OMB No. 0925-0001 and 0925-0002 (Rev. 03/2020 Approved Through 02/28/2023)

NAME: Mary C. Theroux, MD

eRA COMMONS USER NAME (credential, e.g., agency login): mtheroux

POSITION TITLE: Pediatric Anesthesiologist, Professor of Anesthesiology and Perioperative Medicine

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)

A.        Personal Statement
 

Research: I have authored and co-authored approximately 60 peer-reviewed international publications, in addition to several book chapters and consensus statements. I was the recipient of a COBRE grant (target investigator) to study the peripheral nervous system in Cerebral Palsy (2003 to 2005) in addition to several intramural funds to study translational research in children with cerebral palsy.

Approximately from year 2010, I have been focusing on clinical and translational research in children and adults with affected by skeletal dysplasia. I have a greater interest in patients with mucopolysaccharidosis especially patients affected by Morquio Syndrome. My interest is further fueled by the complex nature of their airway difficulties and the unique challenges that they pose to the Anesthesiologists. At A.I DuPont hospital for children we care for over 80 patients with Morquio syndrome and this number is steadily increasing. This is the largest Morquio population found in the world at a single center and makes our children’s hospital (which also cares for adult Morquio patients) a unique place to not only provide centralized care, but also study this patient population. Since 2010, my publications have focused on clinical work related to skeletal dysplasia, predominantly related to Morquio patients. I am consulted by national and international Institutes to provide advice on the anesthetic care of Morquio patients ever since we discovered and corrected the tracheal abnormality that resulted in the near demise of a young Morquio patient in 2015. One of my career goals is to disseminate the information we now have, among both the scientific world and the Morquio patient world. In doing so I have been closely working with the PI of this proposed grant, Dr. Shunji Tomatsu and am aptly positioned to be a co-investigator

B.        Positions and Honors
 

UProfessional Employment history

1989-present   Staff Appointment in Pediatrics and Anesthesiology, Alfred I. duPont Hospital for Children, Wilmington, Delaware

1990                            Clinical Instructor, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

1994                            Clinical Assistant Professor, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

1999                            Clinical Associate Professor, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

2006                            Associate Professor, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

2009                            Professor, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania

2014-2019                   Director of Research, Department of Anesthesiology and Perioperative Medicine

UBoard Certification

1986                            Diplomate, American Board of Pediatrics

1990                            Diplomate, American Board of Anesthesiology

UHonors and Awards

1986                American Academy of Pediatrics

1989                American Society of Anesthesiology

1989                International Anesthesia Research Society

1989                Delaware Society of Anesthesiology

1990                Critical Care Society

1990                Society of Pediatric Anesthesia

1990                Diplomate, American Board of Anesthesiology

1992                Second place award at the Resident Research Award ceremonies sponsored by the Department of Medical Education, Medical Center of Delaware.

2001                Consultant - Malignant Hyperthermia Association of United States

2006                Elected member ‘Association of University Anesthesiologists’ (AUA)

2008                Malignant Hyperthermia Hot Line partnership award, received at the MHAUS recognition    reception at the ASA meeting, Orlando, Fl, on Oct 20, 2008

2017                Anesthesiologist, Skeletal dysplasia team, Nemours/A.I duPont hospital for children.

C.        Contributions to Science

1.   Safer anesthetic care of Morquio A patients (Airway Management).  During the last 10 years I have      focused on making the anesthetic care of Morquio A patients safer. Among the MPS patients, Morquio A patients are exposed to surgery and anesthesia most frequently. There are similarities between the anesthetic difficulty of Morquio patients and other MPS patients. Moreover, some similarities related to the airway management are common among all skeletal dysplasia patients. The unique aspect of the Morquio A patients is the tracheal abnormalities seen as the patients reach adolescent and teenage years. These abnormalities are severe and likely contributed to the early demise of many Morquio A patients. However, knowledge and awareness among the patients and medical care providers was lacking until the early part of 2015. At Nemours A.I DuPont hospital for children, we provide centralized care for children with skeletal dysplasia. We have approximately 80 patients with Morquio A and therefore has one of the world’s largest cohort of Morquio A patients. Given the frequency of surgical procedures they undergo, it became an urgent and compelling need to find ways to manage their anesthesia care safely. I have been conducting studies to examine the anesthetic difficulty and in so doing, have described ways to minimize risk from anesthesia in Morquio A.

1. Doherty C, Averill LW, Theroux M, Mackenzie WG, Pizarro C, Mason RW, Tomatsu S. Natural history of Morquio A patient with tracheal obstruction from birth to death. Molecular Genetics and Metabolism. 2018: 14: 59-67
2. Tomatsu S, Averill LW, Sawamoto K, Mackenzie WG, Bober MB, Pizarro C, Goff CJ, Xie L, Orii T, Theroux M: Obstructive airway in Morquio A syndrome, the past, the present and the future. Mol Genet Metab:  2016 ;117(2):150-6
3. Pizarro C, Davies RR, Theroux M, Spurrier EA, Averill LW, Tomatsu S. Surgical Reconstruction for Severe Tracheal Obstruction in Morquio A Syndrome: Ann Thorac Surg. 2016 ;102(4):329-31
4. Theroux MC, Nerker T, Ditro C, Mackenzie WG: Anesthetic care and perioperative complications of children with Morquio syndrome. Paediatr Anaesth. 2012 ;22(9):901-7

2.   Preventing spinal cord injury during anesthesia and surgery in MPS patients. Incidence of spinal cord injury has been a hot topic in the MPS community and even more so in the Morquio A community. There have been several incidents of spinal cord infarction/injury in MPS patients which have occurred during surgery involving upper or lower extremities (NOT SPINE) . Only three such cases have been reported due to cases having been heavily litigated. With the help of our Orthopedic surgeon who heads the skeletal dysplasia program, I have sought to increase awareness of the risk of spinal cord injury the MPS patients face while anesthetized for a non-spine procedure. The only recourse to preventing such occurrences is to monitor the integrity of the spinal cord during such procedures, which has become our standard practice. However, this is not so in the majority of other hospitals in the country. There has been an ‘alert’ placed by the ‘Wake Up Safe’ organization which is an Anesthesiology led mult institutional effort to minimize risk of anesthesia. We have consistently provided consultation to many hospitals around the country and abroad on when to monitor the spinal cord for MPS patients and published literature whenever the opportunity arose.

1. Joel Charrow, Tord D. Alden, Catherine Ann R. Breathnach, Geoffrey P. Frawley, Christian J. Hendriksz ,Bianca Link, William G. Mackenzie,, Renzo Manara, Amaka C. Offiah, Martha L. Solano, Mary Theroux: Diagnostic evaluation, monitoring, and perioperative management of Spinal cord compression in patients with Morquio syndrome: Molecular Genetics and Metabolism. 2015. (114) 11–18.
2. Drummond JC, Krane EJ, Tomatsu S, Theroux MC, .Lee RR,: Paraplegia after epidural-general anesthesia in a Morquio patient with moderate thoracic spinal stenosis: Can J Anesth 2014. 2015 Jan;62(1):45-9
3. Guirish A. Solanki, Kenneth W. Ma rtin, Mary C. Theroux,Christina Lampe,  Klane K. White,Renée Shediac,Christian G. Lampe,Michael Beck, William G. Mackenzie, Christian J. Hendriksz, Paul R. Harmatz: Spinal involvement Mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A Syndrome): presentation, diagnosis and management: Journal of Inherited Metabolic Diseases: 2013, 36(2):339-55.
4. DiCindio S, Theroux M, Shah S, Miller F, Dabney K, Brislin RP, Schwartz D. Multimodality monitoring of transcranial electric motor and somatosensory-evoked potentials during surgical correction of spinal deformity in patients with cerebral palsy and other neuromuscular disorders. Spine. 2003:15:28 (16): 1851-5.

3.   Safer anesthetic management of ‘little people’ (‘Little People’ refers to the population of patients with skeletal dysplasia – It is a term used widely in United States). In the more recent years, I have been focused on the anesthetic care of all forms of skeletal dysplasia.  From an anesthetic standpoint, they often do not belong to any particular anesthetic society; in other words the Society of Pediatric Anesthesia and the other major anesthesia organizations have not quite realized (yet) the risk of anesthetic care these patients pose. This is slowly changing and I believe that my contribution to increasing the awareness of their anesthetic risk has been substantial as shown by the publications below.

1. Theroux MC, Lopez M, Olszewsky PJ, DiCindio S, Arai L, Ditro C, Bober MB, Olla OO, Uejima T, West DW, Mackenzie WG5. Metatropic dysplasia-a skeletal dysplasia with challenging airway and other anesthetic concerns. Paediatr Anaesth. 2017: 27(6):596-603
2. White KK, Bompadre V, Goldberg MJ, Bober MB, Cho TJ, Hoover-Fong JE, Irving M, Mackenzie WG, Kamps SE, Raggio C, Redding GJ, Spencer SS, Savarirayan R, Theroux MC; Skeletal Dysplasia Management Consortium: Best practices in peri-operative management of patients with skeletal dysplasias. Am J Med Genet A. 2017, 173(10):2584-2595
3. Brenn BR1, Theroux MC, Shah SA, Mackenzie WG, Heinle R, Scavina MT. Critical Airway Stenosis in an Adolescent Male With Pompe Disease and Thoracic Lordosis: A Case Report. A A Case Rep. 2017 (173): 10: 2584-2595
4. Eiszner JR, Atanda A Jr, Rangavajjula A, Theroux M: A case series of peripheral nerve blocks in pediatrics and young adults with skeletal dysplasia. Paediatr Anaesth:2016 May;26(5):553-6.

 4.   Safer anesthetic care of children with cerebral palsy

      Cerebral palsy is the commonest neurological disorder in children and when I started my career in Pediatric Anesthesiology I realized there was virtually no medical information published to help anesthetize patients with cerebral palsy safely. At A.I Dupont hospital for children we care for a large number of patients with cerebral palsy and therefore surgical procdures in such patients were common. Some procedures are much more extensive in nature in comparison to similar procedures performed in otherwise normal children. I, along with the help of Nemours Biomedical Research started a series of studies to help answer questions related to their clinical care. The following publications are a result of this effort.

1. DiCindio S, Arai L, McCulloch M, Sadacharam K, Shah SA, Gabos P, Dabney K, Theroux MC. Clinical relevance of echocardiogram in patients with cerebral palsy undergoing posterior spinal fusion.Paediatr Anaesth. 2015 (25) 840-845
2. Theroux MC, Oberman KG, Lahaye J, Boyce B, DuHadaway D, Miller F, Akins RE. Dysmorphic neuromuscular junctions associated with motor ability in cerebral palsy 2005, . Muscle Nerve 32:626-632, 2005
3. Brenn RB, Theroux MC, Dabney KW, Miller F. Clotting parameters and thromboelastography in children with neuromuscular and idiopathic scoliosis undergoing spinal fusion. Spine , 2004: 29: 10-14
4. Theroux MC, Akins RE, Barone C, Boyce B, Miller F, Dabney KW. Neuromuscular junctions in cerebral palsy. Presence of extrajunctional acetylcholine receptors. Anesthesiology. 2002: 96:330-5

5.   How to perform ‘One Lung Ventilation’ safely with minimum injury to the lung. One lung ventilation is an anesthetic technique used to facilitate surgery on structures in the thoracic cavity when the lung is ‘in the way’. One such procedure is anterior spine fusion especially when performed thoracoscopically. Anesthesiologists have been performing this technique by intentionally blocking ventilation to one lung without much recourse to dealing with resultant side effects. Following a cardiac arrest during such a procedure I was on a quest to reduce the inflammatory injury from collapsing a lung and reexpanding it later. The following publications support my effort in answering this question. 

1. Theroux MC, Olivant A, Lim D, Bernardi JP, Costarino AT, Shaffer TH, Miller TL. Low Dose Methylprednisolone Prophylaxis to Reduce Inflammation During One Lung Ventilation. Paediatr Anaesth. 2008 Sep; 18 (9):857-64.
2. Theroux MC, Olivant Fisher A, Horner LM, Rodriguez ME, Costarino AT, Miller TL, Shaffer TH. Protective ventilation to reduce inflammatory injury from one lung ventilation.  Paediatr Anaesth: April, 2010: 20(4):356-364
3. Rahul Bhatia, Thomas H. Shaffer, Jobayer Hossain, PhD; Alicia Olivant Fisher, MS, Liana M. Horner,  M. Elena Rodriguez, Scott Penfil, Mary C Theroux. Surfactant administration prior to one lung ventilation: physiological and inflammatory correlates in a piglet model, Pediatr Pulmonol. 2011 Nov;46(11):1069-78
4. Olivant Fisher A, Husain K, Wolfson MR, Hubert TL, Shaffer TH, Theroux MC. Hyperoxia during one lung ventilation: inflammatory and oxidative responses. Pediatr Pulmonol. 2012: 47(10):979-986

Complete List of Published Work in My Bibliography:

https://pubmed.ncbi.nlm.nih.gov/?term=THEROUX+M&sort=date

D.        Additional Information: Research Support and/or Scholastic Performance

Ongoing Support: A longitudinal study of skeletal dysplasia: This study enrolls all skeletal dysplasia patients cared for at Nemours/A.I DuPont Hospital for children. No extramural funds have been requested for this study and the study is supported by the Department of Anesthesiology and the Department of Orthopedics.

Role: PI

2016-

NIH: (Research Project) External Grant: Non-invasive functional assessment and pathogenesis of Morquio A:   (R01) R01 HD102545-01A1 2021: Grant. Mary C Theroux. Role: Co-Investigator.

Total Cots; $2,906,407.00: Role: Co-Investigator

Completed Projects

1. Does methylprednisolone confer additional benefits when a protective ventilation strategy is employed during one lung ventilation

16-02376-006, Nemours Biomedical Research, 10/1/2009 to 9/30/2011.       $119,698

Role: PI

This study in an animal model of one lung ventilation seeks to determine whether the use of methylprednisolone in conjunction with protective ventilation provides for additional benefits over methylprednisolone or protective ventilation alone. The long-term goal of the study is to develop clinical interventions and therapeutic strategies to minimize pulmonary injury during one-lung ventilation.

2. Peripheral Nervous System in Cerebral Palsy

      W20-8739, Nemours/NIH IP 20RR020173-0, (COBRE grant. 7/1/2003 to 12/31/2005) followed by       Nemours Funds until 12/31/2006

      Role: Target Investigator

      Neuromuscular junctions in children with cerebral palsy: Structural and functional pathophysiology

This study examined the pathophysiology of the abnormal neuromuscular junction seen in some of the children with cerebral palsy. It also involved using a muscle relaxant (succinylcholine) commonly used during anesthesia and studying the effect, namely, the release of potassium, as a result of the abnormal interaction of these AChRs with this particular muscle relaxant.

3. Extra-junctional acetylcholine receptors in cerebral palsy:  Relationship to spasticity and muscle type

      W20-8642, Nemours Biomedical Research, 1/1/2000 to 6/30/2003

      Role: PI

This study examined the AChRs and their distribution in relationship to the level of gross motor function, which was assessed by evaluating the ambulatory status of these patients.

4. Assessment of Lung Injury during One Lung Ventilation and Evaluation of Treatment Regimes

      16-02376-003, Nemours Biomedical Research, 7/1/2006 to 12/31/2008.

      Role: PI

This is the pre-clinical study upon which our translational research for K23 grant proposal is based. A porcine model of one lung ventilation in pediatrics was used to determine the extent of injury sustained during one lung ventilation and to study treatment regimes, the first of which is the methylprednisolone trial. Other treatment regimens include high frequency oscillatory ventilation applied to the collapsed lung        and use of a protective ventilation strategy to minimize inflammation from one lung ventilation.

4. Low dose methylprednisolone to reduce inflammation from one lung ventilation in children

16-02376-005, Nemours Biomedical Research, 10/1/2008 to 10/1/2010.

Role: PI

This study in children is the translational research component following our pre-clinical studies assessing lung injury from one lung ventilation in a juvenile piglet model.

5. Prophylactic Administration of Calfactant to minimize inflammation from One Lung Ventilation NBR2006-   004, Nemours Biomedical Research; 4/1/2008 to 9/31/2009.

      Role: PI

This is a pre-clinical study for treatment of inflammation from one lung ventilation in our piglet model. Our goal is to examine the effect of calfactant in minimizing inflammatory injury when given to the collapsed lung prior to one lung ventilation.  This arm of the study also examines a group of animals who received lower inspired oxygen under the same study conditions to investigate possible oxidative injury from high inspired oxygen used during one lung ventilation.

6. Development of neuromuscular junctions in children with cerebral palsy.

RO3: HD051738-01

7/1/2007 - 6/30/2009

Role: Collaborator. Effort < 3%.