significant variable associated with an increased risk for readmission after surgery. Other tumor and patient variables were not associated with an increased risk of readmission within 30 days.

  View details for DOI 10.1002/alr.22453

  View details for PubMedID 31589814

• Financial implications of telemedicine visits in an academic endocrine surgery program. Surgery Zheng, F., Park, K. W., Thi, W. J., Ro, C. C., Bass, B. L., Yeh, M. W. 2019; 165 (3): 617-621

  Abstract

  Telemedicine is an emerging medium for the delivery of ambulatory care, but the reimbursement profile of telemedicine visits in the surgical setting has not been well studied.A retrospective assessment of telemedicine encounters for thyroid and parathyroid conditions occurring from April 2015 to April 2017 was performed. Financial reimbursement from commercial payers for new and established patient visits were compared between telemedicine visits and in-person visits. Patient "savings" in terms of travel distance and drive time were calculated.A total of 290 telemedicine encounters were conducted; 7% were initial consultations, 47% were postoperative visits, and 45% were follow-up visits. The median patient age was 57 years. The median round-trip travel distance saved was 123.6 miles with estimated drive time of 2.4 hours per encounter. In 2% of cases, a second in-person visit within the 90-day global period occurred after a postoperative telemedicine encounter. Charges were filed for 67 encounters. The initial unpaid claims rate was 6%, which was consistent with the unpaid claims rate for in-person visits. The charge-to-collection ratio was comparable to that of in-person visits. There was a higher ratio of level 2 visits in the telemedicine encounters. Over the study period, 70 clinic hours were liberated via the use of telemedicine.Endocrine surgery telemedicine visits have the same level for level reimbursement profile as in-person visits. Down-coding and elimination of components of in-office physical examinations may lead to modest decreases in overall reimbursement. Other advantages include reallocation of clinic resources and decreased travel burden for patients.

  View details for DOI 10.1016/j.surg.2018.08.017

  View details for PubMedID 30245125

• Decreasing Use of Radioactive Iodine for Low-Risk Thyroid Cancer in California, 1999 to 2015. The Journal of clinical endocrinology and metabolism Park, K. W., Wu, J. X., Du, L., Leung, A. M., Yeh, M. W., Livhits, M. J. 2018; 103 (3): 1095-1101

  Abstract

  Routine radioactive iodine (RAI) ablation for low-risk differentiated thyroid cancer (DTC) is not supported by current practice guidelines.To assess recent stage-specific trends in use of RAI ablation.Retrospective study of patients with DTC (1999 to 2015) identified from the California Cancer Registry. Statistical analysis included standardized differences, P values, and multivariable analyses using RAI as the predictor variable.Trends and drivers of RAI ablation for low-risk DTC.Of 46,906 patients with DTC who underwent near-total or total thyroidectomy [mean age 48.2 ± 15.5 (standard deviation) years, 77% female), 25,457 (54%) received RAI. The proportion of patients with regional/distant disease who received RAI remained stable at 68%. Use of RAI for patients with localized disease (no extrathyroidal extension, lymph node, or distant metastases) decreased from 55% (1999) to 30% (2015), with the most substantial change occurring in tumors <1 cm (39% to 11%). The rate also decreased for localized tumors between 1 and 2 cm (62% to 34%) and 2 and 4 cm (67% to 49%) and remained stable at 59% for tumors >4 cm. In multivariable analyses, patients with localized disease were less likely to receive RAI if they were >65 years old [odds ratio (OR) 0.77, 95% confidence interval (CI): 0.71 to 0.83], had tumors <1 cm (OR 0.33, 95% CI: 0.31 to 0.35), or were treated in an academic hospital (OR 0.71, 95% CI: 0.67 to 0.75).The rate of RAI ablation decreased over time, mainly attributable to decreased use for localized DTCs <2 cm. Many patients with low-risk DTC still receive RAI unnecessarily.

  View details for DOI 10.1210/jc.2017-02269

  View details for PubMedID 29267880

• Intraventricular and interventricular cellular heterogeneity of inotropic responses to α(1)-adrenergic stimulation. American journal of physiology. Heart and circulatory physiology Chu, C., Thai, K., Park, K. W., Wang, P., Makwana, O., Lovett, D. H., Simpson, P. C., Baker, A. J. 2013; 304 (7): H946-53

  Abstract

  α1-Adrenergic receptors (α1-ARs) elicit a negative inotropic effect (NIE) in the mouse right ventricular (RV) myocardium but a positive inotropic effect (PIE) in the left ventricular (LV) myocardium. Effects on myofilament Ca(2+) sensitivity play a role, but effects on Ca(2+) handling could also contribute. We monitored the effects of α1-AR stimulation on contraction and Ca(2+) transients using single myocytes isolated from the RV or LV. Interestingly, for both the RV and LV, we found heterogeneous myocyte inotropic responses. α1-ARs mediated either a PIE or NIE, although RV myocytes had a greater proportion of cells manifesting a NIE (68%) compared with LV myocytes (36%). Stimulation of a single α1-AR subtype (α1A-ARs) with a subtype-selective agonist also elicited heterogeneous inotropic responses, suggesting that the heterogeneity arose from events downstream of the α1A-AR subtype. For RV and LV myocytes, an α1-AR-mediated PIE was associated with an increased Ca(2+) transient and a NIE was associated with a decreased Ca(2+) transient, suggesting a key role for Ca(2+) handling. For RV and LV myocytes, α1-AR-mediated decreases in the Ca(2+) transient were associated with increased Ca(2+) export from the cell and decreased Ca(2+) content of the sarcoplasmic reticulum. In contrast, for myocytes with α1-AR-induced increased Ca(2+) transients, sarcoplasmic reticulum Ca(2+) content was not increased, suggesting that other mechanisms contributed to the increased Ca(2+) transients. This study demonstrates the marked heterogeneity of LV and RV cellular inotropic responses to stimulation of α1-ARs and reveals a new aspect of biological heterogeneity among myocytes in the regulation of contraction.

  View details for DOI 10.1152/ajpheart.00822.2012

  View details for PubMedID 23355341

  View details for PubMedCentralID PMC3625891