All Publications


  • Impact of Histologic Risk Factors on Recurrence Rates for Oral Cavity Squamous Cell Carcinoma. The Annals of otology, rhinology, and laryngology Kligerman, M. P., Moon, P. K., Tusty, M., Cloutier, J. M., Ma, Y., Holsinger, C. F., Divi, V. 2022: 34894221111223

    Abstract

    This study assesses the impact of adverse histologic risk factors including worst pattern of invasion (WPOI), predominant pattern of invasion (PPOI), tumor budding, and tumor infiltrating lymphocytes (TILS), on risk of recurrence in patients with early-stage Oral Cavity Squamous Cell Carcinoma (OCSCC).Retrospective chart review was performed at a single institution to identify patients with OCSCC who underwent surgical excision. Inclusion criteria included T1-T2 stage disease based on AJCC seventh edition guidelines, no cervical lymph node involvement, no perineural invasion (PNI), no lymphovascular invasion (LVI), no post-operative adjuvant radiation therapy, and cancer involving only the oral tongue or floor of mouth. Patients were excluded if they had positive final margins. A subset of 35 patients were selected for additional histologic review to determine WPOI, PPOI, TB, and TILS. Bivariable and multivariable cox analysis were performed to determine variables associated with recurrence.One hundred and sixty-one patients met criteria and were included in the analysis. Variables that were significantly associated with recurrence on bivariable analysis included tumors with high risk PPOI (groups 4 and 5; P = .021), TB with 10 or more buds (P = .021), T-stage (P = .001), neck dissection (P = .03), and depth of invasion (DOI) >4 mm (P = .044). Multivariable cox proportional hazards found T-stage (HR: 6.40; 95% CI 1.67, 24.50; P = .007), neck dissection (HR: 0.23; 95% CI 0.07, 0.82; P = .023), and TBs (HR: 1.17; 95% CI 1.05, 1.30; P = .006) to be most predictive of recurrence.TB is a strong predictor of recurrence. WPOI, PPOI, and TILS were not statistically significant risk factors for recurrence.

    View details for DOI 10.1177/00034894221111223

    View details for PubMedID 35899590

  • Head and Neck Cancer Among Native Hawaiian and Other Pacific Islander Patients-Disparities in Cancer Stage at Presentation and Survival Outcomes Compared With Other Races: A Population-Based Cohort Study. JAMA otolaryngology-- head & neck surgery Moon, P. K., Ma, Y., Megwalu, U. C. 2022

    Abstract

    Importance: Research studies often group Native Hawaiian and Other Pacific Islander individuals together with Asian individuals despite being consistently identified as having worse health outcomes and higher rates of comorbidities and mortality. Native Hawaiian and Other Pacific Islander individuals also have high incidence rates of oral cavity and pharyngeal cancer compared with the general population; however, disparities in clinical presentation and survival outcomes of head and neck cancer squamous cell carcinoma (HNSCC) among this population have not been investigated nor compared with those of other races.Objective: To determine the association of race with cancer stage at diagnosis and survival outcomes among Native Hawaiian and Other Pacific Islander patients with HNSCC compared with Asian and non-Hispanic White patients.Design, Setting, and Participants: This was a retrospective population-based cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) 18 database. Asian, Native Hawaiian or Other Pacific Islander, and non-Hispanic White adult patients diagnosed in 1988 through 2015 with HNSCC of the oral cavity, oropharynx, nasopharynx, larynx, and hypopharynx were included; any patient whose record was missing data on disease or demographic information was excluded.Main Outcomes and Measures: Cancer stage at presentation was compared among Asian, Native Hawaiian and Other Pacific Islander, and non-Hispanic White patients using a multivariable logistic regression model. Survival outcomes were compared among these racial groups using Cox regression models. Data analyses were performed from July 1, 2021, to March 20, 2022.Results: The total study population comprised 76 473 patients: 4894 Asian (mean [SD] age at presentation, 60.7 [14.6] years), 469 Native Hawaiian and Other Pacific Islander (57.8 [12.3] years), and 71 110 non-Hispanic White (62.2 [12.1] years) individuals. Native Hawaiian and Other Pacific Islander patients were more likely to present with advanced-stage HNSCC (odds ratio [OR] 1.38; 95% CI, 1.12 -1.72) compared with non-Hispanic White patients. Asian patients presented with similar stage disease (OR, 1.04; 95% CI, 0.97-1.11) compared with non-Hispanic White patients. Native Hawaiian and Other Pacific Islander patients had worse disease-specific survival (HR, 1.18; 95% CI, 1.02-1.36) compared with non-Hispanic White patients after adjusting for clinical and demographic factors. In contrast, Asian patients had improved disease-specific survival (HR, 0.93; 95% CI, 0.88-0.98) compared with non-Hispanic White patients.Conclusions and Relevance: This retrospective population-based cohort study suggests that Native Hawaiian and Other Pacific Islander race was associated with more advanced HNSCC, and worse disease-specific survival compared with non-Hispanic White race, while Asian race was associated with improved survival. This study highlights the importance of disaggregating Asian from Pacific Islander data when assessing health disparities, and the need for culturally sensitive interventions to promote earlier detection of head and neck cancer and improved survival among the Native Hawaiian and Other Pacific Islander population.

    View details for DOI 10.1001/jamaoto.2022.1086

    View details for PubMedID 35616952

  • Infectious Complications Following Cochlear Implant: Risk Factors, Natural History, and Management Patterns. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Moon, P. K., Qian, Z. J., Ahmad, I. N., Stankovic, K. M., Chang, K. W., Cheng, A. G. 2022: 1945998221082530

    Abstract

    OBJECTIVE: To describe the natural history, detail the treatment patterns, and identify the risk factors for cochlear implant (CI) infections in a large US cohort.STUDY DESIGN: Retrospective study based on insurance claims.SETTING: Optum Data Mart database: 6101 patients who received CIs from 2003 to 2019.METHODS: Infections, treatments patterns, and timelines were described. A multivariable logistic regression model was used to assess the association between postoperative oral antibiotics and CI infection.RESULTS: The cohort includes 4736 (77.6%) adults and 1365 (22.4%) children. Between adult and pediatric patients, rates of CI infection (5.1% vs 4.5%, P = .18) and explantation (1.2% vs 0.8%, P = .11) were not significantly different. Infections typically occurred within 5 months of surgery. Children were diagnosed with CI infection earlier than adults (median difference, -1.5 months; P = .001). Postoperative oral antibiotic supply was not associated with lower risk of CI infection in either children or adults. However, among adults, otitis media was associated with higher odds of CI infection (odds ratio, 1.41; P < .001), while higher income was associated with lower odds of CI infection (odds ratio, 0.71; P = .03).CONCLUSIONS: Postoperative oral antibiotics were not associated with lower risk of infection or interventions. Otitis media episodes and lower income were associated with increased risk of infection among adults as well as intervention overall. Infection typically presented within the first 6 months after surgery, with children presenting earlier than adults. Overall, our findings serve as a resource for providers to consider in their care of patients with CIs.

    View details for DOI 10.1177/01945998221082530

    View details for PubMedID 35192408

  • Thyroid Cancer Incidence and Mortality Trends in the United States: 2000 - 2018. Thyroid : official journal of the American Thyroid Association Megwalu, U., Moon, P. K. 2022

    Abstract

    BACKGROUND: Thyroid cancer incidence has significantly increased in the United States over the past few decades. Recent studies have suggested a change in thyroid cancer incidence trends following 2013. The objective of this study was to update the data on thyroid cancer incidence and mortality trends in the US.METHODS: Thyroid cancer incidence and incidence-based mortality trends were evaluated using the Surveillance, Epidemiology, and End Results-18 cancer registry. Cases of thyroid cancer diagnosed in 2000-2018, and thyroid cancer deaths during 2000-2018 were included. Annual percent change (APC) was calculated using joinpoint regression analysis.RESULTS: Among 197,070 patients, female (75.6%) and white (81.0%) patients comprised the majority of cases. Papillary thyroid carcinoma (PTC) was the most common histology (89.1%). Incidence rates increased during 2000 - 2009 (APC 6.80, 95% CI 6.46 to 7.13) and 2009-2014 (APC 2.58, 95% CI 1.71 to 3.47), then decreased during 2014-2018 (APC -2.33, 95% CI -3.15 to -1.51). The incidence trends for PTC overall, localized disease, and tumors ≤ 1.0 cm mirrored the overall thyroid cancer trends, while incidence rates for regional disease stabilized during 2015-2018 (APC -1.65, 95% CI -4.09 to 0.84). The incidence of distant disease decreased during 2015-2018 (APC (APC -17.86, 95% CI -26.47 to -8.25). The incidence of tumors ≤ 1.0 cm decreased (APC -5.83, 95% CI -7.24 to -4.40), while the incidence of tumors 1.1 - 2.0 cm (APC -0.10, 95% CI -1.16 to 0.96), 2.1 - 4.0 cm (APC 1.12, 95% CI -0.17 to 2.43), and > 4.0 cm (APC -1.13, 95% CI -4.58 to 2.45) stabilized during the most recent 4 - 6 years. Incidence-based mortality increased throughout 2000-2018 (average APC 1.35, 95% CI 0.88 to 1.82).CONCLUSION: Thyroid cancer incidence rates have declined since 2014. Similar declines are noted for PTC, localized disease, and tumors ≤ 1.0 cm, but not for tumors > 2.0 cm. Incidence-based mortality rates continue to increase. These findings suggest that changing patterns in the management of thyroid nodules may have led to a decrease in diagnosis of small indolent tumors, but not more advanced tumors.

    View details for DOI 10.1089/thy.2021.0662

    View details for PubMedID 35132899

  • Early Onset Diffusion Abnormalities in Refractory Headache Disorders. Frontiers in neurology Santoro, J. D., Moon, P. K., Han, M., McKenna, E. S., Tong, E., MacEachern, S. J., Forkert, N. D., Yeom, K. W. 2022; 13: 898219

    Abstract

    Objective: This study sought to determine if individuals with medically refractory migraine headache have volume or diffusion abnormalities on neuroimaging compared to neurotypical individuals.Background: Neuroimaging biomarkers in headache medicine continue to be limited. Early prediction of medically refractory headache and migraine disorders could result in earlier administration of high efficacy therapeutics.Methods: A single-center, retrospective, case control study was performed. All patients were evaluated clinically between 2014 and 2018. Individuals with medically refractory migraine headache (defined by ICDH-3 criteria) without any other chronic medical diseases were enrolled. Patients had to have failed more than two therapeutics and aura was not exclusionary. The initial MRI study for each patient was reviewed. Multiple brain regions were analyzed for volume and apparent diffusion coefficient values. These were compared to 81 neurotypical control patients.Results: A total of 79 patients with medically refractory migraine headache were included and compared to 74 neurotypical controls without headache disorders. Time between clinical diagnosis and neuroimaging was a median of 24 months (IQR: 12.0-37.0). Comparison of individuals with medically refractory migraine headache to controls revealed statistically significant differences in median apparent diffusion coefficient (ADC) in multiple brain subregions (p < 0.001). Post-hoc pair-wise analysis comparing individuals with medically refractory migraine headache to control patients revealed significantly decreased median ADC values for the thalamus, caudate, putamen, pallidum, amygdala, brainstem, and cerebral white matter. No volumetric differences were observed between groups.Conclusions: In individuals with medically refractory MH, ADC changes are measurable in multiple brain structures at an early age, prior to the failure of multiple pharmacologic interventions and the diagnosis of medically refractory MH. This data supports the hypothesis that structural connectivity issues may predispose some patients toward more medically refractory pain disorders such as MH.

    View details for DOI 10.3389/fneur.2022.898219

    View details for PubMedID 35775057

  • Thyroid Cancer Incidence Trends Among Filipinos in the United States. The Laryngoscope Megwalu, U. C., Osazuwa-Peters, N., Moon, P., Palaniappan, L. P. 1800

    Abstract

    OBJECTIVE: To analyze thyroid cancer incidence trends among Filipinos relative to non-Filipino Asians and non-Hispanic Whites in the US.STUDY DESIGN: Population-based analysis of cancer incidence data.METHODS: Population-based analysis of cancer incidence data from Surveillance, Epidemiology, and End Results 9 detailed Asian/Pacific Islander subgroup incidence and population datasets. Adult patients aged 20 and older with thyroid cancer diagnosed in 2004 to 2014 were included. Annual percent change (APC) of the incidence rates were calculated using joinpoint regression analysis.RESULTS: The incidence rates were 19.57 (95% CI 19.03-20.12) per 100,000 for Filipinos, 10.45 (95% CI 10.22-10.68) per 100,000 for non-Filipino Asians, and 13.94 (95% CI 13.85-14.02) per 100,000 for non-Hispanic Whites. The highest increase was seen among non-Hispanic Whites (average APC 5.04, 95% CI 4.61-5.46). Incidence rates of tumors≤2cm remained stable among Filipinos but increased in non-Filipino Asians (average APC 5.38, 95% CI 2.51-8.34) and non-Hispanic Whites (average APC 5.81 95% CI 4.52-7.11).CONCLUSION: Filipinos have high incidence of thyroid cancer compared with other racial/ethnic groups. However, non-Hispanic Whites have the highest increase in incidence rates, resulting in a significant narrowing of the gap in incidence rates between Filipinos and non-Hispanic Whites. This is most likely due to enhanced detection of small tumors in non-Hispanic Whites. Laryngoscope, 2021.

    View details for DOI 10.1002/lary.29986

    View details for PubMedID 34910822

  • MRI Correlates of Ototoxicity in the Auditory Pathway in Children Treated for Medulloblastoma. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Moon, P., Theruvath, J., Chang, J., Song, Y., Shpanskaya, K., Maleki, M., Cheng, A. G., Ahmad, I. N., Yeom, K. W. 2021

    Abstract

    OBJECTIVE: To assess diffusion and perfusion changes of the auditory pathway in pediatric medulloblastoma patients exposed to ototoxic therapies.STUDY DESIGN: Retrospective cohort study.SETTING: A single academic tertiary children's hospital.PATIENTS: Twenty pediatric medulloblastoma patients (13 men; mean age 12.0 ± 4.8 yr) treated with platinum-based chemotherapy with or without radiation and 18 age-and-sex matched controls were included. Ototoxicity scores were determined using Chang Ototoxicity Grading Scale.INTERVENTIONS: Three Tesla magnetic resonance was used for diffusion tensor and arterial spin labeling perfusion imaging.MAIN OUTCOME MEASURES: Quantitative diffusion tensor metrics were extracted from the Heschl's gyrus, auditory radiation, and inferior colliculus. Arterial spin labeling perfusion of the Heschl's gyrus was also examined.RESULTS: Nine patients had clinically significant hearing loss, or Chang grades more than or equal to 2a; 11 patients had mild/no hearing loss, or Chang grades less than 2a. The clinically significant hearing loss group showed reduced mean diffusivity in the Heschl's gyrus (p = 0.018) and auditory radiation (p = 0.037), and decreased perfusion in the Heschl's gyrus (p = 0.001). Mild/no hearing loss group showed reduced mean diffusivity (p = 0.036) in Heschl's gyrus only, with a decrease in perfusion (p = 0.008). There were no differences between groups in the inferior colliculus. There was no difference in fractional anisotropy between patients exposed to ototoxic therapies and controls.CONCLUSIONS: Patients exposed to ototoxic therapies demonstrated microstructural and physiological alteration of the auditory pathway. The present study shows proof-of-concept use of diffusion tensor imaging to gauge ototoxicity along the auditory pathway. Future larger cohort studies are needed to assess significance of changes in diffusion tensor imaging longitudinally, and the relationship between these changes and hearing loss severity and longitudinal changes of the developing auditory white matter.

    View details for DOI 10.1097/MAO.0000000000003336

    View details for PubMedID 34739428

  • Restoring metabolism of myeloid cells reverses cognitive decline in ageing. Nature Minhas, P. S., Latif-Hernandez, A., McReynolds, M. R., Durairaj, A. S., Wang, Q., Rubin, A., Joshi, A. U., He, J. Q., Gauba, E., Liu, L., Wang, C., Linde, M., Sugiura, Y., Moon, P. K., Majeti, R., Suematsu, M., Mochly-Rosen, D., Weissman, I. L., Longo, F. M., Rabinowitz, J. D., Andreasson, K. I. 2021

    Abstract

    Ageing is characterized by the development of persistent pro-inflammatory responses that contribute to atherosclerosis, metabolic syndrome, cancer and frailty1-3. The ageing brain is also vulnerable to inflammation, as demonstrated by the high prevalence of age-associated cognitive decline and Alzheimer's disease4-6. Systemically, circulating pro-inflammatory factors can promote cognitive decline7,8, and in the brain, microglia lose the ability to clear misfolded proteins that are associated with neurodegeneration9,10. However, the underlying mechanisms that initiate and sustain maladaptive inflammation with ageing are not well defined. Here we show that in ageing mice myeloid cell bioenergetics are suppressed in response to increased signalling by the lipid messenger prostaglandin E2 (PGE2), a major modulator of inflammation11. In ageing macrophages and microglia, PGE2 signalling through its EP2 receptor promotes the sequestration of glucose into glycogen, reducing glucose flux and mitochondrial respiration. This energy-deficient state, which drives maladaptive pro-inflammatory responses, is further augmented by a dependence of aged myeloid cells on glucose as a principal fuel source. In aged mice, inhibition of myeloid EP2 signalling rejuvenates cellular bioenergetics, systemic and brain inflammatory states, hippocampal synaptic plasticity and spatial memory. Moreover, blockade of peripheral myeloid EP2 signalling is sufficient to restore cognition in aged mice. Our study suggests that cognitive ageing is not a static or irrevocable condition but can be reversed by reprogramming myeloid glucose metabolism to restore youthful immune functions.

    View details for DOI 10.1038/s41586-020-03160-0

    View details for PubMedID 33473210

  • Parotid gland incidentalomas: A single-institution experience. American journal of otolaryngology Moon, P. K., Tusty, M., Megwalu, U. C. 2021; 43 (2): 103296

    Abstract

    Parotid gland incidentaloma (PGI) management has not been well characterized in the literature. This study assesses clinicopathologic features, initial evaluation, management, and outcomes of PGIs discovered on various imaging modalities.This is a retrospective case series from a single academic institution. The study cohort included 34 patients with parotid gland incidentalomas discovered between January 2009 and December 2019.Parotid gland incidentalomas were most frequently identified on magnetic resonance imaging (16 patients, 47.1%). Most patients (26 patients, 76.5%) underwent further evaluation with subsequent imaging, most often magnetic resonance imaging (18 patients, 69.2%), and fine needle aspiration biopsy (33 patients, 97.1%). Most tumors were benign on fine needle aspiration biopsy (19 patients, 57.6%). Most cases (21 patients, 61.8%) were managed with observation without parotidectomy. Malignant findings on fine needle aspiration cytology were associated with increased likelihood of undergoing parotidectomy (25% vs 0%; p = 0.04). Among the patients who received a parotidectomy, most (8 patients, 61.5%) had benign findings on final histopathology.Parotid gland incidentalomas were discovered across a diverse set of imaging modalities in our institution. Magnetic resonance imaging and fine needle aspiration were often performed for further evaluation. Most cases were found to be benign on fine needle aspiration and were managed with observation. These findings highlight the necessity of appropriate work-up for these tumors, and the need for shared decision making between the patient and the physician in selecting the appropriate treatment strategy.

    View details for DOI 10.1016/j.amjoto.2021.103296

    View details for PubMedID 34894452

  • Cerebral volume and diffusion MRI changes in children with sensorineural hearing loss. NeuroImage. Clinical Moon, P. K., Qian, J. Z., McKenna, E. n., Xi, K. n., Rowe, N. C., Ng, N. N., Zheng, J. n., Tam, L. T., MacEachern, S. J., Ahmad, I. n., Cheng, A. G., Forkert, N. D., Yeom, K. W. 2020; 27: 102328

    Abstract

    Sensorineural hearing loss (SNHL) is the most prevalent congenital sensory deficit in children. Information regarding underlying brain microstructure could offer insight into neural development in deaf children and potentially guide therapies that optimize language development. We sought to quantitatively evaluate MRI-based cerebral volume and gray matter microstructure children with SNHL.We conducted a retrospective study of children with SNHL who obtained brain MRI at 3 T. The study cohort comprised 63 children with congenital SNHL without known focal brain lesion or structural abnormality (33 males; mean age 5.3 years; age range 1 to 11.8 years) and 64 age-matched controls without neurological, developmental, or MRI-based brain macrostructure abnormality. An atlas-based analysis was used to extract quantitative volume and median diffusivity (ADC) in the following brain regions: cerebral cortex, thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens, brain stem, and cerebral white matter. SNHL patients were further stratified by severity scores and hearing loss etiology.Children with SNHL showed higher median ADC of the cortex (p = .019), thalamus (p < .001), caudate (p = .005), and brainstem (p = .003) and smaller brainstem volumes (p = .007) compared to controls. Patients with profound bilateral SNHL did not show any significant differences compared to patients with milder bilateral SNHL, but both cohorts independently had smaller brainstem volumes compared to controls. Children with unilateral SNHL showed greater amygdala volumes compared to controls (p = .021), but no differences were found comparing unilateral SNHL to bilateral SNHL. Based on etiology for SNHL, patients with Pendrin mutations showed higher ADC values in the brainstem (p = .029, respectively); patients with Connexin 26 showed higher ADC values in both the thalamus (p < .001) and brainstem (p < .001) compared to controls.SNHL patients showed significant differences in diffusion and volume in brain subregions, with region-specific findings for patients with Connexin 26 and Pendrin mutations. Future longitudinal studies could examine macro- and microstructure changes in children with SNHL over development and potential predictive role for MRI after interventions including cochlear implant outcome.

    View details for DOI 10.1016/j.nicl.2020.102328

    View details for PubMedID 32622314

  • Association of Pediatric Acute-Onset Neuropsychiatric Syndrome With Microstructural Differences in Brain Regions Detected via Diffusion-Weighted Magnetic Resonance Imaging JAMA Network Open Zheng, J., Frankovich, J., McKenna, E. S., Rowe, N. C., MacEachern, S. J., Ng, N. N., Tam, L. T., Moon, P. K., Gao, J., Thienemann, M., Forkert, N. D., Yeom, K. W. 2020
  • Significance of Nodal Metastasis in Parotid Gland Acinar Cell Carcinoma The Laryngoscope Moon*, P. K., Tusty*, M., Divi, V., Megwalu, U. C. 2020

    View details for DOI 10.1002/lary.28966

  • Revisiting IDO and its value as a predictive marker for anti-PD-1 resistance JOURNAL OF TRANSLATIONAL MEDICINE Moon, P., Tran, S., Minhas, P. 2019; 17
  • Macrophage de novo NAD(+) synthesis specifies immune function in aging and inflammation NATURE IMMUNOLOGY Minhas, P. S., Liu, L., Moon, P. K., Joshi, A. U., Dove, C., Mhatre, S., Contrepois, K., Wang, Q., Lee, B. A., Coronado, M., Bernstein, D., Snyder, M. P., Migaud, M., Majeti, R., Mochly-Rosen, D., Rabinowitz, J. D., Andreasson, K. I. 2019; 20 (1): 50-+
  • Reexamining IFN-gamma Stimulation of De Novo NAD+ in Monocyte-Derived Macrophages INTERNATIONAL JOURNAL OF TRYPTOPHAN RESEARCH Moon, P., Minhas, P. 2018; 11
  • Reevaluating the role of IDO1: Examining NAD+ metabolism in inflammation Journal of Neuroimmunology Moon, P. K., Minhas, P. S. 2017; 307: 31-32
  • Teasing apart NAD(+) metabolism in inflammation: commentary on Zhou et al. (2016). Br J Pharmacol 173: 2352-2368. British journal of pharmacology Moon, P. n., Minhas, P. n. 2017; 174 (3): 281–83

    View details for PubMedID 28092923

    View details for PubMedCentralID PMC5241388