Conflict of Interest From Surviving to Thriving: Phrenic ...caduceushandouts.com/csm/2016/handouts/pedAPTA-2235753.pdf · innervate and reeducate her left hemi diaphragm after a

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From Surviving to Thriving:Phrenic Nerve Graft Surgery and Rehab.

Dr. Matthew Kaufman MD, FACS

The Institute for Advanced Reconstruction

Patricia West-Low, PT, MA, DPT, PCS

Children’s Specialized Hospital

Conflict of Interest

Neither Dr. Matthew Kaufman, nor Patricia West-Low have any conflict of interest in regard to this presentation

Objectives

• 1. Demonstrate awareness of appropriate candidates and the options for surgical re-innervation of the diaphragm muscle.

• 2. Identify and prioritize the multiple body systems requiring assessment and treatment post surgery.

• 3. Discuss appropriate and effective treatment strategies and sequencing.

• 4. Discuss the case of a 14-year-old athlete, surviving treatment for lymphoma, who underwent a sural to phrenic nerve graft and postsurgical rehabilitation, to re-innervate and reeducate her left hemi diaphragm after a tumor and subsequent ablation, crushed the phrenic nerve.

• Background– Introduction to pediatric phrenic nerve graft case

• Roles of the diaphragm– 3 systems– Multi-system function

• Phrenic Nerve Graft Surgery– Technical aspects– Algorithm for patient selection

• Post-operative PT examination– Participation– Function– System strengths/impairments

• Patient case– Surgical stand point– PT treatment

Back Story

• 8 year old female– C/O SOB

• Dx: “asthma exacerbation”

• Tx: Steroids & antibiotics

– Progressive SOB for 10 additional days• Seen in ER

– Oral steroids

– X-ray: Total left lung collapse

– CT Scan: 10 cm tumor on Thymus gland, also crushing L Phrenic N.

• Surgical excision of the tumor, and 2 years of chemo

Back Story

• Chemo drugs: • IV daunorubicin, IV doxorubicin, IV cyclophosphamide, IV

cytarabine and IV vincristine.• High dose methotrexate infusion followed by a leucovorin

"rescue" to save the liver and kidneys.• Intrathecal cytarabine and methotrexate.• SQ injections of cytarabine (at home)• IM Peg-Asparaginase.• oral mercaptopurine for twenty-eight days during one

phase and forty-two during another, and daily during the last eighteen months of treatment.

• oral thioguanine for fourteen days during one phase.• oral methotrexate once weekly during the last eighteen

months of treatment.

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Back Story

• “Ancillary Drugs”– High doses of oral prednisone for 35 continuous

days.

– High doses of oral dexamethasone twenty-eight straight days.

– For the last eighteen months of treatment, high doses of prednisone for five days each month.

– Multiple courses of antibiotics for upper respiratory infections

Pediatric Cancer Survivorship

• Physical Function/Activity Level

– Childhood Cancer Survivors (CCS) scored lower on tests of LE strength, the TUG and the 6MWT (Hoffman et al 2013)

– CCS nearly 2x more likely to report performance limitations (Ness et al 2009)

– CCS 1.4 x more likely to be inactive (Rueeg et al 2013)– Only 42% CCS reach healthy activity levels (Rueegg et al

2013)– High PA in CCS correlated with improved cardiovascular

profile (Slater et al 2014)– Factors predictive of decline in PA include female gender,

BMI >30 kg/m not completing high school and chronic musculoskeletal conditions(Wilson et al 2014)

Pediatric Cancer Survivorship

• Quality of Life Level

– Female survivors reports lower HRQOL in Physical and Emotional QOL subscales than males

– Female survivors ≥ 16 years of age scored lower on school QOL subscales than males

Cardio-toxicity of Chemo Drugs

– Cyclophosphamide as well as cytarabine & asparaginase have been associated with cardio-toxicity (Simbre et al 2005; Pai & Nahata, 2000)

– Cardio-toxicity may occur in 20% of patients treated with Doxorubicin and Daunorubicin (Pai & Nahata2000)

– Effects include asymptomatic ECG abnormalities, blood pressure changes, arrhythmias, myocarditis, pericarditis, Acute MI, Cardiac failure, cardiac shock and long term cardiomyopathy (Simbre et al 2005)

Complications of Left HemidiaphragmInactivity

• Dyspnea– Decreases breathing capacity by >1/3 (Elefteriades et

al 2008)• Reflux

– Decreased competence of the LES-Left crus can result in GERD (Eherer et al 2012)

– Reduced diaphragm function is a predictor of GERD (Pandolfino et al 2007)

– Micro-inhalation of reflux secretions is associated with pneumonia (Gaillet et al (2015)


• Scoliosis

– Chest wall deformity and scoliosis are common among children with repaired diaphragmatic defects (Peetsold et al 2009)

– Muscle asymmetry is part of the pathogenesis of late onset idiopathic scoliosis (Grivas et al. 2002)

– Increase risk of scoliosis after chest wall resection (Glotzbecker et al (2013)

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• Decreased balance and postural control

– The diaphragm has a feed forward role in postural stability (Gandevia et al (2002)

– Phrenic motor neurons contribute to both respiration and postural during challenges to posture (Hodges and Gandevia 2000)

Evidence Based Medicine

Best Available Evidence

Clinician Expertise

Patient Family Values

EBM

Roles of the Diaphragm

• Ventilation

• GI function (Pandolfino (2007); Feinsilver, 1944)

• Musculoskeletal structure/function (Grivas et al. 2002; Russell at al 2014)

• Venous return (Willeput 1984)

• Postural control (Hodges & Gandevia, 2000; Smith 2006; Hudson 2010;Hamaoui, 2010; Jansenns, 2013)

Summative Roles of the Diaphragm

The diaphragm is a respiratory muscle

The diaphragm assists the LES in inhibiting reflux

The diaphragm assists in elimination

The diaphragm impacts musculoskeletal alignment

The diaphragm assists in venous return

The diaphragm is a postural muscle

The diaphragm is a pressure regulator!!

Surgical Management of the Paralyzed Diaphragm: A Peripheral Nerve Approach

Matthew R. Kaufman, M.D., F.A.C.S.

The Institute for Advanced Reconstruction at The Plastic Surgery CenterShrewsbury, NJ

Co-Director, Center for Treatment of Paralysis & Reconstructive Nerve SurgeryJersey Shore University Medical Center

Neptune, NJ

Voluntary Clinical Assistant Professor of SurgeryDavid Geffen UCLA Medical Center

Los Angeles, CA

Clinical Assistant Professor of SurgeryDrexel University College of Medicine

Philadelphia, PA

Center for Treatment of Paralysis & Reconstructive Nerve Surgery

Jersey Shore University Medical Center, Neptune, NJwww.compellinghope.com

Regional, national, & international referral center Conditions treated

Peripheral nerve disorders (i.e. trauma, neuropathy) Sequelae of stroke & spinal cord injury

Diaphragmatic paralysis experience (Since 2007) More than 200 patients treated Well over 400 patients evaluated 4-5 new inquiries per week

Official Synapse Pacemaker Treatment Center (2014)

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Peripheral Nerve Disorders

Occipital Neuralgia/Migraine

Facial Paralysis

Cranial Nerve Injury

Brachial Plexus Injury

Diaphragm Paralysis

Upper/Lower Extremity Paralysis

Hand Injury

Perineodynia (Pudendal Neuralgia)

Lower Extremity Neuropathy

Footdrop

CNS Disorders

• Spinal Cord Injury

– Ventilator Dependency

– Pressure Sores

– Upper Extremity

• Stroke

– Dysphagia

– Hemiparesis

– Facial paralysis

• ALS

• Central Sleep Apnea

• CNS tumor

Diaphragm Anatomy

• Diaphragm

– Primary respiratory muscle

– Separates abdominal & thoracic cavities

– Contracts and flattens with inspiration

The Muscles of Respiration

Principal Respiratory MusclesIncrease thoracic dimensions

Diaphragm External intercostal Internal intercostal

Accessory Respiratory MusclesActivate during exercise, stress response, diaphragm paralysis

Sternocleidomastoid Scalenes Other: trapezius, serratus, latissimus, pectoralis

Diaphragm Innervation

• Phrenic Nerve

– Originates from C3-C5

– Motor innervation to diaphragm

– Sensory fibers

• Pleura

• Pericardium

• Abdominal components

Ventilator DependencyImpact On the Diaphragm

Compared 14 brain dead donors on PPV to 8 controls

18 hours of PPV causes marked atrophy

57% decrease Type 1 slow twitch

Active muscles atrophy faster

Inactivity leads to oxidative stress & proteolysis

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Diaphragmatic ParalysisEtiology

Peripheral

Iatrogenic Surgery

Anesthetic Blocks

Chiropractic

Trauma Blunt

Penetrating

Neuropathy / Neuromuscular

Viral / Idiopathic

Central

Spinal Cord Injury

Cervical Radiculopathy

Central Hypoventilation Syndrome

Tumors

Neurodegenerative conditions

Diaphragmatic Paralysis

Treatment Options Pulmonary rehabilitation

Diaphragm retraining therapy

CPAP/BiPAP

Mechanical ventilation

Plication of the diaphragm

Diaphragm Pacemaker

Phrenic Nerve Surgery

Diaphragm Muscle Replacement Surgery

Diaphragm Pacemakers• Indications

– Ventilator dependency• Cervical tetraplegia

• ALS

• Stroke

• Cord compression

• CNS tumor

• Central sleep apnea

– Off label use• Unilateral diaphragm paralysis

• Intractable hiccups

• Diaphragm flutter/myoclonus

Diaphragm PacemakerHistory

High freq phrenic stim Glenn 1976

Low freq phrenic stim Glenn 1984, Elefteriades 2002

Increased survival Carter 1993

Pacemaker + Nerve transfer Krieger 2000

Long term successful pacing Elefteriades 2002

Diaphragm stim Onders 2004, DiMarco 2005

Prospective comparison Hirschfeld 2008

Diaphragm PacemakerDemonstrable Benefits

Quality of life

Morbidity & mortality

Healthcare costs

Romero-Ganuza et al. Med Intensiva 2011

Diaphragm PacemakerWhen to Refer?

• As early as possible when non-invasive methods have failed or stalled (< 1 year)

• Especially when:– C1-3 or multilevel cervical tetraplegia

– EMG demonstrates uni- or bi-lateral phrenic neuropathy

• Even consider in certain less severe cases to “bridge to independent respiration”– Onders et al. J Trauma Acute Care Surg 2014

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Diaphragm PacemakerWhich Device?

Synapse Laparoscopic or VATS

Wires emerging (FDA application for implantable)

Direct muscle stimulation

Requires IRB for humanitarian use

Good Customer service

Not MRI compatible

Outdated technology

Demonstrable efficacy

Avery Cervical approach or VATS

All implantable

Transmission through applied antennae

Fully FDA approved

Mediocre Customer service (Improving)

Not MRI compatible

Outdated technology

Demonstrable efficacy

Diaphragm Pacemakers

• Up to 20% of attempted pacemaker implantation cases are aborted due to failure to stimulate

– Q: Why?

– A: Loss of phrenic nerve integrity

• Wallerian degeneration along the phrenic nerve(s)

• Progressive diaphragm muscle atrophy

Diaphragmatic Re-Innervation in Ventilator Dependent Patients with Cervical Spinal Cord Injury and Concomitant Phrenic Nerve Lesions

using Simultaneous Nerve Transfers and Implantable NeurostimulatorsKaufman et al. J Reconstr Microsurg, June 2015

Purpose A surgical treatment to reverse ventilator dependency

in pacemaker failures or absent phrenic nerve integrity

Demographics (N=14) Mean age=33 yrs. (range 10-66 yrs.) Injury level

C1 (2), C2 (2), C3 (1), C4 (2), Multilevel (7) ASIA A(13), ASIA B(1)

57% failed prior pacemaker attempt Time from injury to surgery: 34 months (range 6-90

months)

Diaphragmatic Re-Innervation…using Simultaneous Nerve Transfers and Implantable Neurostimulators

Kaufman et al. J Reconstr Microsurg, June 2015

Methods Inclusion Criteria

Cervical Tetraplegia

Ventilator Dependency (>6 mos.)

EMG/Nerve Conduction Studies Absent phrenic nerve conduction

No voluntary motor units detected in diaphragm

Available donor nerve(s) (i.e. spinal accessory, thoracodorsal, intercostal)

No active respiratory infection

Good cognitive function

Adequate family support & nursing care

Diaphragmatic Reinnervation…using Simultaneous Nerve Transfers and Implantable Neurostimulators


Methods Parameters for assessment Age, Sex

Level of injury, ASIA classification

Time from injury to treatment (mos.)

Time from treatment to re-innervation (mos.) Trans-telephonic monitoring (TTM)* biphasic activity

Average time pacing (hrs.)

*Auerbach A, Dobelle W. Transtelephonic monitoring of patients with implanted neurostimulators. The Lancet.1987;329(8526):224-5.



• Outcomes

– 13/14 (93%) successful diaphragm re-innervation

– Time from surgery to re-innervation: 7 mos. (range= 3-18 mos.)

– 8/13 (62%) achieved sustainable pacing (>1 hr. day)

• Mean= 10 hrs. (range >1-24 hrs.)

– Two patients recovered spontaneous respiratory activity (no pacemaker, no vent)

– Treatment resulted in a 20% (p<0.05) reduction in vent. dependency

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• Outcomes

– No intra-operative complications

– One patient developed bilateral effusions post-op requiring drainage

– Mean f/u=16 mos. (Range= 6-40 mos.)

Two month follow-up

66 y.o. male, C4,

ASIA A

Nine month follow-up



• Benefits of ventilator weaning are dramatic

• Current practice standards seem to under-utilize surgical options for weaning failures, or delay initiation

• Estimated 20-25% of potential pacemaker candidates will never be treated or will undergo failed procedures likely due to “double lesions”

• Consideration of a treatment algorithm that includes the option of phrenic nerve surgery when necessary

• Timing appears to be very critical for pacing success with nerve surgery

– 12 months or less is optimal



Limitations

Rapid and progressive diaphragm muscle atrophy = limited clinical success (incomplete weaning)

Electrical recovery without clinical recovery

Evaluation Of Current And Future Surgical Treatment Options For Diaphragmatic Paralysis And Ventilator Dependency In High

Cervical TetraplegiaKaufman et al. (ISCoS/ASIA 2015)

• How do we define progressive diaphragm atrophy?

– Electrodiagnostics: Absent voluntary motor units

– Ultrasound measurements: <2-3mm maximal thickness

Ventilator Weaning in SCIDealing with Progressive Diaphragm Atrophy

Current & Future Directions

• Prevention

– Early electrical stimulation to prevent or delay irreversible muscle atrophy

• Treatment

– Diaphragm muscle replacement surgery when irreversible degeneration

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Ventilator Weaning in SCICurrent & Future Directions

• Peripheral Nerve Stimulation• Preventing irreversible

muscle atrophy– J Neurophysiol, 2015

Ventilator Weaning in SCICurrent & Future Directions

Diaphragm Muscle Replacement Surgery

Transferring innervated, vascularized muscle (rectus abdominis/latissimus dorsi) into the atrophic diaphragm

Implanting a pacemaker into the transferred nerve-muscle unit

Diaphragm Replacement Surgery for SCI

.

First Diaphragm Replacement using Innervated Rectus with Pacemaker for SCI

5/8/2015

22 year-old female, C2-5, ASIA A (May 2014, MVAComplete ventilator dependency

Failed attempt at Synapse pacemaker

ICF Model Starting From the “End Game”

Participation Function Impairment

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“Physical therapy is a health profession whose primary purpose is the promotion of optimal health and function. This purpose is accomplished through the application of evidence-based principles to the processes of examination, evaluation, diagnosis, prognosis, and intervention to prevent or remediate impairments in body structures and function, activity limitations, participation restrictions or environmental barriers as related to movement and health.”APTA House of Delegates, 2012

Post-op Examination

• Integument

– Mobility of all scars in all directions

• How does CT mobility affect symmetry?

• Is scar tissue limiting chest wall expansion?

– Pain can have an impact on internal scar tethering ~(Esposito et al 2013)

– Scars can tether in remote areas ~ (Massery and Vicari 2015)

Post-Op Examination

• Musculoskeletal– Rib mobility

• Ribs 8-10 may be limited due to diaphragm pull• Ribs 4-7 may be limited due to intercostal coupling

– Spinal symmetry• Asymmetrical diaphragm pull

– Upper quarter screen• Effect of pre-surgical breathing pattern• Effects of rib mobility limitations

– Lower quarter screen • Effects of graft site sensory impairments (strength, power,

agility)

Post-op Examination

• Neuromotor– Diaphragm activation

• Look and feel• Supported and unsupported positions• Diaphragm excursion

– Diaphragm intercostal coupling• Watch for intercostal retraction • Lateral chest wall excursion

– Diaphragm/Intercostal muscular endurance• How long can they continue to use the involved side

diaphragm before it fatigues?

Post-Op Examination

• Cardio-pulmonary

– Pre-surgical hx

– Meds

– Breathing pattern, sequence and rate• At rest • With aerobic challenge

– O2 sats. during Cardio-pulm. challenges

– Get as close as possible to the activity they hope to return to

Post-op Examination

• GI System

– Reflux• Frequency

– Constipation• Frequency and ease of BM

– GI Meds?• Anti reflux• Laxatives

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Post-op Examination

• Postural stability

– Can the patient use their diaphragm to breathe while performing activities that challenge their postural stability?

– Timed Unilateral Stance, Pediatric Berg, TUG, Timed floor to stand, Timed shuttle run

Post-op Examination

• Sensory

– Proprioceptive awareness in the graft side Lower Chain

– Reactive postural control

– Unilateral stance eyes open versus eyes closed

• Diagnosis

– Medical Dx:• S/P phrenic Nerve graft

• S/P Lymphoma tx

– PT DX: • Impaired muscle performance Impaired ventilation

impaired aerobic capacity, impaired joint mobility,

• Muscle weakness

• Impaired sensory integrity

Treatment

• Prioritize and treat impairments as they relate to function

• Treat multiple impairments simultaneously

• Track the results of your treatments objectively

MS NM CP INT IO SP

Body Systems

Primary Pathology

Progression of impairments

Current Problems

Prioritize the Impairments

Tests And Measures

Interventions

Body Systems MS NM CP INT IO SP

PrimaryPathology

PhrenicNerve Paralysis

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Body Systems MS NM CP INT IO SP

Progression of impairments

3 1 2 5 4 6

Body Systems

MS NM CP INT IO SP

Current Problems

Shortening left side

Left Ribmobility

Right lateral trunk flexion

Left rotation

Decreased diaphragm Strength

Altered scapulo-humeral mechanics

Altered motor plan for diaphragm useAltered coupling of diaphragm and intercostals

Paralyzed left vocal fold

Altered balance and postural control

Impaired aerobic capacity

Impaired endurance

SOB with moderate exertion

O2 Sats in response to moderate cardio-pulmchallenges

Speed of HR recovery after cardio-pulmchallenge

Moderately decreased mobility of chest tube scarsSignificant adherence of tissues in the left lower leg

Reflux

Constipation

Persistent nausea

Alteredprop left ankle/LE

Altered Kinesth.Awareness

Left hemi-body

Body Systems

MS NM CP INT IO SP

Prioritize the Impairments

1 2 4 3 5 6

Body Systems

MS NM CP INT IO SP

Tests And Measures

Dynamometry

Lateral trunk flexion ROM

Shoulder ROM

DE, CWE, PBERG, TUG, TIMED SHUTTLE RUN

O2 sats.RR Rate/recovery

PFT

RefluxfrequencyBM frequencyMedication use

US EO/EC

MS NM CP INT GI SP

Interventions Rib 4-10 mobilizations

Yoga postures

Closed chain trunk, LE and UE strengthening

ConcentricCW and abdominal strength for airway clearance

PNF Controlledstretch to left diaphragm and left lateral CW –progressing from supported to unsupported

Inhibition of the right diaphragm

Yoga-postures and breathing practices

IMT on unstable surfaces while moving

Sport Specific NM retraining of inspiratory mmPNF to retrain scap-humeral rhythm

IMT-Breatherand Power breathe

O2 sat monitor during progressive challenges on Elliptical trainer, TM, simulated swimming

Ventilatorystrategies for swimming, throwing

CT mobilizationlateral and deep front line

IMT

Timing of meals with travel/sleep and PT

Proprioceptive re-training

Balance trainingTake Home Messages

• The diaphragm impacts multiple systems and functions-treat them all

• Watch and prevent for secondary impairments

• EBM has 3 parts, don’t ignore patient/family values

• Keep learning. Let your curiosity keep pulling you forward. BE A TRAILBLAZER!

Carvalho De Miranda Chaves, R., Suesadam M, Polisel, F et al. Respiratory Physiotherapy can increase lower esophageal sphincter pressure in GERD patients. Respir. Med., 2012; 106(12) 1794-9

de Blank PM, Ostrom QT, Rouse C, Wolinsky Y, Kruchko C, Salcido J, Barnholtz-Sloan JS Years of life lived with disease and years of potential life lost in children who die of cancer in the United States, 2009.Cancer Med. 2015 Jan 27 Deitz, Jean C.; Richardson, Pamela; Atwater, Sarah W.; Crowe, Terry K.; et al. Performance of normal children on the Pediatric Clinical Test of Sensory Interaction for Balance. Occupational Therapy Journal of Research, Vol 11(6), 1991, 336-356

Eherer, A.J., Netolitzky, F., Hogenauer, C. et al. Positive effect of breathing exercise on gastroesophageal reflux disease: a randomized, controlled study. Am J Gastroenterology. 2012;107(3):372-8

Elefteriades, J., Singh, M., Tang, M., et al. Unilateral diaphragm paralysis: etiology, impact, and natural history. J Cardivascu Surg, 2008;49(2):289-95

Esposito AJ, Heydrick SJ, Cassidy MR, et al. Substance P is an early mediator of peritoneal fibrinolytic pathway genes and promotes intra-abdominal adhesion formation. J Surg Res. 2013 May 1;181(1):25-31.

FEINSILVER , O. Mechanical Paralysis of the Left Hemidiaphragm Complicating Collapse Therapy in Pulmonary Tuberculosis 1944; http://publications.chestnet.org

Gaillet G1, Favelle O, Guilleminault L, de Muret A, Lemarie E, Lecomte T, Marchand-Adam S, Diot P. Gastroesophageal reflux disease is a risk factor for severity of organizing pneumonia. Respiration. 2015;89(2):119-26

Gandevia SC, Butler JE, Hodges PW, Taylor JL.Balancing acts: respiratory sensations, motor control and human posture. Clin Exp Pharmacol Physiol. 2002 Jan-Feb;29(1-2):118-21 Glotzbecker MP, Gold M, Puder M, Hresko MT .Scoliosis after chest wall

resection.J Child Orthop. 2013 Oct;7(4):301-7. Grivas TB, Samelis P, Chadziargiropoulos T, Polyzois B. Study of the rib cage deformity in children with 10 degrees-20 degrees of Cobb angle late onset idiopathic scoliosis, using rib-vertebra angles--aetiologic implications. Stud Health Technol Inform. 2002;91:20-4. . Hamaoui, A, Hudson, AL, Laviolette, L, Nierat, MC, Do, MC, Similowski, T. Postural disturbances resulting from unilateral and bilateral diaphragm contractions: a phrenic nerve stimulation study. J Appl Physiol . 2014 Oct 15;117(8):825-32. Hodges, PW, Gandevia, SC. Activation of the human diaphragm during a repetitive postural task. J Physiol. 2000 Jan 1;522 Pt 1:165-75. Hoffman, MA. Mulroony, D.A., Steinberger, J., Lee, J., Baker, K.S., Ness, K.K. Deficits in Physical Function among young childhood cancer survivors. J Clin. Oncol. 2013;31(22) Jannsens, L. , Brumagne, S. , McConnell AK, Claeys K, Pijnenburg M, Burtin C, Janssens W, Decramer M, Troosters T. Proprioceptive changes impair balance control in individuals with chronic obstructive pulmonary disease. PLoS One. 2013;8(3) Kaufman MR, Elkwood AI, Colicchio AR, CeCe J, Jarrahy R, Willekes LJ, Rose MI, Brown D.Functional restoration of diaphragmatic paralysis: an evaluation of phrenic nerve reconstruction. Ann Thorac Surg. 2014 Jan;97(1):260-6. Kaufman MR, Elkwood AI, Rose MI, Patel T, Ashinoff R, Fields R, Brown D.Surgical treatment of permanent diaphragm paralysis after interscalene nerve block for shoulder surgery.Anesthesiology. 2013 Aug;119(2):484-7 Kaufman MR, Willekes LJ, Elkwood AI, Rose MI, Patel TR, Ashinoff RL, Colicchio AR.Diaphragm paralysis caused by transverse cervical artery compression of the phrenic nerve: the Red Cross syndrome. Clin Neurol Neurosurg. 2012 Jun;114(5):502-5 Kaufman MR, Elkwood AI, Rose MI, Patel T, Ashinoff R, Saad A, Caccavale R, Bocage JP, Cole J, Soriano A, Fein E.Reinnervation of the paralyzed diaphragm: application of nerve surgery techniques following unilateral phrenic nerve injury. Chest. 2011 Jul;140(1):191-7 Mantilla, C.B., Sieck, G.C. Impact of Diaphragm Muscle Fiber Atrophy on Neuromotor Control. Respir Physiol Neurobiol. (2013) 189(2) Massery M, Hagins M, Stafford R, Moerchen V, Hodges PW.

Effect of airway control by glottal structures on postural stability. J Appl Physiol . 2013 Aug 15;115(4):483-90 Miller L, Vegesna A, Kalra A, Besetty R, Dai Q, Korimilli A, Brasseur JG.New observations on the gastroesophageal antireflux barrier. Gastroenterol Clin North Am. 2007 Sep;36(3):601-17 Ness KK1, Hudson MM, Ginsberg JP, Nagarajan R, Kaste SC, Marina N, Whitton J, Robison LL, Gurney JG. Physical performance limitations in the Childhood Cancer Survivor Study cohort. J Clin Oncol. 2009 May 10;27(14):2382-9. Nobre e Souza, M.A., Lima, M.J. Martins, G.B. et al. Inspiratory muscle training improves antireflux barrier in GERD patients. Am J Gastrointest Liver Physiol. 2013; 305(11);G862-7 Pai VB, Nahata MC.Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention. Drug Saf. 2000 Apr;22(4):263-302. . Pandolfino JE1, Kim H, Ghosh SK, Clarke JO, Zhang Q, Kahrilas PJ High-resolution manometry of the EGJ: an analysis of crural diaphragm function in GERD. Am J Gastroenterol. 2007 102(5):1056-63. Peetsold MG., Heij HA, Kneepkens CM, Nagelkerke AF, Huisman J, Gemke RJ The long-term follow-up of patients with a congenital diaphragmatic hernia: a broad spectrum of morbidity. Pediatr Surg Int. 2009 Jan;25(1):1-17. Raghuraj, P. & Telles, S. (2008) Immediate effect of specific nostril manipulating yoga breathing practices on autonomic and respiratory variables. Applied Psychopysiological Biofeedback, 33(2):65-75 Rueegg, C.S., Gianinazzi, M.E., Michel, G. et al.. Do childhood cancer survivors with physical performance limitations reach healthy activity levels? Pediatric Blood Cancer. 2013;60(10) 1714-20 Russell KW, Barnhart DC, Rollins MD, et al. Musculoskeletal deformities following repair of large congenital diaphragmatic hernias.J Pediatr Surg. 2014 Jun;49(6):886-9. Scalabre A, Parot R, Hameury F, et al.Prognostic risk factors for the development of scoliosis after chest wall resection for malignant tumors in

children.J Bone Joint Surg Am. 2014 Jan 15;96(2) Simbre VC1, Duffy SA, Dadlani GH, Miller TL, Lipshultz SE Cardiotoxicity of cancer chemotherapy: implications for children. Paediatr Drugs. 2005;7(3):187-202. Slater, M. E., Ross, J. A., Kelly, A. S., Et al. Physical activity and cardiovascular risk factors in childhood cancer survivors. Pediatric Blood Cancer. 2014 Smith MD, Chang AT, Seale HE, Walsh JR, Hodges PW Balance is impaired in people with chronic obstructive pulmonary disease. Gait & Posture. 2010 Apr;31(4):456-60. Willeput R, Rondeux C, De Troyer A Breathing affects venous return from legs in humans. J Appl Physiol Respir Environ Exerc Physiol. 1984 Oct;57(4):971-6. Wilson, C. L., Stratton, K., Leisenring, W.L., et al. Decline in physical activity level in the Childhood Cancer Survivor Study cohort. Cancer Epidemiol Biomarkers Prev. 2014; 23 (8):1619-27 Wolach O, Ram R.Adolescents and young adults with non-Hodgkin'slymphoma: slipping between the cracks. Acta Haematol. 2014;132(3-4):279-91. Woolery, M. et al. A constipation assessment scale for use on pediatric oncology Journal of Pediatric Oncology Nursing March 2006 23: 65-74

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Conflict of Interest From Surviving to Thriving: Phrenic ...caduceushandouts.com/csm/2016/handouts/pedAPTA-2235753.pdf · innervate and reeducate her left hemi diaphragm after a