Peter L. Santa Maria, MBBS, PhD

All Publications

• Salvage Microsurgery Following Failed Primary Radiosurgery in Sporadic Vestibular Schwannoma. JAMA otolaryngology-- head & neck surgery Marinelli, J. P., Herberg, H. A., Moore, L. S., Yancey, K. L., Kay-Rivest, E., Casale, G. G., Durham, A., Khandalavala, K. R., Lund-Johansen, M., Kosaraju, N., Lohse, C. M., Patel, N. S., Gurgel, R. K., Babu, S. C., Golfinos, J. G., Roland, J. T., Hunter, J. B., Kutz, J. W., Santa Maria, P. L., Link, M. J., Tveiten, Ø. V., Carlson, M. L. 2024

  Abstract

  Management of sporadic vestibular schwannoma with radiosurgery is becoming increasingly common globally; however, limited data currently characterize patient outcomes in the setting of microsurgical salvage for radiosurgical failure.To describe the clinical outcomes of salvage microsurgery following failed primary stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) among patients with sporadic vestibular schwannoma.This was a cohort study of adults (≥18 years old) with sporadic vestibular schwannoma who underwent salvage microsurgery following failed primary SRS/FSRT in 7 vestibular schwannoma treatment centers across the US and Norway. Data collection was performed between July 2022 and January 2023, with data analysis performed between January and July 2023.Salvage microsurgical tumor resection.Composite outcome of undergoing less than gross total resection (GTR) or experiencing long-term facial paresis.Among 126 patients, the median (IQR) age at time of salvage microsurgery was 62 (53-70) years, 69 (55%) were female, and 113 of 117 (97%) had tumors that extended into the cerebellopontine angle at time of salvage. Of 125 patients, 96 (76%) underwent primary gamma knife SRS, while 24 (19%) underwent linear accelerator-based SRS; the remaining patients underwent FSRT using other modalities. Postoperative cerebrospinal fluid leak was seen in 15 of 126 patients (12%), hydrocephalus in 8 (6%), symptomatic stroke in 7 (6%), and meningitis in 2 (2%). Each 1-mm increase in cerebellopontine angle tumor size was associated with a 13% increased likelihood of foregoing GTR (64 of 102 patients [63%]) or long-term postoperative House-Brackmann grade higher than I (48 of 102 patients [47%]) (odds ratio, 1.13; 95% CI, 1.04-1.23). Following salvage microsurgery, tumor growth-free survival rates at 1, 3, and 5 years were 97% (95% CI, 94%-100%), 93% (95% CI, 87%-99%), and 91% (95% CI, 84%-98%), respectively.In this cohort study, more than half of patients who received salvage microsurgery following primary SRS/FSRT underwent less than GTR or experienced some degree of facial paresis long term. These data suggest that the cumulative risk of developing facial paresis following primary SRS/FSRT by the end of the patient's journey with treatment approximates 2.5% to 7.5% when using published primary SRS/FSRT long-term tumor control rates.

  View details for DOI 10.1001/jamaoto.2023.4474

  View details for PubMedID 38358763

  View details for PubMedCentralID PMC10870221

• SPARKing academic technologies across the valley of death. Nature biotechnology Kim, J. S., Kargotich, S., Lee, S. H., Yajima, R., Garcia, A. A., Ehrenkaufer, G., Romeo, M., Maria, P. S., Grimes, K. V., Mochly-Rosen, D. 2024; 42 (2): 339-342

  View details for DOI 10.1038/s41587-024-02130-5

  View details for PubMedID 38361072

  View details for PubMedCentralID 6226120

• PANEL 3: Otitis media animal models, cell culture, tissue regeneration & pathophysiology. International journal of pediatric otorhinolaryngology Kurabi, A., Dewan, K., Kerschner, J. E., Leichtle, A., Li, J. D., Santa Maria, P. L., Preciado, D. 2023; 176: 111814

  Abstract

  To review and summarize recently published key articles on the topics of animal models, cell culture studies, tissue biomedical engineering and regeneration, and new models in relation to otitis media (OM).Electronic databases: PubMed, National Library of Medicine, Ovid Medline.Key topics were assigned to the panel participants for identification and detailed evaluation. The PubMed reviews were focused on the period from June 2019 to June 2023, in any of the objective subject(s) or keywords listed above, noting the relevant references relating to these advances with a global overview and noting areas of recommendation(s). The final manuscript was prepared with input from all panel members.In conclusion, ex vivo and in vivo OM research models have seen great advancements in the past 4 years. From the usage of novel genetic and molecular tools to the refinement of in vivo inducible and spontaneous mouse models, to the introduction of a wide array of reliable middle ear epithelium (MEE) cell culture systems, the next five years are likely to experience exponential growth in OM pathophysiology discoveries. Moreover, advances in these systems will predictably facilitate rapid means for novel molecular therapeutic studies.

  View details for DOI 10.1016/j.ijporl.2023.111814

  View details for PubMedID 38101097

• Eradication of Bacterial Persister Cells By Leveraging Their Low Metabolic Activity Using Adenosine Triphosphate Coated Gold Nanoclusters. Nano today Bekale, L. A., Sharma, D., Bacacao, B., Chen, J., Santa Maria, P. L. 2023; 51

  Abstract

  Bacteria first develop tolerance after antibiotic exposure; later genetic resistance emerges through the population of tolerant bacteria. Bacterial persister cells are the multidrug-tolerant subpopulation within an isogenic bacteria culture that maintains genetic susceptibility to antibiotics. Because of this link between antibiotic tolerance and resistance and the rise of antibiotic resistance, there is a pressing need to develop treatments to eradicate persister cells. Current anti persister cell strategies are based on the paradigm of "awakening" them from their low metabolic state before attempting eradication with traditional antibiotics. Herein, we demonstrate that the low metabolic activity of persister cells can be exploited for eradication over their metabolically active counterparts. We engineered gold nanoclusters coated with adenosine triphosphate (AuNC@ATP) as a benchmark nanocluster that kills persister cells over exponential growth bacterial cells and prove the feasibility of this new concept. Finally, using AuNC@ATP as a new research tool, we demonstrated that it is possible to prevent the emergence of antibiotic-resistant superbugs with an anti-persister compound. Eradicating persister cells with AuNC@ATP in an isogenic culture of bacteria stops the emergence of superbug bacteria mediated by the sub-lethal dose of conventional antibiotics. Our findings lay the groundwork for developing novel nano-antibiotics targeting persister cells, which promise to prevent the emergence of superbugs and prolong the lifespan of currently available antibiotics.

  View details for DOI 10.1016/j.nantod.2023.101895

  View details for PubMedID 37575958

  View details for PubMedCentralID PMC10421611

• Influence of CX3CR1 Deletion on Cochlear Hair Cell Survival and Macrophage Expression in Chronic Suppurative Otitis Media. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Schiel, V., Xia, A., Santa Maria, P. L. 2023; 44 (6): 605-610

  Abstract

  Our objective was to determine whether the receptor CX3CR1 is necessary for the recruitment of macrophages to the cochlea in chronic suppurative otitis media (CSOM) and if its deletion can prevent hair cell loss in CSOM.CSOM is a neglected disease that afflicts 330 million people worldwide and is the most common cause of permanent hearing loss among children in the developing world. It is characterized by a chronically discharging infected middle ear. We have previously demonstrated that CSOM causes macrophage associated sensory hearing loss. The receptor CX3CR1 is expressed on macrophages, which have been shown to be increased at the time point of outer hair cell (OHC) loss in CSOM.In this report, we examine the influence of CX3CR1 deletion (CX3CR1-/-) in a validated model of Pseudomonas aeruginosa (PA) CSOM.The data show no difference in OHC loss between the CX3CR1-/- CSOM group and CX3CR1+/+ CSOM group (p = 0.28). We observed partial OHC loss in the cochlear basal turn, no OHC loss in the middle and apical turns in both CX3CR1-/- and CX3CR1+/+ CSOM mice at 14 days after bacterial inoculation. No inner hair cell (IHC) loss was found in all cochlear turns in all groups. We also counted F4/80 labeled macrophages in the spiral ganglion, spiral ligament, stria vascularis and spiral limbus of the basal, middle, and apical turn in cryosections. We did not find a significant difference in the total number of cochlear macrophages between CX3CR1-/- mice and CX3CR1+/+ mice (p = 0.97).The data did not support a role for CX3CR1 macrophage associated HC loss in CSOM.

  View details for DOI 10.1097/MAO.0000000000003884

  View details for PubMedID 37315234

  View details for PubMedCentralID PMC10275455

• Eradication of bacterial persister cells by leveraging their low metabolic activity using adenosine triphosphate coated gold nanoclusters NANO TODAY Bekale, L. A., Sharma, D., Bacacao, B., Chen, J., Maria, P. 2023; 51

  View details for DOI 10.1016/j.nantod.2023.101895

  View details for Web of Science ID 001025103400001

• Impact of Cochlear Dose on Hearing Preservation Following Stereotactic Radiosurgery in Treatment of Vestibular Schwannomas: A Multi-center Study. World neurosurgery Chang, S. D., Muacevic, A., Klein, A. L., Sherman, J. H., Romanelli, P., Santa Maria, P. L., Fuerweger, C., Bossi Zanetti, I., Beltramo, G., Vaisbush, Y., Tran, E., Feng, A., Teng, H., Meola, A., Gibbs, I., Tolisano, A. M., Kutz, J. W., Wardak, Z., Nedzi, L. A., Hong, R., MacRae, D., Sohal, P., Kapoor, E., Sabet-Rasekh, P., Maghami, S., Moncada, P. X., Zaleski-King, A., Amdur, R., Monfared, A. 2023

  Abstract

  BACKGROUND: Stereotactic radiosurgery (SRS) is a well-established treatment for vestibular schwannomas (VS). Hearing loss remains a main morbidity of VS and its treatments, including SRS. Effects of radiation parameters of SRS on hearing remain unknown.OBJECTIVES: The goal of this study is to determine the effect of tumor volume, patient demographics, pre-treatment hearing status, cochlear radiation dose, total tumor radiation dose, fractionation, and other radiotherapy parameters on hearing deterioration.METHODS: Multicenter retrospective analysis of 611 patients who underwent SRS for VS from 1990-2020 and had pre- and post-treatment audiograms.RESULTS: Pure tone averages (PTA)s increased and word recognition scores (WRS)s decreased in treated ears at 12-60 months while remaining stable in untreated ears. Higher baseline PTA, higher tumor radiation dose, higher maximum cochlear dose, and usage of single fraction resulted in higher post radiation PTA; WRS was only predicted by baseline WRS and age. Higher baseline PTA, single fraction treatment, higher tumor radiation dose, and higher maximum cochlear dose resulted in a faster deterioration in PTA. Below a maximum cochlear dose of 3 Gy, there were no statistically significant changes in PTA or WRS.CONCLUSION: Decline of hearing at 1 year in VS patients after SRS is directly related to maximum cochlear dose, single versus 3-fraction treatment, total tumor radiation dose, and baseline hearing level. The maximum safe cochlear dose for hearing preservation at 1 year is 3 Gy, and the use of 3 fractions instead of 1 fraction was better at preserving hearing.

  View details for DOI 10.1016/j.wneu.2023.05.098

  View details for PubMedID 37268187

• Bio-Inspired Muco-Adhesive Polymers for Drug Delivery Applications. Polymers Jawadi, Z., Yang, C., Haidar, Z. S., Santa Maria, P. L., Massa, S. 2022; 14 (24)

  Abstract

  Muco-adhesive drug delivery systems continue to be one of the most studied for controlled pharmacokinetics and pharmacodynamics. Briefly, muco-adhesive polymers, can be described as bio-polymers that adhere to the mucosal (mucus) surface layer, for an extended residency period of time at the site of application, by the help of interfacial forces resulting in improved drug delivery. When compared to traditional drug delivery systems, muco-adhesive carriers have the potential to enhance therapeutic performance and efficacy, locally and systematically, in oral, rectal, vaginal, amongst other routes. Yet, the achieving successful muco-adhesion in a novel polymeric drug delivery solution is a complex process involving key physico-chemico-mechanical parameters such as adsorption, wettability, polymer chain length, inter-penetration and cross-linking, to list a few. Hence, and in light of accruing progress, evidence and interest, during the last decade, this review aims to provide the reader with an overview of the theories, principles, properties, and underlying mechanisms of muco-adhesive polymers for pharmaceutics; from basics to design to characterization to optimization to evaluation to market. A special focus is devoted to recent advances incorporating bio-inspired polymers for designing controlled muco-adhesive drug delivery systems.

  View details for DOI 10.3390/polym14245459

  View details for PubMedID 36559825

• Povidone-Iodine Fails to Eradicate Chronic Suppurative Otitis Media and Demonstrates Ototoxic Risk in Mice. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Kaufman, A. C., Bacacao, B. S., Berkay, B., Sharma, D., Mishra, A., O'Toole, G. A., Saunders, J. E., Xia, A., Bekale, L. A., Santa Maria, P. L. 2022

  Abstract

  Commercially available povidone-iodine solution can eliminate biofilms and persister cells rapidly in in vivo achievable concentrations without inducing ototoxicity.Chronic suppurative otitis media (CSOM) is a substantial global problem. Current treatment options often induce a temporary remission without leading to a permanent cessation of symptoms secondary to the treatments' inability to eliminate persister cells. Povidone-iodine has been shown to be able to clear biofilm and planktonic cells in in vitro assays, but there are reports of ototoxic effects limiting its clinical utility.Bacterial and biofilm growth with quantification by spectrophotomer, murine auditory brainstem response (ABR), and distortion product otoacoustic emissions, immunohistochemistry, in vivo povidone-iodine treatment of murine CSOM, persister cell assay.Commercially available 10% povidone-iodine solution is able to completely eradicate multiple clinical strains of Pseudomonas aeruginosa and Staphylococcus aureus in vitro with 10 minutes of exposure. Mice that have received a transtympanic injection of 1% povidone-iodine solution did not have significantly different auditory brainstem response or distortion product otoacoustic emission results compared with the control. Mice that received a povidone-iodine scrub or 10% povidone-iodine solution had significantly worsened hearing (25- and 13-dB increase in threshold, respectively; p < 0.05). In vivo CSOM infection recurred in all mice after the completion of treatment with 10% povidone-iodine solution, and there was no improvement in the bacterial load after treatment, indicating in vivo failure of therapy.Povidone-iodine solution is effective at eliminating biofilm and persister cells in vitro at in vivo achievable concentrations but fails in vivo most likely because of kinetics of distribution in vivo. Even if drug distribution could be improved, the therapeutic window is likely to be too small given that the diluted solution does not have ototoxic potential, whereas while the scrub variant, which contains detergents, and the undiluted solution are ototoxic after a single treatment.

  View details for DOI 10.1097/MAO.0000000000003726

  View details for PubMedID 36240734

• New Medical Device and Therapeutic Approvals in Otolaryngology: State of the Art Review of 2021. OTO open Choi, A. M., Brenner, M. J., Gorelik, D., Erbele, I. D., Crowson, M. G., Kadkade, P., Takashima, M., Santa Maria, P. L., Hong, R. S., Rose, A. S., Ostrander, B. T., Rabbani, C. C., Morrison, R. J., Weissbrod, P. A., Tate, A. D., Kain, J. J., Lina, I. A., Shaffer, S. R., Ahmed, O. G. 2022; 6 (3): 2473974X221126495

  Abstract

  To evaluate new medical devices and drugs pertinent to otolaryngology-head and neck surgery that were approved by the Food and Drug Administration (FDA) in 2021.Publicly available FDA device and drug approvals from ENT (ear, nose, and throat), anesthesia, neurosurgery, plastic surgery, and general surgery FDA committees.FDA device and therapeutic approvals were identified and reviewed by members of the American Academy of Otolaryngology-Head and Neck Surgery's Medical Devices and Drugs Committee. Two independent reviewers assessed the relevance of devices and drugs to otolaryngologists. Medical devices and drugs were then allocated to their respective subspecialty fields for critical review based on available scientific literature.The Medical Devices and Drugs Committee reviewed 1153 devices and 52 novel drugs that received FDA approval in 2021 (67 ENT, 106 anesthesia, 618 general surgery and plastic surgery, 362 neurosurgery). Twenty-three devices and 1 therapeutic agent relevant to otolaryngology were included in the state of the art review. Advances spanned all subspecialties, including over-the-counter hearing aid options in otology, expanding treatment options for rhinitis in rhinology, innovative laser-safe endotracheal tubes in laryngology, novel facial rejuvenation and implant technology in facial plastic surgery, and advances in noninvasive and surgical treatment options for obstructive sleep apnea.FDA approvals for new technology and pharmaceuticals present new opportunities across subspecialties in otolaryngology. Clinicians' nuanced understanding of the safety, advantages, and limitations of these innovations ensures ongoing progress in patient care.

  View details for DOI 10.1177/2473974X221126495

  View details for PubMedID 36171808

  View details for PubMedCentralID PMC9511340

• Chronic suppurative otitis media causes macrophage-associated sensorineural hearing loss. Journal of neuroinflammation Xia, A., Thai, A., Cao, Z., Chen, X., Chen, J., Bacacao, B., Bekale, L. A., Schiel, V., Bollyky, P. L., Maria, P. L. 2022; 19 (1): 224

  Abstract

  BACKGROUND: Chronic suppurative otitis media (CSOM) is the most common cause of permanent hearing loss in children in the developing world. A large component of the permanent hearing loss is sensory in nature and our understanding of the mechanism of this has so far been limited to post-mortem human specimens or acute infection models that are not representative of human CSOM. In this report, we assess cochlear injury in a validated Pseudomonas aeruginosa (PA) CSOM mouse model.METHODS: We generated persisters (PCs) and inoculated them into the mouse middle ear cavity. We tracked infection with IVIS and detected PA using RT-PCR. We assessed cochlear damage and innate immunity by Immunohistochemistry. Finally, we evaluated cytokines with multiplex assay and quantitative real-time PCR.RESULTS: We observed outer hair cell (OHC) loss predominantly in the basal turn of the cochlear at 14days after bacterial inoculation. Macrophages, not neutrophils are the major immune cells in the cochlea in CSOM displaying increased numbers and a distribution correlated with the observed cochlear injury. The progression of the morphological changes suggests a transition from monocytes into tissue macrophages following infection. We also show that PA do not enter the cochlea and live bacteria are required for cochlear injury. We characterized cytokine activity in the CSOM cochlea.CONCLUSIONS: Taken together, this data shows a critical role for macrophages in CSOM-mediated sensorineural hearing loss (SNHL).

  View details for DOI 10.1186/s12974-022-02585-w

  View details for PubMedID 36096817

• Anti-persister and Anti-biofilm Activity of Self-Assembled Antimicrobial Peptoid Ellipsoidal Micelles. ACS infectious diseases Lin, J. S., Bekale, L. A., Molchanova, N., Nielsen, J. E., Wright, M., Bacacao, B., Diamond, G., Jenssen, H., Santa Maria, P. L., Barron, A. E. 2022

  Abstract

  Although persister cells are the root cause of resistance development and relapse of chronic infections, more attention has been focused on developing antimicrobial agents against resistant bacterial strains than on developing anti-persister agents. Frustratingly, the global preclinical antibacterial pipeline does not include any anti-persister drug. Therefore, the central point of this work is to explore antimicrobial peptidomimetics called peptoids (sequence-specific oligo-N-substituted glycines) as a new class of anti-persister drugs. In this study, we demonstrate that one particular antimicrobial peptoid, the sequence-specific pentamer TM5, is active against planktonic persister cells and sterilizes biofilms formed by both Gram-negative and Gram-positive bacteria. Moreover, we demonstrate the potential of TM5 to inhibit cytokine production induced by lipopolysaccharides from Gram-negative bacteria. We anticipate that this work can pave the way to the development of new anti-persister agents based on antimicrobial peptoids of this class to simultaneously help address the crisis of bacterial resistance and reduce the occurrence of the relapse of chronic infections.

  View details for DOI 10.1021/acsinfecdis.2c00288

  View details for PubMedID 36018039

• Gold nanocluster adjuvant enables the eradication of persister cells by antibiotics and abolishes the emergence of resistance. Nanoscale Cao, Z., Chen, X., Chen, J., Xia, A., Bacacao, B., Tran, J., Sharma, D., Bekale, L. A., Santa Maria, P. L. 2022

  Abstract

  Persister cells are responsible for relapses of infections common in cystic fibrosis and chronic suppurative otitis media (CSOM). Yet, there are no Food and Drug Administration (FDA) approved antibiotics to eradicate persister cells. Frustratingly, the global preclinical bacterial pipeline does not contain antibacterial agents targeting persister cells. Therefore, we report a nontraditional antimicrobial chemotherapy strategy based on gold nanoclusters adjuvant to eradicate persister cells by existing antibiotics belonging to that different class. Compared to killing with antibiotics alone, combining antibiotics and AuNC@CPP sterilizes persister cells and biofilms. Enhanced killing of up to 4 orders of magnitude in a validated mouse model of CSOM with Pseudomonas aeruginosa infection was observed when combining antibiotics and AuNC@CPP, informing a potential approach to improve the treatment of CSOM. We established that the mechanism of action of AuNC@CPP is due to disruption of the proton gradient and membrane hyperpolarization. The method presented here could compensate for the lack of new antibiotics to combat persister cells. This method could also benefit the current effort to slow resistance development because AuNC@CPP abolished the emergence of drug-resistant strains induced by antibiotics.

  View details for DOI 10.1039/d2nr01003h

  View details for PubMedID 35796201

• Minimally invasive trans-tympanic eustachian tube occlusion animal model. International journal of pediatric otorhinolaryngology Kouhi, A., Xia, A., Khomtchouk, K., Santa Maria, P. L. 2022; 156: 111070

  Abstract

  OBJECTIVE: Eustachian tube dysfunction is believed to be involved in the pathogenesis of many middle ear diseases including chronic suppurative otitis media. We aimed to describe a simple and reliable animal model of Eustachian Tube obstruction to further research into middle ear disorders.STUDY DESIGN: Prospective cohort study in animals.SETTING: University laboratory.SUBJECTS AND METHODS: 30 mice C57Bl/6J (n=15) and CBA/CaJ (n=15) aged 6-8 weeks received transtympanic Eustachian tube occlusion on left ear trough an acute tympanic membrane perforation using thermoplastic latex used in dental procedures (gutta percha). Control mice (n=6) received tympanic membrane perforation only. At two and four weeks, the mice were observed for signs of Eustachian tube dysfunction and compared to control ears. ET dysfunction was defined as presence of effusion in the middle ear.RESULTS: 100% (n=30) of the treated ears had otoscopic signs of Eustachian tube dysfunction at two weeks and the endpoint time of four weeks, compared to 0% in control mice (0/6). Temporary head tilt lasting up to 2 days were observed in 3 mice (10%). No other potential adverse events were recorded. No bacterial growth was determined in the middle ear fluid.CONCLUSION: We describe a technically easy and reliable method for Eustachian tube occlusion in mice with an excellent success rate and minimal morbidity.

  View details for DOI 10.1016/j.ijporl.2022.111070

  View details for PubMedID 35228098

• New Medical Device and Therapeutic Approvals in Otolaryngology: State of the Art Review 2020. OTO open Brenner, M. J., Shenson, J. A., Rose, A. S., Valdez, T. A., Takashima, M., Ahmed, O. G., Weissbrod, P. A., Hong, R. S., Djalilian, H., Wolf, J. S., Morrison, R. J., Santa Maria, P. L., Erbele, I. D. 2021; 5 (4): 2473974X211057035

  Abstract

  Objectives: To evaluate new drugs and devices relevant to otolaryngology-head and neck surgery that were approved by the US Food and Drug Administration (FDA) in 2020.Data Sources: Publicly available device and therapeutic approvals from ENT (ear, nose, and throat), anesthesia, neurology (neurosurgery), and plastic and general surgery FDA committees.Review Methods: Members of the American Academy of Otolaryngology-Head and Neck Surgery's Medical Devices and Drugs Committee reviewed new therapeutics and medical devices from a query of the FDA's device and therapeutic approvals. Two independent reviewers assessed the drug's or device's relevance to otolaryngology, classified to subspecialty field, with a critical review of available scientific literature.Conclusions: The Medical Devices and Drugs Committee reviewed 53 new therapeutics and 1094 devices (89 ENT, 140 anesthesia, 511 plastic and general surgery, and 354 neurology) approved in 2020. Ten drugs and 17 devices were considered relevant to the otolaryngology community. Rhinology saw significant improvements around image guidance systems; indications for cochlear implantation expanded; several new monoclonal therapeutics were added to head and neck oncology's armamentarium; and several new approvals appeared for facial plastics surgery, pediatric otolaryngology, and comprehensive otolaryngology.Implications for Practice: New technologies and pharmaceuticals offer the promise of improving how we care for otolaryngology patients. However, judicious introduction of innovations into practice requires a nuanced understanding of safety, advantages, and limitations. Working knowledge of new drugs and medical devices approved for the market helps clinicians tailor patient care accordingly.

  View details for DOI 10.1177/2473974X211057035

  View details for PubMedID 34790883

• Topical Therapy Failure in Chronic Suppurative Otitis Media is Due to Persister Cells in Biofilms. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Santa Maria, P. L., Kaufman, A. C., Bacacao, B., Thai, A., Chen, X., Xia, A., Cao, Z., Fouad, A., Bekale, L. A. 2021

  Abstract

  OBJECTIVE: Chronic suppurative otitis media (CSOM) is characterized by a chronically draining middle ear. CSOM is typically treated with multiple courses of antibiotics or antiseptics which are successful in achieving quiescence; however, the disease is prone to relapse. Understanding why these treatment failures occur is essential.STUDY DESIGN: The minimum inhibitory concentration (MIC), minimal biofilm eradication concentration, and the inhibitory zone were determined for ototopicals and ofloxacin for the laboratory strains and CSOM-derived isolates. The percentage of persister cells and bacterial biofilm formation were measured. Disease eradication was tested in a validated in-vivo model of CSOM after treatment with ofloxacin.SETTING: Microbiology Laboratory.METHODS: Basic science experiments were performed to measure the effectiveness of a number of compounds against CSOM bacteria in a number of distinct settings.RESULTS: The minimal biofilm eradication concentration is higher than is physiologically achievable with commercial preparations, except for povo-iodine. Clincial isolates of CSOM have equivalent biofilm-forming ability but increased proportions of persister cells. Ofloxacin can convert to inactive disease temporarily but fails to eradicate disease in an in-vivo model.CONCLUSIONS: Higher percentages of persister cells in clinical CSOM isolates are associated with resistance to ototopicals. Current ototopicals, except povo-iodine, have limited clinical effectiveness; however, it is unknown what the maximum achievable concentration is and there are ototoxicity concerns. Fluoroquinolones, while successful in producing inactive disease in the short term, have the potential to encourage antimicrobial resistance and disease recalcitrance and do not achieve a permanent remission. Given these limitations, clinicians should consider surgery earlier or use of clinically safe concentrations of povo-iodine earlier into the treatment algorithm.

  View details for DOI 10.1097/MAO.0000000000003222

  View details for PubMedID 34149028

• Middle Cranial Fossa Approach to Repair Tegmen Dehiscence Using Self-setting Calcium Phosphate Cement: A Retrospective Case Review. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Bulsara, V. M., Kim, G. S., Fouad, A. M., Bulsara, M. K., Santa Maria, P. L. 2021

  Abstract

  OBJECTIVES: To review the outcomes of repairing tegmen dehiscence using the middle cranial fossa approach with a self-setting bone cement.STUDY DESIGN: Retrospective case series.SETTING: Two academic tertiary hospitals.PATIENTS: All patients presenting for surgical repair of tegmen dehiscence and with postoperative follow-up for at least 6 months between October 2015 and July 2019.INTERVENTION: Surgical repair using a middle cranial fossa approach using a layered reconstruction with temporalis fascia and self-setting calcium phosphate bone cement.MAIN OUTCOME MEASURES: Perioperative complications, recurrence of presenting symptoms/disease, hearing, and facial nerve grade.RESULTS: The cohort consisted of 22 patients with 23 tegmen dehiscence repairs (1 sequential bilateral repair). There were 16 males and 6 females with an average age at operation of 52.6 years. Repairs were left sided in 9, right sided in 12 patients, and bilateral in 1 patient. No patients had recurrence of presenting symptoms or disease at most recent follow-up. Preoperative hearing was maintained in all patients. Two patients (9% of repairs) experienced delayed partial temporary facial nerve weakness House-Brackman grade 2 and 4 which had recovered by 8 weeks postoperative.CONCLUSION: We demonstrate a technique for repairing tegmen dehiscence of the middle cranial fossa floor that has excellent postoperative outcomes. We highlight potential technical challenges in this approach as well as the need for counseling for potential partial transient facial nerve dysfunction.

  View details for DOI 10.1097/MAO.0000000000003110

  View details for PubMedID 33710151

• Antimicrobial Gold Nanoclusters Eradicate Escherichia coli Biofilms and Are Nontoxic by Oral Administration. ACS applied bio materials Cao, Z., Chen, J., Tran, J., Chen, X., Bacacao, B., Bekale, L. A., Santa Maria, P. L. 2020; 3 (8): 5275-5286

  Abstract

  Escherichia coli biofilms are a major causative agent of many intestinal infections, and there is ongoing research aimed at E. coli biofilm eradication. Gold nanoclusters (AuNCs) conjugated with various surface ligands have been extensively investigated for antimicrobial properties and provide a potential solution. There is little known about their in vivo safety because current standards of nanosafety research involve incubation of AuNCs with cells in vitro to confirm biocompatibility. In addition to systemic administration, nanosafety research on AuNC-based antimicrobials designed to treat gastrointestinal infections must also consider the potential for inducing gastrointestinal disorders. We report the design and application of two AuNCs coated with either hydroxyl (AuNC@PEG-OH)- or amine (AuNC@PEG-NH2)-functionalized poly(ethylene glycol), which enables the eradication of E. coli biofilms. Gastrointestinal safety of AuNC@PEG-OH and AuNC@PEG-NH2 was evaluated in healthy mice up to 35 days after administration by oral gavage at a dose of 10 mg/kg (or 1 mg/mL) daily for 14 days. No changes were detected in the histopathology of major organs, serum chemistry, hematology, and feces. Thus, oral administration of AuNCs is unlikely to be of concern for systemic toxicity or in the induction of gastrointestinal illnesses. Further studies on increasing time exposure and doses are necessary to determine whether toxicity occurs at higher doses or whether there is no adverse effect limit.

  View details for DOI 10.1021/acsabm.0c00641

  View details for PubMedID 35021702

• Long-Term Hearing Outcomes Following Stereotactic Radiosurgery in Vestibular Schwannoma Patients-A Retrospective Cohort Study Santa Maria, P. L., Shi, Y., Gurgel, R. K., Corrales, C., Soltys, S. G., Santa Maria, C., Murray, K., Chang, S. D., Blevins, N. H., Gibbs, I. C., Jackler, R. K. OXFORD UNIV PRESS INC. 2019: 550–59

  View details for DOI 10.1093/neuros/nyy407

  View details for Web of Science ID 000491255600014

• Single Administration of a Sustained-Release Formulation of KB-R7785 Inhibits Tympanic Membrane Regeneration in an Animal Model JOURNAL OF INTERNATIONAL ADVANCED OTOLOGY Maria, P. L., Maria, C. S., Kim, S., Yang, Y. P. 2016; 12 (3): 237-240

  Abstract

  A pressure equalization tube placed within the tympanic membrane is the only clinically available method for inhibiting tympanic membrane regeneration. Problems associated with this include associated otorrhea, biofilm formation, medial migration of the tube, tube retention, induction of granulation tissue, and a small but significant rate of cholesteatoma. We aimed to demonstrate that a single administration of a sustained-release polymer formulation of KB-R7785 maintains tympanic membrane perforation for at least 6 months.Sustained-release KB-R7785 was delivered within a novel polymer hydrogel to 20 mice with bilateral acute tympanic membrane perforations (a total of 40 perforations). The perforations were monitored at 3-month intervals until 9 months.At 3 months, 90% of perforations were open (n=36/40). At 6 months, 75% of perforations were open (total n=30/40). At 9 months, 22.5% of perforations were open (total n=6/40). The majority of tympanic membrane perforations (75%) were open (not healed) beyond 6 months and close (fully healed) prior to 9 months (77.5%). Once healed, tympanic membranes resembled their normal histological appearance.This study demonstrates that a single administration of a sustained-release polymer formulation of KB-R7785 inhibits tympanic membrane regeneration for 6-9 months.

  View details for DOI 10.5152/iao.2016.3124

  View details for PubMedID 28031154

• Heparin Binding Epidermal Growth Factor-Like Growth Factor Heals Chronic Tympanic Membrane Perforations With Advantage Over Fibroblast Growth Factor 2 and Epidermal Growth Factor in an Animal Model OTOLOGY & NEUROTOLOGY Maria, P. L., Weierich, K., Kim, S., Yang, Y. P. 2015; 36 (7): 1279-1283

  Abstract

  That heparin binding epidermal growth factor-like growth factor (HB-EGF) heals chronic tympanic membrane (TM) perforations at higher rates than fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) in an animal model.A nonsurgical treatment for chronic TM perforation would benefit those unable to access surgery or those unable to have surgery, as well as reducing the cost of tympanoplasty. Growth factor (GF) treatments have been reported in the literature with variable success with the lack of a suitable animal providing a major obstacle.The GFs were tested in a validated mouse model of chronic TM perforation. A bioabsorbable hydrogel polymer was used to deliver the GF at a steady concentration as it dissolved over 4 weeks. A control (polymer only, n = 18) was compared to polymer loaded with HB-EGF (5 μg/ml, n = 18), FGF2 (100 μg/ml, n = 19), and EGF (250 μg/ml, n = 19). Perforations were inspected at 4 weeks.The healing rates, as defined as 100% perforation closure, were control (5/18, 27.8%), HB-EGF (15/18, 83.3%), FGF2 (6/19, 31.6%), and EGF (3/19, 15.8%). There were no differences between FGF2 (p = 0.80) and EGF (p = 0.31) with control healing rates. HB-EGF (p = 0.000001) showed a significant difference for healing. The HB-EGF healed TMs showed layers similar to a normal TM, whereas the other groups showed a lack of epithelial migration.This study confirms the advantage of HB-EGF over two other commonly used growth factors and is a promising nonsurgical treatment of chronic TM perforations.

  View details for DOI 10.1097/MAO.0000000000000795

  View details for Web of Science ID 000358409500021

• Heparin Binding Epidermal Growth Factor-Like Growth Factor Heals Chronic Tympanic Membrane Perforations With Advantage Over Fibroblast Growth Factor 2 and Epidermal Growth Factor in an Animal Model. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Santa Maria, P. L., Weierich, K., Kim, S., Yang, Y. P. 2015; 36 (7): 1279-83

  Abstract

  That heparin binding epidermal growth factor-like growth factor (HB-EGF) heals chronic tympanic membrane (TM) perforations at higher rates than fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF) in an animal model.A nonsurgical treatment for chronic TM perforation would benefit those unable to access surgery or those unable to have surgery, as well as reducing the cost of tympanoplasty. Growth factor (GF) treatments have been reported in the literature with variable success with the lack of a suitable animal providing a major obstacle.The GFs were tested in a validated mouse model of chronic TM perforation. A bioabsorbable hydrogel polymer was used to deliver the GF at a steady concentration as it dissolved over 4 weeks. A control (polymer only, n = 18) was compared to polymer loaded with HB-EGF (5 μg/ml, n = 18), FGF2 (100 μg/ml, n = 19), and EGF (250 μg/ml, n = 19). Perforations were inspected at 4 weeks.The healing rates, as defined as 100% perforation closure, were control (5/18, 27.8%), HB-EGF (15/18, 83.3%), FGF2 (6/19, 31.6%), and EGF (3/19, 15.8%). There were no differences between FGF2 (p = 0.80) and EGF (p = 0.31) with control healing rates. HB-EGF (p = 0.000001) showed a significant difference for healing. The HB-EGF healed TMs showed layers similar to a normal TM, whereas the other groups showed a lack of epithelial migration.This study confirms the advantage of HB-EGF over two other commonly used growth factors and is a promising nonsurgical treatment of chronic TM perforations.

  View details for DOI 10.1097/MAO.0000000000000795

  View details for PubMedID 26075672

• A new theory on the pathogenesis of acquired cholesteatoma: Mucosal traction. Laryngoscope Jackler, R. K., Santa Maria, P. L., Varsak, Y. K., Nguyen, A., Blevins, N. H. 2015; 125: S1-S14

  Abstract

  Although the migration of its squamous outer surface of the tympanic membrane has been well characterized, there is a paucity of data available concerning the migratory behavior of its medial mucosal surface. Existing theories of primary acquired cholesteatoma pathogenesis do not adequately explain the observed characteristics of the disease. We propose a new hypothesis, based upon a conjecture that mucosal membrane interactions are the driving force in cholesteatoma.A retrospective chart review and a prospective observational cohort study in rats.After developing the new theory, it was tested through both clinical and experimental observations. To evaluate whether impairment of middle ear mucociliary migration would influence cholesteatoma formation, a retrospective chart review evaluating cholesteatoma occurrence in a sizable population of patients with either primary ciliary dyskinesia (PCD) or cystic fibrosis (CF) was performed. To study mucosal migration on the medial aspect of the tympanic membrane, ink tattoos were monitored over time in a rat model.No cholesteatomas were identified in either PCD patients (470) or in CF patients (1,910). In the rat model, mucosa of the posterior pars tensa migrated toward the posterior superior quadrant, whereas the mucosa of the anterior pars tensa migrated radially toward the annulus.Mucosal coupling with traction generated by interaction of migrating opposing surfaces provides the first comprehensive theory that explains the observed characteristics of primary acquired cholesteatoma. The somewhat counterintuitive hypothesis that cholesteatoma is fundamentally a mucosal disease has numerous therapeutic implications.4. Laryngoscope, 125:S1-S14, 2015.

  View details for DOI 10.1002/lary.25261

  View details for PubMedID 26013635

• Heparin Binding-Epidermal Growth Factor-Like Growth Factor for the Regeneration of Chronic Tympanic Membrane Perforations in Mice TISSUE ENGINEERING PART A Maria, P. L., Kim, S., Varsak, Y. K., Yang, Y. P. 2015; 21 (9-10): 1483-1494

  Abstract

  We aim to explore the role of epidermal growth factor (EGF) ligand shedding in tympanic membrane wound healing and to investigate the translation of its modulation in tissue engineering of chronic tympanic membrane perforations. Chronic suppurative otitis media (CSOM) is an infected chronic tympanic membrane perforation. Up to 200 million suffer from its associated hearing loss and it is the most common cause of pediatric hearing loss in developing countries. There is a need for nonsurgical treatment due to a worldwide lack of resources. In this study, we show that EGF ligand shedding is essential for tympanic membrane healing as it's inhibition, with KB-R7785, leads to chronic perforation in 87.9% (n=58) compared with 0% (n=20) of controls. We then show that heparin binding-EGF-like growth factor (5 μg/mL), which acts to shed EGF ligands, can regenerate chronic perforations in mouse models with 92% (22 of 24) compared with 38% (10 of 26), also with eustachian tube occlusion with 94% (18 of 19) compared with 9% (2 of 23) and with CSOM 100% (16 of 16) compared with 41% (7 of 17). We also show the nonototoxicity of this treatment and its hydrogel delivery vehicle. This provides preliminary data for a clinical trial where it could be delivered by nonspecialist trained healthcare workers and fulfill the clinical need for a nonsurgical treatment for chronic tympanic membrane perforation and CSOM.

  View details for DOI 10.1089/ten.tea.2014.0474

  View details for Web of Science ID 000353952300002

  View details for PubMedID 25567607

  View details for PubMedCentralID PMC4426296

• Hearing Preservation Surgery for Cochlear Implantation: A Meta-analysis OTOLOGY & NEUROTOLOGY Maria, P. L., Gluth, M. B., Yuan, Y., Atlas, M. D., Blevins, N. H. 2014; 35 (10): E256-E269

  Abstract

  To examine the results of hearing preservation in cochlear implantation surgery to identify surgical technical factors, electrode array design factors, and steroid usage, which predicts greater low-frequency hearing preservation.A thorough search of Medline and Pubmed of English studies from January 1, 1995, to January 1, 2013, was performed using the key words "electric and acoustic hearing" or "hybrid cochlear implant" or "EAS cochlear implant" or "partial deafness cochlear implant" or "bimodal hearing cochlear implant" or "hearing preservation cochlear implant."The meta-analysis was conducted according to the PRISMA statement. Only articles in English were included. Studies were included if hearing preservation was the primary end point. A final number of 24 studies met the inclusion criteria.Patient populations were analyzed as intention to treat. Data were extracted from raw audiograms where possible. Data were excluded if not all explanatory variables were present or if variable values were ambiguous.The weighted least-squares regression method was used to determine the predictive power of each explanatory variable across all studies.In this meta-analysis, the following are associated with better hearing preservation: cochleostomy over the round window approach, posterior tympanotomy over the suprameatal approach, a slow electrode array insertion technique over insertion of less than 30 seconds, a soft tissue cochleostomy seal over a fibrin glue only seal and the use of postoperative systemic steroids. Longer electrode arrays, topical steroid use, and lubricant use for electrode array insertion did not give an advantage.

  View details for Web of Science ID 000345157200001

• Hearing preservation surgery for cochlear implantation: a meta-analysis. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Santa Maria, P. L., Gluth, M. B., Yuan, Y., Atlas, M. D., Blevins, N. H. 2014; 35 (10): e256-69

  Abstract

  To examine the results of hearing preservation in cochlear implantation surgery to identify surgical technical factors, electrode array design factors, and steroid usage, which predicts greater low-frequency hearing preservation.A thorough search of Medline and Pubmed of English studies from January 1, 1995, to January 1, 2013, was performed using the key words "electric and acoustic hearing" or "hybrid cochlear implant" or "EAS cochlear implant" or "partial deafness cochlear implant" or "bimodal hearing cochlear implant" or "hearing preservation cochlear implant."The meta-analysis was conducted according to the PRISMA statement. Only articles in English were included. Studies were included if hearing preservation was the primary end point. A final number of 24 studies met the inclusion criteria.Patient populations were analyzed as intention to treat. Data were extracted from raw audiograms where possible. Data were excluded if not all explanatory variables were present or if variable values were ambiguous.The weighted least-squares regression method was used to determine the predictive power of each explanatory variable across all studies.In this meta-analysis, the following are associated with better hearing preservation: cochleostomy over the round window approach, posterior tympanotomy over the suprameatal approach, a slow electrode array insertion technique over insertion of less than 30 seconds, a soft tissue cochleostomy seal over a fibrin glue only seal and the use of postoperative systemic steroids. Longer electrode arrays, topical steroid use, and lubricant use for electrode array insertion did not give an advantage.

  View details for DOI 10.1097/MAO.0000000000000561

  View details for PubMedID 25233333

• Sigmoid sinus dehiscence resurfacing as treatment for pulsatile tinnitus. The Journal of laryngology and otology Santa Maria, P. L. 2013: 1-3

  Abstract

  Aim: To report a case of sigmoid sinus dehiscence presenting with pulsatile tinnitus and treated successfully with resurfacing. Case report: This patient presented with pulsatile tinnitus due to sigmoid sinus dehiscence. This was successfully treated using only soft tissue resurfacing. Conclusion: Sigmoid sinus dehiscence is a rare but treatable cause of pulsatile tinnitus. It can occur in the absence of a diverticulum, and is not necessarily limited to the transverse sigmoid junction. When resurfacing, care must be taken not to significantly alter the extraluminal diameter of the sigmoid in a dominant sinus, as this raises the risk of post-operative hydrocephalus.

  View details for DOI 10.1017/S0022215113000649

  View details for PubMedID 23595093

• Hearing Preservation Surgery for Cochlear Implantation-Hearing and Quality of Life After 2 Years OTOLOGY & NEUROTOLOGY Maria, P. L., Domville-Lewis, C., Sucher, C. M., Chester-Browne, R., Atlas, M. D. 2013; 34 (3): 526-531

  Abstract

  To study the benefits of hearing preservation surgery in cochlear implantation after 2 years.A retrospective cohort study.Performed at a single academic institution between 2008 and 2010Thirteen patients (1 bilateral): 43% male and 57% female subjects. Mean age at surgery was 51 years (range, 32-72 yr). Average duration of deafness was 25 years (range, 5-62 yr).Hearing preservation cochlear implantation surgery performed with the Med-El FlexEAS electrode.Pure tone thresholds, speech perception in quiet and noise and quality of life (Abbreviated Profile of Hearing Aid Benefit [APHAB] and Glasgow Hearing Aid Benefit [GHABP Scales] up to and including 2 years after surgery.At the first postoperative audiogram, the hearing preservation rate was 100% (complete (42.9%), partial (50%), and minimal (7.1%)). After 24 months, the breakdown was complete (25%), partial (12.5%), minimal (37.5%) and complete loss (12.5%). There was a trend in improvement in all areas of APHAB) with significant improvements in the background noise and reverberation categories as well as the global scores. The GHABP scores showed high levels of use, benefit, and low levels of residual disease.Hearing preservation can be achieved in the short term but deteriorates with time over the medium term at a rate greater than that can be expected with the natural progression of the disease. Patients show benefits in speech outcomes and quality of life regardless of whether hearing preservation was achieved in the medium term.

  View details for DOI 10.1097/MAO.0b013e318281e0c9

  View details for Web of Science ID 000316452300030

  View details for PubMedID 23503094

• Tympanic Membrane Wound Healing in Rats Assessed by Transcriptome Profiling LARYNGOSCOPE Santa Maria, P. L., Redmond, S. L., McInnes, R. L., Atlas, M. D., Ghassemifar, R. 2011; 121 (10): 2199-2213

  Abstract

  The aim of this study is to elucidate transcriptional changes that occur in response to tympanic membrane (TM) perforation in rats and to infer key genes and molecular events in the healing process.A prospective cohort study of 393 male Sprague-Dawley (Rattus norvegicus) rats.Sprague-Dawley rats were randomly allocated into either control or perforation groups spanning a 7-day time period. Perforation groups consisted of 12-hour, 24-hour, 36-hour, 2-day, 3-day, 4-day, 5-day, six-day, and 7-day time points. The left TMs of all perforation groups were perforated and the RNA extracted at the specified time point postperforation. Subsequent analysis was performed using Agilent's 4 × 44 k whole rat genome arrays (40 in total) to assess wound-healing gene expression over a 7-day time period.Over a 7-day time course and at nine time points that encompassed the wounding and progression of healing, a total of 3,262 genes were differentially expressed. In this study the transcripts most upregulated occurred at 12 hours. These were Stefin A2 (344-fold), Stefin 2 (143-fold), and Natriuretic peptide precursor type B (222-fold). Those most downregulated also occurred at 12 hours. These were alcohol dehydrogenase 7 (13.1-fold) and gamma-butyrobetaine hydroxylase (10.4-fold). Results were validated by quantitative real-time polymerase chain reaction.The findings of this study provide a baseline against which to identify disease-related molecular signatures, biomarkers, and to develop new treatments for TM conditions based on molecular evidence.

  View details for DOI 10.1002/lary.22150

  View details for Web of Science ID 000295228800029

  View details for PubMedID 21919009

• Tumor Control Following Stereotactic Radiosurgery in Patients with Vestibular Schwannomas - A Retrospective Cohort Study. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Santa Maria, P. L., Shi, Y., Aaron, K. A., Gurgel, R. K., Corrales, C. E., Soltys, S. G., Santa Maria, C., Chang, S. D., Blevins, N. H., Jackler, R. K., Gibbs, I. C. 2021

  Abstract

  BACKGROUND: To better counsel vestibular schwannoma patients, it is necessary to understand the tumor control rates of stereotactic radiosurgery (SRS).OBJECTIVES: To determine tumor control rates, factors determining control and complication rates following SRS.METHODS: Tertiary hospital retrospective cohort.RESULTS: 579 tumors (576 patients) were treated with SRS. 477 tumors (474 patients, 82%) had ≥1 year follow up and 60% (344) ≥3 years follow up. 88% of tumors had primary SRS and 6.7% salvage SRS. Median follow up time was 4.6 years. At 3 years, the tumor control rate of primary SRS was 89% (258 of 290) in sporadic tumors compared to 43% in Neurofibromatosis type II (3 of 17) (p < 0.01). Our bivariable survival data analysis showed that Neurofibromatosis type II, documented pre-SRS growth, tumor measured by maximum dimension, SRS given as nonprimary treatment increased hazard of failure to control. There was one case of malignancy and another of rapid change following intra-tumoral hemorrhage. For tumors undergoing surgical salvage (25 of 59), 56% had a total or near-total resection, 16% had postoperative CSF leak, with 12% new facial paralysis (House-Brackmann grade VI) and worsening of facial nerve outcomes (House-Brackmann grade worse in 59% at 12 mo).CONCLUSIONS: Control of vestibular schwannoma after primary SRS occurs in the large majority. Salvage surgical treatment was notable for higher rates of postoperative complications compared to primary surgery reported in the literature.

  View details for DOI 10.1097/MAO.0000000000003285

  View details for PubMedID 34353978

• Stereotactic Radiosurgery for Vestibular Schwannoma Outcomes in Patients With Perfect Word Recognition-A Retrospective Cohort Study. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Fouad, A. n., Tran, E. D., Feng, A. Y., Alyono, J. C., Ma, Y. n., Blevins, N. H., Jackler, R. K., Santa Maria, P. L. 2021

  Abstract

  To investigate tumor control rate and hearing outcomes following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) cases with perfect (100%) word recognition score (WRS).A retrospective cohort study.Tertiary referral center.Inclusion criteria were receiving primary SRS, a pretreatment WRS of 100%, and availability of both pre- and posttreatment audiometric data for evaluation.SRS delivered by Cyberknife.Tumor growth rates and audiological outcomes after SRS.The cohort consisted of 139 patients, with more than 1-year follow-up (mean 6.1 yrs). SRS tumor control rate was 87% for the whole cohort. Growth before SRS was documented in 24% (n = 34 of 139). The proportion of sporadic VS cases who maintained hearing (decline <10 dB of pure-tone audiometry or <20% of WRS) at 3 years was 50%, at 5 years was 45%, and at 10 years was 42%. In multivariate analysis, increased age was found to be predictive of increased hearing loss (p = 0.03), while the following factors were shown not to be significant: sex (p = 0.5), tumor size (p = 0.2), pre-SRS tumor growth (p = 0.5), and target volume (p = 0.42).Among patients with VS who had perfect WRS and underwent SRS, the overall tumor control rate was 87% comparable to observation. Hearing maintenance and preservation of "serviceable" hearing rates after 5 years in VS patients with perfect WRS treated by SRS is less than that when comparing to similar observation cohorts. Given this finding we do not advocate using SRS to preserve hearing, over observation, in tumors with perfect WRS.

  View details for DOI 10.1097/MAO.0000000000003039

  View details for PubMedID 33443977

• Long-Term Health Utilization and Outcomes in Chronic Suppurative Otitis Media. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Thai, A., Aaron, K. A., Kaufman, A. C., Santa Maria, P. L. 2021: 1945998211050626

  Abstract

  To report health utilization patterns and outcomes of medical and surgical management in patients with chronic suppurative otitis media (CSOM).Retrospective cohort.Academic otology clinic.This study included 175 patients with CSOM with a first clinic visit at our institution between March 2011 and November 2016. All patients displayed a diagnosis of CSOM by International Classification of Diseases code, had at least 1 episode of active CSOM (defined as perforation with otorrhea), and had a documented history of chronic ear infections. The mean age was 49.5 ± 1.5 years, 53% were female, and mean follow-up time was 3.5 ± 0.3 years.Patients had an average of 9.5 ± 0.5 otology visits, 4.7 ± 0.4 prescriptions, and 1.7 ± 0.1 surgeries, with estimated per patient cost ranging from $3927 to $20,776. Under medical management, 69% of patients displayed recurrence of disease, with a median time to recurrence of 4 months. For tympanoplasty and tympanomastoidectomy, median time to recurrence was similar at 5 and 7 years, respectively (P = .73). At the most recent visit, the prevalence of all patients with CSOM displaying moderate or worse sensorineural hearing loss (SNHL) was 41%.CSOM represents a major public health issue with high health care utilization and associated costs. Surgery is superior to medical therapy for achieving short- to medium-term inactive disease. Patients with CSOM display a high SNHL burden.

  View details for DOI 10.1177/01945998211050626

  View details for PubMedID 34637356

• Locally administered heparin-binding epidermal growth factor-like growth factor reduces radiation-induced oral mucositis in mice. Scientific reports Chen, J., Bekale, L. A., Khomtchouk, K. M., Xia, A., Cao, Z., Ning, S., Knox, S. J., Santa Maria, P. L. 2020; 10 (1): 17327

  Abstract

  Oral mucositis refers to lesions of the oral mucosa observed in patients with cancer being treated with radiation with or without chemotherapy, and can significantly affect quality of life. There is a large unmet medical need to prevent oral mucositis that can occur with radiation either alone or in combination with chemotherapy. We investigated the efficacy of locally administered heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent epithelial proliferation and migration stimulator of the oral mucosa as a potential therapy to prevent radiation induced oral mucositis. Using a single dose (20Gy) of radiation to the oral cavity of female C57BL/6J mice, we evaluated the efficacy of HB-EGF treatment (5l of 10g/ml) solution. The results show that HB-EGF delivered post radiation, significantly increased the area of epithelial thickness on the tongue (dorsal tongue (42,106 vs 53,493 m2, p<0.01), ventral tongue (30,793 vs 39,095 m2, *p<0.05)) compared to vehicle control, enhanced new epithelial cell division, and increased the quality and quantity of desmosomes in the oral mucosa measured in the tongue and buccal mucosa. This data provides the proof of concept that local administration of HB-EGF has the potential to be developed as a topical treatment to mitigate oral mucositis following radiation.

  View details for DOI 10.1038/s41598-020-73875-7

  View details for PubMedID 33060741

• Antimicrobial Gold Nanoclusters Eradicate Escherichia coli Biofilms and Are Nontoxic by Oral Administration ACS APPLIED BIO MATERIALS Cao, Z., Chen, J., Tran, J., Chen, X., Bacacao, B., Bekale, L. A., Santa Maria, P. L. 2020; 3 (8): 5275–86

  View details for DOI 10.1021/acsabm.0c00641

  View details for Web of Science ID 000604598800054

• A Review of the Contribution of Mast Cells in Wound Healing: Involved Molecular and Cellular Mechanisms CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY Komi, D., Khomtchouk, K., Maria, P. 2020; 58 (3): 298–312

  View details for DOI 10.1007/s12016-019-08729-w

  View details for Web of Science ID 000534884400002

• A design-thinking approach to therapeutic translation: tympanic regeneration. Current opinion in otolaryngology & head and neck surgery Santa Maria, P. L. 2020

  Abstract

  Clinician researchers face the pressures of meeting academic benchmarks combined with advancing new therapies to patients. The vast majority of drug discoveries fail in translation. A new method of meeting the challenges of preclinical therapeutic translation is presented using the example of tympanic regeneration.The key to a design-thinking approach to therapeutic translation is to 'begin with the end in mind' by widening the scope of the problem, with multiple points of view, to not only understand the disease but the context for the patient and the health system in which it occurs. Idea for therapeutics should be tested in relevant models early and once proof of efficacy is established, translational milestones that represent the greatest risk, such as safety and toxicity should be addressed first. It is important to seek the feedback of industry early to understand what milestones should be best addressed next with limited academic resources. Whenever proceeding, guidelines for maintaining scientific reproducibility should be followed to minimize risk of failure during transfer into industry.A Design-thinking approach addresses the potential failures in drug discovery and preclinical translation.

  View details for DOI 10.1097/MOO.0000000000000650

  View details for PubMedID 32833885

• New Medical Device and Therapeutic Approvals in Otolaryngology: State of the Art Review of 2019. OTO open Rameau, A. n., Hong, R. S., Djalilian, H. n., Erbele, I. D., Phillips, K. M., Capasso, R. n., Rose, A. S., Brenner, M. J., Santa Maria, P. L. 2020; 4 (2): 2473974X20932506

  Abstract

  To review new devices and drugs relevant to otolaryngology-head and neck surgery that were approved by the US Food and Drug Administration (FDA) in 2019.Approval notifications for 2019 were extracted from the ENT (ear, nose, and throat) and general and plastic surgery sections of the FDA's medical devices and therapeutics listings.New therapeutics and medical devices identified from the query were analyzed by members of the American Academy of Otolaryngology-Head and Neck Surgery's Medical Devices and Drugs Committee. Technologies were assessed by 2 independent reviewers to ascertain relevance to otolaryngology, prioritized, and classified to subspecialty field with critical review based on extant scientific literature.Query of the FDA drug and device database returned 105 ENT devices (50 cleared, 55 with premarket approval, and 0 de novo), 543 general and plastic surgery devices (372 cleared, 170 with premarket approval, and 1 de novo), and 46 new otolaryngology-relevant drug approvals that occurred in 2019. Advances spanned all subspecialty areas with otology predominating, primarily due to hearing-related technologies. While scientific evidence was available for all new devices, there was significant heterogeneity in rigor of supporting scientific data.Technological and pharmaceutical innovation is an important catalyst for advances in the surgical specialties. Familiarity with new devices and therapeutics in otolaryngology-head and neck surgery ensures that clinicians keep abreast of developments with potential to improve prevailing standards of care.

  View details for DOI 10.1177/2473974X20932506

  View details for PubMedID 32537556

  View details for PubMedCentralID PMC7268138

• A novel mouse model of chronic suppurative otitis media and its use in preclinical antibiotic evaluation. Science advances Khomtchouk, K. M., Kouhi, A. n., Xia, A. n., Bekale, L. A., Massa, S. M., Sweere, J. M., Pletzer, D. n., Hancock, R. E., Bollyky, P. L., Santa Maria, P. L. 2020; 6 (33): eabc1828

  Abstract

  Chronic suppurative otitis media (CSOM) is a neglected pediatric disease affecting 330 million worldwide for which no new drugs have been introduced for over a decade. We developed a mouse model with utility in preclinical drug evaluation and antimicrobial discovery. Our model used immune-competent mice, tympanic membrane perforation and inoculation with luminescent Pseudomonas aeruginosa that enabled bacterial abundance tracking in real-time for 100 days. The resulting chronic infection exhibited hallmark features of clinical CSOM, including inhibition of tympanic membrane healing and purulent ear discharge. We evaluated the standard care fluoroquinolone ofloxacin and demonstrated that this therapy resulted in a temporary reduction of bacterial burden. These data are consistent with the clinical problem of persistent infection in CSOM and the need for therapeutic outcome measures that assess eradication post-therapeutic endpoint. We conclude that this novel mouse model of CSOM has value in investigating new potential therapies.

  View details for DOI 10.1126/sciadv.abc1828

  View details for PubMedID 32851190

  View details for PubMedCentralID PMC7428333

• Long-term quality of life in patients with vestibular schwannoma managed with microsurgery. The Journal of laryngology and otology Santa Maria, C., Santa Maria, P. L., Bulsara, V., Jayawardena, J., Caldow, J. D., Png, L. H., Atlas, M. D. 2019: 1-7

  Abstract

  Little is known about the long term (greater than 10 years) quality of life in patients with vestibular schwannoma. This study aimed to evaluate long-term outcomes in patients with vestibular schwannoma.A retrospective cohort study was performed across 2 academic institutions, with patients followed at least 10 years after vestibular schwannoma surgery (2000 to 2007). Telephone interviews were used to assess quality of life using the Glasgow Benefit Inventory and short form 12 item (version 2) health survey.A total of 99 out of 110 patients were included. Increasing age and symptom burden were associated with poorer quality of life (p = 0.01 and 0.02, respectively). The presence of imbalance, headache and facial nerve dysfunction were all associated with poorer quality of life scores (p = 0.01, 0.04 and 0.02, respectively).Identifying and managing post-operative symptoms may improve quality of life in vestibular schwannoma patients and can guide clinical decision making.

  View details for DOI 10.1017/S0022215119002172

  View details for PubMedID 31668161

• Quantitative assessment of bacterial growth phase utilizing flow cytometry. Journal of microbiological methods Khomtchouk, K. M., Weglarz, M., Bekale, L. A., Kolesnik, I., Bollyky, P. L., Santa Maria, P. L. 2019: 105760

  Abstract

  Flow cytometry is currently underutilized for bacterial phenotyping and standard microbiological techniques do not provide phenotypic information about the state of the bacterial disease. Pseudomonas aeruginosa is a human pathogen of increased importance in public health due to both the ability to cause chronic diseases and the prevalence of functionally different subsets that can be difficult to treat and diagnose. In the present study, we used flow cytometry to analyze the growth phase of P. aeruginosa. A simple method for single cell quantitative detection of bacterial biofilm and planktonic cells was established with a combination of membrane permeable (SYTO 60) and impermeable (TOTO-1) dyes plus the addition of polystyrene counting beads. The specificity of the dye combination for biofilm detection was determined by comparison with impaired biofilm forming strains of P. aeruginosa LasI/RhlI-/- and ∆PfPhage. Results suggest that flow cytometric bacterial phenotyping serves as an expandable platform that may be useful for enumeration of population level variation in P. aeruginosa studies.

  View details for DOI 10.1016/j.mimet.2019.105760

  View details for PubMedID 31678132

• A Review of the Contribution of Mast Cells in Wound Healing: Involved Molecular and Cellular Mechanisms. Clinical reviews in allergy & immunology Komi, D. E., Khomtchouk, K., Santa Maria, P. L. 2019

  Abstract

  Mast cells (MCs), apart from their classic role in allergy, contribute to a number of biologic processes including wound healing. In particular, two aspects of their histologic distribution within the skin have attracted the attention of researchers to study their wound healing role; they represent up to 8% of the total number of cells within the dermis and their cutaneous versions are localized adjacent to the epidermis and the subdermal vasculature and nerves. At the onset of a cutaneous injury, the accumulation of MCs and release of proinflammatory and immunomodulatory mediators have been well documented. The role of MC-derived mediators has been investigated through the stages of wound healing including inflammation, proliferation, and remodeling. They contribute to hemostasis and clot formation by enhancing the expression of factor XIIIa in dermal dendrocytes through release of TNF-alpha, and contribute to clot stabilization. Keratinocytes, by secreting stem cell factor (SCF), recruit MCs to the site. MCs in return release inflammatory mediators, including predominantly histamine, VEGF, interleukin (IL)-6, and IL-8, that contribute to increase of endothelial permeability and vasodilation, and facilitate migration of inflammatory cells, mainly monocytes and neutrophils to the site of injury. MCs are capable of activating the fibroblasts and keratinocytes, the predominant cells involved in wound healing. MCs stimulate fibroblast proliferation during the proliferative phase via IL-4, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) to produce a new extracellular matrix (ECM). MC-derived mediators including fibroblast growth factor-2, VEGF, platelet-derived growth factor (PDGF), TGF-beta, nerve growth factor (NGF), IL-4, and IL-8 contribute to neoangiogenesis, fibrinogenesis, or reepithelialization during the repair process. MC activation inhibition and targeting the MC-derived mediators are potential therapeutic strategies to improve wound healing through reduced inflammatory responses and scar formation.

  View details for PubMedID 30729428

• Sensorineural Hearing Loss in the Nonimplanted Ear Following Cochlear Implantation in a Patient With Bilateral Enlarged Vestibular Aqueducts. Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology Vaisbuch, Y. n., Thai, A. n., Pirko, S. L., Santa Maria, P. L. 2019

  Abstract

  To document the case of a patient with bilateral enlarged vestibular aqueducts who experienced sensorineural hearing loss in the nonimplanted ear following unilateral cochlear implantation complicated by perilymph gusher requiring lumbar drain insertion and to highlight the need to counsel regarding the risk of potential hearing loss to the contralateral ear when preparing for cochlear implants in the setting of inner ear malformations.One patient with bilateral enlarged vestibular aqueducts in a tertiary referral center.Cochlear implantation complicated by perilymph gusher requiring lumbar drain insertion.Bone conduction hearing thresholds, word recognition scores.The patient underwent unilateral cochlear implantation, which was complicated by a perilymphatic gusher and necessitated placement of an intraoperative lumbar drain. On postoperative day 1, the patient reported hearing loss in the opposite ear. The word recognition score in the contralateral ear dropped from 24% at preimplantation to 8% at 2-weeks postimplantation, and did not improve at 6 months postimplantation. Moreover, the bone conduction threshold at 1 kHz worsened from 20 dB preoperatively to no response at 75 dB (the limit of the testing equipment) at 2-weeks postoperatively and only partially improved to 40 dB at 6 months postimplantation.As patients with inner ear malformations potentially have direct high-pressure anatomical connections between the perilymphatic spaces and the cerebrospinal fluid, they are at risk of hearing loss in the nonimplanted ear during cochlear implantation. This case highlights the need for potential additional patient counseling regarding this risk in the nonimplanted ear.

  View details for DOI 10.1097/MAO.0000000000002319

  View details for PubMedID 31348130

• Predicting sequential bilateral cochlear implantation performance in postlingually deafened adults; A retrospective cohort study CLINICAL OTOLARYNGOLOGY Smulders, Y. E., Hendriks, T., Stegeman, I., Eikelboom, R. H., Sucher, C., Upson, G., Browne, R., Jayakody, D., Santa Maria, P. L., Atlas, M. D., Friedland, P. L. 2018; 43 (6): 1500–1507

  Abstract

  To identify which preoperative patient characteristics influence sequential bilateral cochlear implantation performance and to create a statistical model that predicts benefit.Multicentre retrospective cohort study.All patients were operated in four academic teaching hospitals in Perth, Australia, and followed up by audiologists of the Ear Science Institute Australia.A total of 92 postlingually deafened adult patients who had undergone sequential cochlear implantations between 19 June 1990 and 14 March 2016 were included. Patients were excluded if the 12-month follow-up consonant-nucleus-consonant (CNC) phoneme score was missing.The effect of 18 preoperative factors on the CNC phoneme score in quiet (at 65 dB SPL) with the second cochlear implant (CI2) one year after implantation.Two factors were positively correlated to speech understanding with CI2: Wearing a hearing aid (HA) before receiving CI2 (r = 0.46, P = 0.00) and the maximum CNC phoneme score with the first CI (CI1) (r = 0.21, P = 0.05). Two factors were negatively correlated: the length of hearing loss before CI2 in the second implanted ear (r = -0.25, P = 0.02) and preoperative pure tone average (PTA) (0.5, 1, 2 kHz) before CI2 in the second implanted ear (r = -0.27, P = 0.01). The following model could be created: predicted CNC phoneme score with CI2 (%) = 16 + (44 * HA use before CI2 (yes)) - (0.22 * length of hearing loss before CI2 (years)) + (0.23 * CNC phoneme score with CI1 (%)). Because the effect of HA use before implantation played such a major role, we also created a model after exclusion of the HA factor: Predicted CNC phoneme score with CI2 (%) = 82 - (0.17 * length of hearing loss before CI2 (years)) - (0.27 * PTA in second implanted ear before CI2 (0.5, 1, 2 kHz)) + (0.20 * CNC phoneme score with CI1 (%)).Advanced age or a long interval between implantations does not necessarily lead to poor CI2 results. Patients who are successful HA users before CI2, who have a low PTA before CI2, a high CNC phoneme score with CI1 and a limited length of hearing loss before CI2, are likely to be successful CI2 recipients.

  View details for PubMedID 30022607

• Long-Term Hearing Outcomes Following Stereotactic Radiosurgery in Vestibular Schwannoma Patients-A Retrospective Cohort Study. Neurosurgery Santa Maria, P. L., Shi, Y., Gurgel, R. K., Corrales, C. E., Soltys, S. G., Santa Maria, C., Murray, K., Chang, S. D., Blevins, N. H., Gibbs, I. C., Jackler, R. K. 2018

  Abstract

  BACKGROUND: An understanding of the hearing outcomes is needed for treatment counseling for patients with vestibular schwannomas (VS).OBJECTIVE: To determine long-term hearing results following stereotactic radiosurgery (SRS) for VS and identify any influential variables.METHODS: Tertiary hospital retrospective cohort.RESULTS: There were 579 tumors (576 patients) treated with SRS. Eighty-two percent (473) of tumors had ≥1 yr and 59% (344 ≥3 yr follow-up. In the 244 tumor ears, with measurable hearing before SRS who were followed ≥1 yr, 14% (31) had improved hearing, 13% (29) unchanged hearing, and 74% (158) had worsened hearing. In 175 patients with ≥3 yr follow-up and who had measurable hearing pretreatment, 6% (11 ears) improved hearing, 31% (54 ears) unchanged hearing, and 63% (110 ears) had worsened hearing. Patients with tumors with larger target volumes (P=0.040) and with neurofibromatosis type 2 (NF2; P=0.017) were associated with poorer hearing (P=0.040). Patients with word recognition scores (WRS) of 50% or poorer had tumors with a larger volume (P=0.0002), larger linear size (P=0.032), and NF2 (P=0.045). Traditionally reported hearing outcomes using the Gardner Robertson maintenance of PTA ≤50 db or WRS ≥50% were 48% at 3 yr, which overestimates hearing outcomes compared to the above reporting standards.CONCLUSION: Hearing declines over time in VS treated with SRS in a high proportion of cases. The frequency and magnitude of long-term hearing decline following SRS argues against prophylactic radiation for small tumors in hearing ears with undetermined growth behavior.

  View details for PubMedID 30247723

• Optical Coherence Tomography of the Tympanic Membrane and Middle Ear: A Review Tan, H., Maria, P., Wijesinghe, P., Kennedy, B., Allardyce, B., Eikelboom, R., Atlas, M., Dilley, R. SAGE PUBLICATIONS LTD. 2018: 424–38

  Abstract

  Objective To evaluate the recent developments in optical coherence tomography (OCT) for tympanic membrane (TM) and middle ear (ME) imaging and to identify what further development is required for the technology to be integrated into common clinical use. Data Sources PubMed, Embase, Google Scholar, Scopus, and Web of Science. Review Methods A comprehensive literature search was performed for English language articles published from January 1966 to January 2018 with the keywords "tympanic membrane or middle ear,"optical coherence tomography," and "imaging." Conclusion Conventional imaging techniques cannot adequately resolve the microscale features of TM and ME, sometimes necessitating diagnostic exploratory surgery in challenging otologic pathology. As a high-resolution noninvasive imaging technique, OCT offers promise as a diagnostic aid for otologic conditions, such as otitis media, cholesteatoma, and conductive hearing loss. Using OCT vibrometry to image the nanoscale vibrations of the TM and ME as they conduct acoustic waves may detect the location of ossicular chain dysfunction and differentiate between stapes fixation and incus-stapes discontinuity. The capacity of OCT to image depth and thickness at high resolution allows 3-dimensional volumetric reconstruction of the ME and has potential use for reconstructive tympanoplasty planning and the follow-up of ossicular prostheses. Implications for Practice To achieve common clinical use beyond these initial discoveries, future in vivo imaging devices must feature low-cost probe or endoscopic designs and faster imaging speeds and demonstrate superior diagnostic utility to computed tomography and magnetic resonance imaging. While such technology has been available for OCT, its translation requires focused development through a close collaboration between engineers and clinicians.

  View details for PubMedID 29787354

• Age-Related Hearing Loss: Innovations in Hearing Augmentation. Otolaryngologic clinics of North America Vaisbuch, Y., Santa Maria, P. L. 2018

  Abstract

  Age-related hearing loss is a multifactorial condition that affects more than one-third of the aging population. Left untreated it can increase the risk of cognitive decline, dementia, social isolation, depression, and falls. Hearing augmentation devices exhibit improved digital sound processing and Smartphone connectivity. Stigma remains one of the prominent barriers and todays devices offer in the canal models, miniature sizes, and camouflage with the hair or skin color. Although rigorous scientific efforts are made in the research field of inner ear regeneration and some clinical early phase studies do exist, to date, the clinical availability is still some time away.

  View details for PubMedID 29735277

• In reference to Evidence against the mucosal traction theory in cholesteatoma. The Laryngoscope Jackler, R. K., Santa Maria, P. L., Blevins, N. H. 2018

  View details for PubMedID 29392724

• Biomedical device innovation methodology: applications in biophotonics JOURNAL OF BIOMEDICAL OPTICS Beswick, D. M., Kaushik, A., Beinart, D., McGarry, S., Yew, M., Kennedy, B. F., Maria, P. 2018; 23 (2)

  View details for DOI 10.1117/1.JBO.23.2.021102

  View details for Web of Science ID 000425275200006

• Epithelial separation theory for post-tonsillectomy secondary hemorrhage: evidence in a mouse model and potential heparin-binding epidermal growth factor-like growth factor therapy EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY Beswick, D. M., Santa Maria, C., Ayoub, N. F., Capasso, R., Santa Maria, P. 2018; 275 (2): 569–78

  Abstract

  To provide histological evidence to investigate a theory for post-tonsillectomy secondary hemorrhage (PTH) in a mouse model and to evaluate the potential for heparin-binding epidermal growth factor-like growth factor (HB-EGF) treatment on wound healing in this model.A prospective randomized single-blinded cohort study. A uniform tongue wound was created in 84 mice (day 0). Mice were randomized to HB-EGF (treatment, n = 42) or saline (control, n = 42). In treatment mice, HB-EGF 5 µg/ml was administered intramuscularly into the wound daily (days 0-14). In control mice, normal saline was administered daily. Three mice from each group were sacrificed daily through day 14 and the wounds evaluated histologically by blinded reviewers.Key stages of wound healing, including keratinocyte proliferation and migration, wound contraction, epithelial separation, and neoangiogenesis, are defined with implications for post-tonsillectomy wound healing. Epithelial separation (59 vs. 100%, p = 0.003) and wound reopening (8 vs. 48%, p < 0.001) were reduced with HB-EGF. Epithelial thickness (220 vs. 30 µm, p = 0.04) was greater with HB-EGF. Wound closure (days 4-5 vs. day 6, p = 0.01) occurred earlier with HB-EGF.In healing of oral keratinocytes on muscle epithelial separation secondary to muscle, contraction occurs concurrently with neoangiogenesis in the base of the wound, increasing the risk of hemorrhage. This potentially explains why post-tonsillectomy secondary hemorrhage occurs and its timing. HB-EGF-treated wounds showed greater epithelial thickness, less frequent epithelial separation and wound reopening, and earlier wound closure prior to neovascularization, suggesting that HB-EGF may be a potential preventative therapy for PTH.NA-animal studies or basic research.

  View details for PubMedID 29188436

• A novel thermal compression device for perioperative warming: a randomized trial for feasibility and efficacy BMC ANESTHESIOLOGY Maria, P., Maria, C., Eisenried, A., Velasquez, N., Kannard, B., Ramani, A., Kahn, D., Wheeler, A., Brock-Utne, J. 2017; 17: 102

  Abstract

  Inadvertent perioperative hypothermia (IPH) leads to surgical complications and increases length of stay. IPH rates are high with the current standard of care, forced air warming (FAW). Our hypothesis is that a prototype thermal compression device that heats the popliteal fossa and soles of the feet, with lower leg compression, increases perioperative temperatures and reduces IPH compared to the current standard of care.Thirty six female breast surgery patients, at a tertiary academic hospital, were randomized to the device or intraoperative FAW (stage I) with a further 18 patients randomized to the device with a single heating area only (stage II, popliteal fossa or sole of the feet). Stage I: 37 patients recruited (final 36). Stage II: 18 patients recruited (final 18).general anesthesia with esophageal monitoring for over 30 min, legs available and able to fit the device and no contraindications to leg heating or compression. The intervention was: Stage I: Investigational prototype thermal compression device (full device group) or intraoperative FAW. Stage II: Device with only a single heating location. Primary outcomes were perioperative temperatures and incidence of IPH. Secondary outcomes were local skin temperature, general and thermal comfort scores and presence of perioperative complications, including blood loss.Mean temperatures in the full device group were significantly higher than the FAW group in the pre-operative (36.7 vs 36.4 °C, p < 0.001), early intraoperative (36.3 vs 35.9 °C, p < 0.001), intraoperative (36.6 vs 36.2 °C, p < 0.001) and postoperative periods (36.8 vs 36.5 °C, p < 0.001). The incidence of IPH in the device group was also significantly lower (16.7% vs 72.0%, p = 0.001). Thermal comfort scores were significantly higher in the full device group and hypothermia associated wound complications were higher in the FAW group.The thermal compression device is feasible and has efficacy over the FAW. Further studies are recommended to investigate clinically significant outcomes.clinicaltrials.gov ( NCT02155400 ).

  View details for PubMedID 28800725

• Functional Outcomes of Heparin-Binding Epidermal Growth Factor-Like Growth Factor for Regeneration of Chronic Tympanic Membrane Perforations in Mice TISSUE ENGINEERING PART A Maria, P. L., Gottlieb, P., Maria, C. S., Kim, S., Puria, S., Yang, Y. P. 2017; 23 (9-10): 436-444

  Abstract

  We aim to demonstrate that regeneration of chronic tympanic perforations with heparin-binding epidermal growth factor-like growth factor (HB-EGF) delivered by an injectable hydrogel restored hearing to levels similar to that of nonperforated tympanic membranes. Chronic tympanic membrane perforation is currently managed as an outpatient surgery with tympanoplasty. Due to the costs of this procedure in the developed world and a lack of accessibility and resources in developing countries, there is a great need for a new treatment that does not require surgery. In this study, we show in a mouse model through measurement of auditory brainstem response and distortion product otoacoustic emissions that tympanic perforations lead to hearing loss and this can be predominantly recovered with HB-EGF treatment (5 μg/mL). Our animal model suggests a return to function between 2 and 6 months after treatment. Auditory brainstem response thresholds had returned to the control levels at 2 months, but the distortion product otoacoustic emissions returned between 2 and 6 months. We also show how the vibration characteristics of the regenerated tympanic membrane, as measured by laser Doppler vibrometry, can be similar to that of an unperforated tympanic membrane. Using the best available methods for preclinical evaluation in animal models, it is likely that HB-EGF-like growth factor treatment leads to regeneration of chronic tympanic membrane perforations and restoration of the tympanic membrane to normal function, suggesting a potential route for nonsurgical treatment.

  View details for DOI 10.1089/ten.tea.2016.0395

  View details for Web of Science ID 000401342400007

• Functional Outcomes of Heparin Binding - Epidermal Growth Factor Like Growth Factor for Regeneration of Chronic Tympanic Membrane Perforations in Mice. Tissue engineering. Part A Santa Maria, P. L., Gotlieb, P., Santa Maria, C., Puria, S., Kim, S., Yang, Y. P. 2017

  Abstract

  We aim to demonstrate that regeneration of chronic tympanic perforations with heparin-binding epidermal growth factor-like growth factor (HB-EGF) delivered by an injectable hydrogel restored hearing to levels similar to that of nonperforated tympanic membranes. Chronic tympanic membrane perforation is currently managed as an outpatient surgery with tympanoplasty. Due to the costs of this procedure in the developed world and a lack of accessibility and resources in developing countries, there is a great need for a new treatment that does not require surgery. In this study, we show in a mouse model through measurement of auditory brainstem response and distortion product otoacoustic emissions that tympanic perforations lead to hearing loss and this can be predominantly recovered with HB-EGF treatment (5 μg/mL). Our animal model suggests a return to function between 2 and 6 months after treatment. Auditory brainstem response thresholds had returned to the control levels at 2 months, but the distortion product otoacoustic emissions returned between 2 and 6 months. We also show how the vibration characteristics of the regenerated tympanic membrane, as measured by laser Doppler vibrometry, can be similar to that of an unperforated tympanic membrane. Using the best available methods for preclinical evaluation in animal models, it is likely that HB-EGF-like growth factor treatment leads to regeneration of chronic tympanic membrane perforations and restoration of the tympanic membrane to normal function, suggesting a potential route for nonsurgical treatment.

  View details for DOI 10.1089/ten.TEA.2016.0395

  View details for PubMedID 28142401

• Predicting Sequential Cochlear Implantation Performance: A Systematic Review AUDIOLOGY AND NEURO-OTOLOGY Smulders, Y., Hendriks, T., Eikelboom, R., Stegeman, I., Santa Maria, P., Atlas, M., Friedland, P. 2017; 22 (6): 356–63

  Abstract

  This systematic review of the literature reveals which pre-operative factors affect sequential cochlear implantation outcomes in adults. The findings can help health care prof-essionals provide evidence-based advice on the expected benefits from a second cochlear implant (CI). We searched PubMed, EMBASE, and the Cochrane database from November 1977 to August 26, 2017, using the terms "sequential cochlear implantation"; the most frequently cited predictors for unilateral cochlear implantation performance and other potential predictors for sequential implantation outcome; and "speech perception," "localization" as well as synonyms of all of the above. Ten studies were included. The effects of age, duration of hearing loss, time between implantations, preoperative hearing, etiology of hearing loss, hearing aid use and duration of follow-up on sequential cochlear implantation performance were studied. The literature has shown that duration of deafness, age at onset of deafness, etiology of hearing loss, and preoperative speech perception score are (inversely) related to unilateral cochlear implantation outcome in adults. One would expect that these factors would also affect sequential bilateral implantation outcome. However, the best available evidence to date shows that advanced age, a long duration of deafness, or a long interval between implantations should not be considered negative factors when considering sequential bilateral cochlear implantation.

  View details for PubMedID 29719297

• No systemic exposure of transtympanic heparin-binding epidermal growth factor like growth factor. Drug and chemical toxicology Santa Maria, P. L., Kim, S., Yang, Y. P. 2016; 39 (4): 451-454

  Abstract

  Heparin-binding epidermal growth factor like growth factor (HB-EGF) is an emerging therapeutic for the regeneration of the tympanic membrane (TM).Our aim was to determine whether the doses of HB-EGF delivered in a sustained release hydrogel into a middle ear mouse model, would be measurable in the systemic circulation. We also aimed to observe, in the scenario that the intended dose was absorbed directly into the circulation, whether these levels could be measured above the background levels of HB-EGF in the circulation.A total of 12 mice had transtympanic injections of 5 μg/ml of HB-EGF contained within a previously described novel hydrogel vehicle, while another 12 mice had intravenous delivery of 10 μg/kg of HB-EGF. Intravenous blood samples were collected at 0-, 3-, 24-, 168-, 288- and 720-h post-injection. A double-antibody sandwich one-step process enzyme-linked immunosorbent assay (ELISA) was used to determine the level of HB-EGF in the serum.No mice in the transtympanic administration group and no mice in the intravenous administration group were found to have blood level measured above that in the controls.The inability of the positive control to measure levels above background, suggest the total dose used in our studies, even if 100% absorbed into the system circulation is insignificant.HB-EGF at the doses and delivery method proposed for treatment of chronic TM perforation in a mouse model are likely to have no measurable systemic effect.

  View details for DOI 10.3109/01480545.2016.1143482

  View details for PubMedID 26887920

• Type I Tympanoplasty Meta-Analysis: A Single Variable Analysis OTOLOGY & NEUROTOLOGY Tan, H. E., Maria, P. L., Eikelboom, R. H., Anandacoomaraswamy, K. S., Atlas, M. D. 2016; 37 (7): 838-846

  Abstract

  To determine which independent variables influence the efficacy of type I tympanoplasty in adult and pediatric populations.A search of the PubMed database and Cochrane Database of Systematic Reviews using the key words "tympanoplasty OR myringoplasty" from January 1966 to July 2014 was performed.Studies reporting outcomes of myringoplasty or Type I tympanoplasty in primary non-cholesteatomatous chronic tympanic membrane (TM) perforation were included.Of 4,698 abstracts reviewed, 214 studies involving 26,097 patients met our inclusion criteria and contributed to meta-analysis.The primary outcome of success was defined as closure rate at 12 months. The independent variables analyzed were age, follow-up period, approach, graft material, perforation cause, size, location, ear dryness, and surgical technique. Only those studies providing data on a given parameter of interest could be included when comparing each variable.The weighted average success rate of tympanic closure was 86.6%. Based on this meta-analysis, pediatric surgery has a 5.8% higher failure rate than adults and there is no correlation between follow-up period and success. Other variables associated with improved closure rates include perforation with a size less than 50% of total area (improved by 6.1%) and the use of cartilage as a graft (improved by 2.8% compared with fascia), while ears that were operated on while still discharging, those in different locations of the pars tensa, or using different surgical approaches or techniques did not have significantly different outcomes.

  View details for DOI 10.1097/MAO.0000000000001099

  View details for Web of Science ID 000380621200019

  View details for PubMedID 27273405

• Ossicular calisthenics: Pneumomassage of the tympanic membrane LARYNGOSCOPE Mudry, A., Maria, P. S., Jackler, R. K. 2016; 126 (5): 1180-1186

  Abstract

  Throughout the latter portion of the 19th and early 20th centuries, pneumomassage devices were widely used by otologists to treat a variety of ear diseases. The so-called eardrum massagers produced a regular, repetitive, oscillatory movement through modifying the air pressure in the ear canal. The goal of this study was to trace the invention, clinical use, technological diversification, abandonment, and ultimate resurrection of tympanic pneumomassage.Review of the 19th- and early 20th-century medical journals, texts, and trade catalogs concerning the tympanic pneumomassage.In 1884, the Belgian otologist Charles Delstanche introduced what he called a rarefacteur, and 5 years later he introduced the masseur du tympan. This lead to a frenzied development of imaginative mechanical and electrical pneumassagers with a goal to exercise the tympanic membrane and ossicles to overcome contraction and rigidity. Tympanic pneumomassage rose to prominence in mainstream otology as a treatment for otitis media, chronic deafness, and tinnitus. After gradually fading out of the otological practice by the 1930s, pneumomassage was reintroduced in the 1980s after a half century of obscurity, this time as a novel invention notably for the treatment of Menière's disease.The golden era of pneumomassage illustrates the ingenuity of otologists and medical instrument makers in creating a proliferation of clever devices, as well as how highly touted treatment methods may become widely adopted by practitioners despite the lack of efficacy. It also noteworthy that historic therapeutic methods are sometimes reintroduced for purposes not envisioned by their original makers.N/A. Laryngoscope, 2015.

  View details for DOI 10.1002/lary.25556

  View details for Web of Science ID 000374769400036

  View details for PubMedID 26421977

• Iatrogenic Phenol Injury Causing Facial Paralysis With Tympanic Membrane and Ossicular Necrosis OTOLOGY & NEUROTOLOGY Maria, P. L., Corrales, C. E., Sevy, A. B., Jackler, R. K. 2016; 37 (4): 385-387

  Abstract

  To describe a serious iatrogenic injury and propose means of reducing the risk of its reoccurrence.A 21-year-old man who suffered facial paralysis, complete necrosis of the tympanic membrane, and ossicular discontinuity because of chemical burn from accidental application of copious amounts of topical anesthetic phenol into the ear.Conservative management of facial paralysis and delayed reconstruction of the tympanic membrane and ossicular chain.Gradual recovery to grade 1/6 facial function, successful repair of the tympanic membrane, but persistent 30-dB conductive hearing loss after partial ossicular replacement prosthesis presumably because of scarring.Phenol is a highly toxic chemical, topically to both skin and eyes. Absorbed through the skin it can have lethal cardiotoxicity. It is also potent neurotoxin at concentrations much lower (4-7%) than used for tympanic membrane anesthesia (89%) and has long been used therapeutically to destroy nerves in patients of contractions or intractable pain. Otologists need to have a healthy respect for the dangers of using phenol. As only a minute quantity is needed for tympanic anesthesia, commercially available prepackaged applicators are preferred. Storage of stock bottles of 89% phenol solutions in clinical settings risks injury to both patients and practitioners.

  View details for DOI 10.1097/MAO.0000000000000979

  View details for Web of Science ID 000374881000016

  View details for PubMedID 26927759

• In Response to the Letter to the Editor Regarding: Heparin Binding-Epidermal Growth Factor-Like Growth Factor for the Regeneration of Chronic Tympanic Membrane Perforations in Mice. Tissue engineering. Part A Santa Maria, P. L., Kim, S., Varsak, Y. K., Yang, Y. P. 2016; 22 (5-6): 570-571

  View details for DOI 10.1089/ten.TEA.2016.0059

  View details for PubMedID 26908042

• Mouse model of experimental Eustachian tube occlusion: a surgical technique ACTA OTO-LARYNGOLOGICA Varsak, Y. K., Maria, P. L. 2016; 136 (1): 12-17

  Abstract

  The present study demonstrates a mouse model of chronic Eustachian tube (ET) dysfunction using a surgical technique that is reproducible and effective with low mortality and morbidity.To create a reproducible and effective mouse model of ET obstruction with a low operative morbidity.Forty healthy, male CBA/CaJ mice underwent the procedure. ET obstruction was performed on one side under general anesthesia; A small piece of dental material (Gutta Percha Points, Meta Biomed, Chungbuk, Korea) was placed via the tympanic orifice of the ET to occlude the entire ET. The contralateral ears of animals served as a control. One month after the operation, all ears were inspected under an operating microscope for signs of ET dysfunction. Primary outcome measures were the signs of ET dysfunction inspected through tympanic membrane (TM) 4 weeks after the operation and confirmation of ET occlusion by post-mortem dissection.Forty (100%) of the treated mice ears developed ET dysfunction, as confirmed by the middle ear appearance on otoscopy and dissection post-mortem and 0% of the control ears at 4 weeks. The most common otoscopic signs were thickened TMs and middle ear effusions. No mortality or morbidity occurred either from anesthesia or surgery.

  View details for DOI 10.3109/00016489.2015.1082191

  View details for Web of Science ID 000365678800003

  View details for PubMedID 26381832

• In reference to A new theory on the pathogenesis of acquired cholesteatoma: Mucosal traction. Laryngoscope Jackler, R. K., Santa Maria, P. L., Varsak, Y. K., Blevins, N. H., Nguyen, A. 2016; 126 (1): E50-?

  View details for DOI 10.1002/lary.25542

  View details for PubMedID 26267761

• Psychophysical Map Stability in Bilateral Sequential Cochlear Implantation: Comparing Current Audiology Methods to a New Statistical Definition EAR AND HEARING Domville-Lewis, C., Santa Maria, P. L., Upson, G., Chester-Browne, R., Atlas, M. D. 2015; 36 (5): 497-504

  Abstract

  The purpose of this study was to establish a statistical definition for stability in cochlear implant maps. Once defined, this study aimed to compare the duration taken to achieve a stable map in first and second implants in patients who underwent sequential bilateral cochlear implantation. This article also sought to evaluate a number of factors that potentially affect map stability.A retrospective cohort study of 33 patients with sensorineural hearing loss who received sequential bilateral cochlear implantation (Cochlear, Sydney, Australia), performed by the senior author. Psychophysical parameters of hearing threshold scores, comfort scores, and the dynamic range were measured for the apical, medial, and basal portions of the cochlear implant electrode at a range of intervals postimplantation. Stability was defined statistically as a less than 10% difference in threshold, comfort, and dynamic range scores over three consecutive mapping sessions. A senior cochlear implant audiologist, blinded to implant order and the statistical results, separately analyzed these psychophysical map parameters using current assessment methods. First and second implants were compared for duration to achieve stability, age, gender, the duration of deafness, etiology of deafness, time between the insertion of the first and second implant, and the presence or absence of preoperative hearing aids were evaluated and its relationship to stability. Statistical analysis included performing a two-tailed Student's t tests and least squares regression analysis, with a statistical significance set at p ≤ 0.05.There was a significant positive correlation between the devised statistical definition and the current audiology methods for assessing stability, with a Pearson correlation coefficient r = 0.36 and a least squares regression slope (b) of 0.41, df(58), 95% confidence interval 0.07 to 0.55 (p = 0.004). The average duration from device switch on to stability in the first implant was 87 days using current audiology methods and 81 days using the statistical definition, with no statistically significant difference between assessment methods (p = 0.2). The duration to achieve stability in the second implant was 51 days using current audiology methods and 60 days using the statistical method, and again no difference between the two assessment methods (p = 0.13). There was a significant reduction in the time to achieve stability in second implants for both audiology and statistical methods (p < 0.001 and p = 0.02, respectively). There was a difference in duration to achieve stability based on electrode array region, with basal portions taking longer to stabilize than apical in the first implant (p = 0.02) and both apical and medial segments in second implants (p = 0.004 and p = 0.01, respectively). No factors that were evaluated in this study, including gender, age, etiology of deafness, duration of deafness, time between implant insertion, and the preoperative hearing aid status, were correlated with stability duration in either stability assessment method.Our statistical definition can accurately predict cochlear implant map stability when compared with current audiology practices. Cochlear implants that are implanted second tend to stabilize sooner than the first, which has a significant impact on counseling before a second implant. No factors evaluated affected the duration required to achieve stability in this study.

  View details for DOI 10.1097/AUD.0000000000000154

  View details for Web of Science ID 000360630900001

  View details for PubMedID 25710778

• A new theory on the pathogenesis of acquired cholesteatoma: Mucosal traction LARYNGOSCOPE Jackler, R. K., Maria, P. L., Varsak, Y. K., Anh Nguyen, A., Blevins, N. H. 2015; 125: S1-S14

  Abstract

  Although the migration of its squamous outer surface of the tympanic membrane has been well characterized, there is a paucity of data available concerning the migratory behavior of its medial mucosal surface. Existing theories of primary acquired cholesteatoma pathogenesis do not adequately explain the observed characteristics of the disease. We propose a new hypothesis, based upon a conjecture that mucosal membrane interactions are the driving force in cholesteatoma.A retrospective chart review and a prospective observational cohort study in rats.After developing the new theory, it was tested through both clinical and experimental observations. To evaluate whether impairment of middle ear mucociliary migration would influence cholesteatoma formation, a retrospective chart review evaluating cholesteatoma occurrence in a sizable population of patients with either primary ciliary dyskinesia (PCD) or cystic fibrosis (CF) was performed. To study mucosal migration on the medial aspect of the tympanic membrane, ink tattoos were monitored over time in a rat model.No cholesteatomas were identified in either PCD patients (470) or in CF patients (1,910). In the rat model, mucosa of the posterior pars tensa migrated toward the posterior superior quadrant, whereas the mucosa of the anterior pars tensa migrated radially toward the annulus.Mucosal coupling with traction generated by interaction of migrating opposing surfaces provides the first comprehensive theory that explains the observed characteristics of primary acquired cholesteatoma. The somewhat counterintuitive hypothesis that cholesteatoma is fundamentally a mucosal disease has numerous therapeutic implications.4. Laryngoscope, 125:S1-S14, 2015.

  View details for DOI 10.1002/lary.25261

  View details for Web of Science ID 000358374200001

• A case of stereotactic radiation in skull base solitary fibrous tumor: more harm than good? Journal of neurological surgery reports Santa Maria, P. L., Abuzeid, W. M., Nayak, J. V., Chang, S. D., Blevins, N. H. 2014; 75 (2): e214-6

  Abstract

  Objective Due to its location, total resection of a skull base solitary fibrous tumor (SFT) can lead to morbidity with injury to lower cranial nerves, and a decision must be made between subtotal resection with possible stereotactic radiotherapy or total resection with cranial nerve morbidity. We report the long-term outcomes and review the literature of a case of stereotactic radiation in SFT to provide evidence for making this decision. Design A retrospective case review. Setting An academic tertiary referral center. Results We present a case with > 10 years follow-up of radiation following skull base SFT, initially misdiagnosed as schwannoma, where radiotherapy did not improve recurrence or metastatic behavior and led to complications during subsequent surgical resection. Conclusions SFT often masquerades as schwannoma, especially in the skull base. Careful immunohistochemistry, including CD34 expression, is critical to the diagnosis and management. This case highlights that total tumor resection of SFT remains the gold standard of treatment. Stereotactic radiation is not recommended in the management of skull base SFT.

  View details for DOI 10.1055/s-0034-1387196

  View details for PubMedID 25485216

  View details for PubMedCentralID PMC4242816

• When is the best timing for the second implant in pediatric bilateral cochlear implantation? Laryngoscope Santa Maria, P. L., Oghalai, J. S. 2014; 124 (7): 1511-1512

  View details for DOI 10.1002/lary.24465

  View details for PubMedID 24122858

• Is office-based myringoplasty a suitable alternative to surgical tympanoplasty? Laryngoscope Santa Maria, P. L., Oghalai, J. S. 2014; 124 (5): 1053-1054

  View details for DOI 10.1002/lary.24221

  View details for PubMedID 24114573

• In Response to: Regeneration of Chronic Tympanic Membrane Perforation Using an EGF-Releasing Chitosan Patch. Tissue engineering. Part A Santa Maria, P. L. 2013; 19 (19-20): 2109-2110

  View details for DOI 10.1089/ten.TEA.2013.0351

  View details for PubMedID 23859315

• In Response to: Regeneration of Chronic Tympanic Membrane Perforation Using an EGF-Releasing Chitosan Patch. Tissue engineering. Part A Santa Maria, P. L. 2013; 19 (19-20): 2109-2110

  View details for DOI 10.1089/ten.TEA.2013.0351

  View details for PubMedID 23859315

• Unique microbiology of chronically unstable canal wall down tympanomastoid cavities: considerations for surgical revision. journal of laryngology and otology Gluth, M. B., Tan, B. Y., Santa Maria, P. L., Atlas, M. D. 2013; 127 (5): 458-462

  Abstract

  Objective: To review the microbiology of open tympanomastoid cavities in patients who underwent revision surgery due to chronic instability. Methods: This paper describes a retrospective chart review of surgical revision cases of chronically unstable open mastoid cavities. Patient records from 2000 to 2010 were reviewed for the type of organism cultured, antimicrobial resistance and the presence of cholesteatoma. Results: In total, 121 revision surgical procedures were performed on 101 patients. Seventy-nine procedures involved culture specimen processing, 37 of which were positive. The most commonly cultured organism was Staphylococcus aureus, which was more than twice as common as any other pathogen. The presence of cholesteatoma had no impact on the likelihood of a positive culture or polymicrobial culture. Antimicrobial-resistant pathogens were uncommon. Conclusion: A positive culture was not an overwhelmingly common characteristic of unstable tympanomastoid cavities. Furthermore, antimicrobial resistance did not appear to play an essential role in leading patients towards revision open mastoid surgery.

  View details for DOI 10.1017/S0022215113000583

  View details for PubMedID 23552343

• Pott's puffy tumour and intracranial complications of frontal sinusitis in pregnancy JOURNAL OF LARYNGOLOGY AND OTOLOGY Domville-Lewis, C., Friedland, P. L., Maria, P. L. 2013; 127: S35-S38

  Abstract

  A Pott's puffy tumour is a subperiosteal abscess and osteomyelitis of the frontal bone secondary to frontal sinusitis. Intracranial complications are seen in approximately 40 per cent of cases and are potentially life-threatening; such complications have not previously been reported in pregnancy.A 21-year-old woman at 35 weeks' gestation presented with a history of frontal headaches and swelling, periorbital oedema, pain and chemosis. Imaging confirmed Pott's puffy tumour with right-sided epidural empyema and periorbital cellulitis. A multidisciplinary team was involved in the patient's management. Intravenous antibiotics were commenced and initial percutaneous drainage through the frontal sinus skin was performed, followed by endoscopic sinus drainage. A caesarean section was performed 3 days later. Complete resolution of the sinus and intracranial collections was noted on imaging performed six weeks later.This case highlights the challenges of managing rare intracranial complications of sinusitis in pregnancy, and the importance of multidisciplinary care.

  View details for DOI 10.1017/S0022215112001673

  View details for Web of Science ID 000312461900008

  View details for PubMedID 22892137

• Keratinocyte growth factor 1, fibroblast growth factor 2 and 10 in the healing tympanic membrane following perforation in rats. Journal of molecular histology Santa Maria, P. L., Redmond, S. L., Atlas, M. D., Ghassemifar, R. 2011; 42 (1): 47-58

  Abstract

  The aim of this study was to provide a transcriptome profile of Keratinocyte Growth Factor (KGF)-1, Fibroblast Growth Factor (FGF) 2 and FGF10 (KGF2) in the healing rat tympanic membrane (TM) over 7 days and an immunohistochemical account over 14 days following perforation. KGF1, FGF2, and FGF10 play important roles in TM wound healing. The tympanic membranes of rats were perforated and sacrificed at time points over a 14-day period following perforation. The normalized signal intensities and immunohistochemical protein expression patterns at each time point for KGF1, FGF2, and FGF10 are presented. The primary role of both KGF1 and FGF2 appeared to be in the proliferation and migration of keratinocytes. Whereas the role of KGF1 appeared to be exclusively concerned with increased proliferation and migration at the perforation site, the continued expression of FGF2, beyond perforation closure, suggested it has an additional role to play. FGF10 (KGF2), whilst possessing the highest sequence homologous to KGF1, has a different role in TM wound healing. The effect of FGF10 on keratinocytes in wound healing appeared to emanate from the connective tissue layer.

  View details for DOI 10.1007/s10735-010-9306-2

  View details for PubMedID 21136143

• The role of epidermal growth factor in the healing tympanic membrane following perforation in rats. Journal of molecular histology Santa Maria, P. L., Redmond, S. L., Atlas, M. D., Ghassemifar, R. 2010; 41 (6): 309-314

  Abstract

  Epidermal Growth Factor (EGF) has been identified as playing a critical role in the wound healing process. The objective of this study is to investigate the role that EGF plays in rat tympanic membrane (TM) wound healing using two techniques, microarray and immunohistochemistry. The tympanic membranes of rats were perforated using a sterile needle and sacrificed at time points during 2 weeks following perforation. The normalized signal intensities at the time points for EGF and associated genes are presented. The rat EGF mRNA did not change significantly between time points. Five associated proteins, including heparin-binding EGF-like growth factor were found to be differentially expressed above a two fold threshold at 12 h following perforation. EGF staining was found at low levels in the uninjured TM. Levels of EGF staining increased at 24 h in the basal keratinocyte layer, became diffusely elevated in the specimen at 36 h, before a second peak in staining of the keratinocyte layer at Day 4. The staining of EGF corresponds to its multiple roles in TM wound healing.

  View details for DOI 10.1007/s10735-010-9287-1

  View details for PubMedID 20967565

• Histology of the Healing Tympanic Membrane Following Perforation in Rats LARYNGOSCOPE Maria, P. L., Redmond, S. L., Atlas, M. D., Ghassemifar, R. 2010; 120 (10): 2061-2070

  Abstract

  The aim of this study was to provide a detailed cytological account on the healing tympanic membrane (TM) over 14 days and to complement existing research into TM wound healing.The study is a prospective cohort study of 19 male Sprague-Dawley (Rattus norvegicus) rats.Rat TMs were perforated using a sterile needle and sacrificed at time points during the 14 days following perforation.The healing of the TM resembles cutaneous wound healing except that the TM is unique in the lack of a supportive matrix beneath the regenerating epithelia. This prevents the influx of reparative cells and nutrients and the in growth of the usual fibroblastic reaction.TM wound healing contrasts with cutaneous wound healing in that keratinocytes are the first cells to close the wound and not the last. A keratin scaffold may not be important in the healing process. The malleus plays a crucial role in the healing of the TM and is the site of significant mitotic activity during the healing process. Migration across layers of the TM appears to account for the closure of the perforation.

  View details for DOI 10.1002/lary.20998

  View details for Web of Science ID 000282743100027

  View details for PubMedID 20824636

• Chronic tympanic membrane perforation: a better animal model is needed WOUND REPAIR AND REGENERATION Maria, P. L., Atlas, M. D., Ghassemifar, R. 2007; 15 (4): 450-458

  Abstract

  Developments in the treatment of chronic tympanic membrane perforation have been hindered by the lack of an ideal animal model. It is not appropriate to test such treatments on acute perforations as the majority of these heal spontaneously. An ideal animal model would be one that most closely resembles the human clinical situation. It should be inexpensive, readily available, and easy to create. There have been a number of attempts to create a chronic tympanic membrane perforation model with limited success. All published attempts at chronic tympanic membrane perforations have been reviewed and the limitations of each model are discussed. A number of areas for research exist for further developing a chronic tympanic membrane perforation model. These areas include a perforation model in the presence of bacteria and eustachian tube dysfunction. Understanding the molecular and genetic mechanisms of chronic otitis media and potential treatments will also be useful.

  View details for DOI 10.1111/j.1524-475X.2007.00251.x

  View details for Web of Science ID 000248754800003

  View details for PubMedID 17650087

• Neck dissection for squamous cell carcinoma of the head and neck. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Santa Maria, P. L., Sader, C., Preston, N. J., Fisher, P. H. 2007; 136 (4): S41-5

  Abstract

  To investigate the successes and failures of 172 patients receiving neck dissections for squamous cell carcinoma (SCC) managed through a multidisciplinary head and neck clinic and to observe factors in predicting failure (death with head and neck cancer or local regional recurrence) or local regional recurrence alone.A retrospective, 14-year surgical audit.The information from patient medical records was correlated with that of a database. Multivariate analysis was performed with the use of a logistic regression model.The most common site for head and neck SCC was the oral cavity (42%), with 17% of patients having tumors of unknown primary site. The disease-free survival probability was 76.7% at five years. Patients who were older at neck dissection, were nonsmokers, or who did not have radiotherapy to the primary site were more likely to die with head and neck cancer or to have local regional recurrence (P < 0.1). Patients with more radical neck dissections did not have better survival or recurrence outcomes. Lymphatic invasion appears to be the only important factor in predicting local regional recurrence alone (P = 0.1), of which 67% occurred within the first postoperative year.Patients with smoking-related SCC are likely to have a less aggressive disease. Adjuvant radiotherapy plays an important role in the treatment of patients with head and neck SCC. Follow-up, especially within the first postoperative year, is essential in managing head and neck SCC. Head and neck surgeons can confidently continue their practice away from more radical neck dissections.

  View details for PubMedID 17398340

• Cardiac surgery in Australian octogenarians: 1996-2001 16th RACS Inter ASC Meeting Hewitt, T. D., Santa Maria, P. L., Alvarez, J. M. WILEY-BLACKWELL PUBLISHING, INC. 2003: 749–54

  Abstract

  The number of octogenarians receiving cardiac surgery is increasing. Concerns regarding the outcomes and significant expense required to provide this service have not been addressed because no prospective medium term outcomes of Australian octogenarians have been published.Prospective analysis was undertaken of octogenarians having cardiac surgery from 1996 to 2001 in three hospitals of moderate case volume (400 patients per year) by: in-hospital audit and data acquisition, 1-year direct patient follow up in rooms, and a final follow up in late 2001 directly with the patient either in rooms or via telephone questionnaire.Sixty-four patients had cardiac surgery. All patients were severely disabled by symptoms (CCVS: III-IV, NYHA: III-IV) preoperatively, 14% were advised not to proceed with a surgical option but did so. Total operative in-hospital mortality was 6.3% (elective: 0%, urgent: 10.5%, P = 0.05), major complications were few 10.9% (seven patients; stroke: 1.6%, deep sternal infection: 1.6%, myocardial infarction: 1.6%, reoperation: 4.8%). At 1 year, despite 95% being free of significant cardiovascular symptoms (CCVS/NYHA: I-II), nearly one in five (19%) would not have proceeded with the surgery. However, at the final follow up (mean time: 2.8 years), freedom from cardiovascular symptoms remained high (95%), 94% remained independent and their quality of life was significantly better than before surgery. Although 59% suffered worsening of additional medical conditions, these conditions had a minor impact on their quality of life. Ninety-eight per cent would recommend cardiac surgery. Actuarial survival for all patients and for hospital survivors at 4 years was 67.9 +/- 4.1% and 74.2 +/- 4%, respectively.Medium-term follow up of Australian octogenarians who were offered cardiac surgery revealed that 94% remain independent and with an excellent quality of life. Age alone must not be a barrier to access to cardiac surgery.

  View details for Web of Science ID 000185196800016

  View details for PubMedID 12956792