Bio

Bio


Associate Director Stanford SPARK

Dr Peter Santa Maria is a surgeon scientist born and raised in Perth, Australia with a subspecialty interest in Otology, Neurotology and Skull Base Surgery. He attended medical school at The University of Western Australia before undertaking his residency in Otolaryngology, Head and Neck Surgery. He was the Neurotology and Skull Base Surgery fellow at Sir Charles Gairdner Hospital (2012), Western Australia before undertaking a three year instructorship at Stanford University in Otology, Neurotology and Skull Base Surgery (2015).

Clinically, Dr Santa Maria specializes in adult and pediatric surgery for hearing, balance and facial nerve disorders. He has a special interest in the management of cholesteatoma, acoustic neuroma and glomus tumor surgery as well as hearing implants, including cochlear implants. Dr Santa Maria has authored book chapters and published papers and continues his clinical research in these areas, particularly with a focus on hearing preservation.

Scientifically, Dr Santa Maria completed his PhD in the molecular biology of wound healing of the tympanic membrane at The University of Western Australia (2012). His research includes a novel treatment for chronic ear drum perforations was accelerated through the SPARK program at Stanford, winning the "Excellence in Stanford SPARK 2014" award, and then taken into a pharmaceutical start-up, Auration Biotech, aimed at bringing treatments for hearing loss into the clinic. Auration Biotech recently partnered with a large pharmaceutical company, Astellas, to bring the non-surgical treatment for ear drum repair into human clinical trials. He research has now expanded to include novel treatments for biofilms in chronic suppurative otitis media and growth factor therapy for oral wound healing.

Dr Santa Maria also co-invented a medical device which won the "Robert Howard Next Step Award in Medical Technology Innovation 2014", as part of Stanford's Biodesign program, that could keep patients warm during surgery. His team built and tested the first prototype before he led, as the Principal Investigator, the first in human clinical study where the device showed a three-fold benefit over the existing standard of care for preventing perioperative hypothermia. The device is now being further developed in another start-up, Flotherm, where he is working to bring the device to patients.

Clinical Focus


  • Otolaryngology

Academic Appointments


Administrative Appointments


  • Associate Director, Stanford SPARK (2018 - Present)
  • Director, SPARK Co-Lab (Perth) (2016 - Present)

Honors & Awards


  • Robert Howard Next Step Award in Medical Technology Innovation, Stanford Biodesign (2018)
  • 40 under 40 winner, Perth, Australia (2017)
  • Robert Howard Next Step Award in Medical Technology Innovation, Stanford Biodesign (2015)
  • William E. Eaglestein Award for Excellence in SPARK, Stanford SPARK (2014)
  • Research Grants / Awards: Principal Surgeon Scientist Award, Garnett Passe and Rodney Williams Memorial Foundation (2012-present)
  • Surgeon Scientist Award, Garnett Passe and Rodney Williams Memorial Foundation (2006-2008)
  • William Allnutt & May G Saw Medical Research Scholarship, The University of Western Australia (2005)
  • Simon Seow Memorial Prize in Public Health, The University of Western Australia (2000)
  • Western Australian Medical Students Society Person of the Year, Western Australian Medical Students Society (1999)

Boards, Advisory Committees, Professional Organizations


  • Board Member, Lions Hearing Foundation Board, Perth (2016 - 2017)
  • Chief of Scientific Advisory Board, Auration Biotech (2015 - Present)
  • Member, Ear Science Institute of Australia – Research Committee (2015 - 2017)
  • Member, American Academy of Otolaryngology, Head and Neck Surgery Hearing Committee (2015 - 2016)
  • Member, American Academy of Otolaryngology, Head and Neck Surgery Implantable Devices Committee (2015 - 2016)
  • Chief of Scientific Advisory Board, Flo-Therm (2014 - Present)
  • Member, Journal of Laryngology and Otology (Australian Supplement) - Editorial board (2014 - 2017)
  • Member, American Academy of Otolaryngology, Head and Neck Surgery Skull Base Surgery Committee (2014 - 2016)
  • Councillor, Australian Medical Association of Western Australia (2000 - 2000)
  • President, Western Australian Medical Students Society (2000 - 2000)

Professional Education


  • Fellowship:Sir Charles Gairdner Hospital (2012) WAAustralia
  • Instructorship, Stanford University, Otology, Neurotology, Skull Base Surgery (2015)
  • Residency:Royal Australasian College of Surgeons (2011) Australia
  • Fellowship, Sir Charles Gairdner Hospital, Otology, Neurotology, Skull Base Surgery (2012)
  • Residency:Sir Charles Gairdner Hospital (2005) WAAustralia
  • Internship:Sir Charles Gairdner Hospital (2002) WAAustralia
  • Residency / FRACS, The Royal Australian College of Surgeons, Otolaryngology, Head and Neck Surgery (2011)
  • Medical Education:University of Western Australia (2002) WAAustralia
  • MBBS, The University of Western Australia, Medicine / Surgery (2001)
  • PhD, The University of Western Australia (2012)

Research & Scholarship

Current Research and Scholarly Interests


Tympanic membrane regeneration
We developed a novel treatment for healing chronic tympanic membrane perforations which we have recently partnered with Astellas pharmaceuticals aiming for a clinical trial in the coming years. This treatment is delivered by hydrogel to heal the ear drum without surgery. We are also working on a therapy to prevent tympanic membrane wound healing that could be used as an alternative to pressure equalization tubes.

Biofilms in CSOM
We are collaborating to test new novel treatments that can treat pseudomonas and staphylococcus biofilms in chronic suppurative otitis media using a rodent model created in our lab.

Growth factor therapy for intra oral wound healing
Using rodent models for intra oral wound healing we are currently testing new grwoth factor therapy for healing in intra oral wounds with potential applications to prevent post tonsillectomy wound healing.

Medical devices
We have invented, prototyped and tested clinically a new medical device for maintaining perioperative normothermia with significant increased efficacy compared to the current standard of care

Clinical research
Evaluating outcomes of stereotactic radiation for vestibular schwanomma

Teaching

2018-19 Courses


Stanford Advisees


Publications

All Publications


  • 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 Web of Science ID 000392032000006

    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

  • 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-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

  • 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

  • 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

  • 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 DOI 10.1093/neuros/nyy407

    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 DOI 10.1177/0194599818775711

    View details for Web of Science ID 000443735400004

    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 DOI 10.1016/j.otc.2018.03.002

    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 DOI 10.1002/lary.27097

    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)
  • 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 DOI 10.1007/s00405-017-4810-6

    View details for Web of Science ID 000423551000030

    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 DOI 10.1186/s12871-017-0395-2

    View details for Web of Science ID 000407943000001

    View details for PubMedID 28800725

    View details for PubMedCentralID PMC5553896

  • 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 DOI 10.1159/000488386

    View details for Web of Science ID 000439389300001

    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