Smilo v. Secretary of Health and Human Services

In the United States Court of Federal Claims

OFFICE OF SPECIAL MASTERS

Filed: May 15, 2023

*************************

GERTRUDE SMILO, Administratix *

of the estate of JOSEPH G. SMILO, * PUBLISHED

deceased, *

*

Petitioner, * No. 18-1585V

*

v. * Special Master Nora Beth Dorsey

*

SECRETARY OF HEALTH * Entitlement; Influenza (“Flu”) Vaccine;

AND HUMAN SERVICES, * Myasthenia Gravis; Causation-in-Fact;

* Significant Aggravation.

Respondent. *

*

*************************

Jeffrey A. Golvash, Golvash & Epstein, LLC, Pittsburgh, PA, for Petitioner.

Naseem Kourosh, U.S. Department of Justice, Washington, DC, for Respondent.

DECISION 1

I. INTRODUCTION

On October 12, 2018, Gertrude Smilo (“Petitioner”), Administratix of the Estate of

Joseph G. Smilo (“Mr. Smilo”), deceased, filed a petition for compensation under the National

Vaccine Injury Compensation Program (“Vaccine Act” or “the Program”), 42 U.S.C. § 300aa-10

1

Because this Decision contains a reasoned explanation for the action in this case, the

undersigned is required to post it on the United States Court of Federal Claims’ website and/or at

https://www.govinfo.gov/app/collection/uscourts/national/cofc in accordance with the E-

Government Act of 2002. 44 U.S.C. § 3501 note (2018) (Federal Management and Promotion of

Electronic Government Services). This means the Decision will be available to anyone with

access to the Internet. In accordance with Vaccine Rule 18(b), Petitioner has 14 days to

identify and move to redact medical or other information, the disclosure of which would

constitute an unwarranted invasion of privacy. If, upon review, the undersigned agrees that the

identified material fits within this definition, the undersigned will redact such material from

public access.

et seq. (2018) 2 alleging that Mr. Smilo developed myasthenia gravis which was caused-in-fact,

or in the alternative, significantly aggravated by an influenza (“flu”) vaccination administered on

October 17, 2016. Petition at Preamble (ECF No. 1). Respondent filed his Rule 4(c) Report on

October 30, 2019, arguing against compensation, stating “this case is not appropriate for

compensation under the [Vaccine] Act.” Respondent’s Report (“Resp. Rept.”) at 2 (ECF No.

25).

After carefully analyzing and weighing the evidence presented in this case in accordance

with the applicable legal standards, the undersigned finds that Petitioner has failed to provide

preponderant evidence that Mr. Smilo’s myasthenia gravis was caused by or significantly

aggravated by his flu vaccination. Thus, Petitioner has failed to satisfy her burden of proof under

Althen v. Sec’y of Health & Hum. Servs., 418 F.3d 1274,at 1278 (Fed. Cir. 2005) and Loving v.

Secretary of Health & Human Services, 86 Fed. Cl. 135, 142-44 (2009). Accordingly, the

petition shall be dismissed.

II. ISSUES TO BE DECIDED

The parties stipulate that Mr. Smilo received a flu vaccination on October 17, 2016, at the

age of 63, and that he died on April 6, 2017. Joint Submission, filed Aug. 4, 2022, at 1 (ECF No.

59). His death certificate identified “his ‘immediate cause’ of death as liver failure and

hepatocellular carcinoma [(“HCC”)].” Id. Other significant conditions that contributed to his

death but did not result “‘in the underlying cause’ of death [were] myasthenia gravis, septic

shock, and multiple organ failure.” Id. They further agree that Mr. Smilo “suffered from

myasthenia gravis.” Id.

As a threshold matter, the parties dispute whether Petitioner meets the severity

requirement under Vaccine Act § 11(c)(1)(D). 3 Petitioner’s Motion for Ruling on the Record

(“Pet. Mot.”), filed Aug. 5, 2022, at 23 (ECF No. 60); Resp. Response to Pet. Mot. (“Resp.

Response”), filed Sept. 21, 2022, at 13-21 (ECF No. 62); Pet. Reply to Resp. Response (“Pet.

Reply”), filed Oct. 5, 2022 (ECF No. 63). Specifically, the parties dispute whether Petitioner has

shown Mr. Smilo “(ii) died from the administration of the vaccine, or (iii) suffered such illness,

disability, injury, or condition from the vaccine which resulted in inpatient hospitalization and

surgical intervention.” § 11(c)(1)(D)(ii)-(iii); see Joint Submission at 2; Pet. Mot. at 23; Resp.

Response at 13-21; Pet. Reply at 1-4.

There is also a factual dispute. The parties disagree as to the onset of Mr. Smilo’s

myasthenia gravis, specifically whether onset was before or after the flu vaccination

2

The National Vaccine Injury Compensation Program is set forth in Part 2 of the National

Childhood Vaccine Injury Act of 1986, Pub. L. No. 99-660, 100 Stat. 3755, codified as amended,

42 U.S.C. §§ 300aa-10 to -34 (2018). All citations in this Decision to individual sections of the

Vaccine Act are to 42 U.S.C. § 300aa.

3

Although this issue was not mentioned in the parties’ joint submission, the parties addressed it

in their respective briefs, and thus, the undersigned finds it is appropriate to resolve the issue.

2

administered on October 17, 2016. Joint Submission at 1; Pet. Mot. at 9, 17; Resp. Response at

21.

Regarding causation, the parties dispute whether Petitioner has proven by preponderant

evidence that the flu vaccination can cause or significantly aggravate myasthenia gravis, and that

it did so here. 4 Joint Submission at 1. Further, they dispute whether Petitioner has proven by

preponderant evidence the standards articulated in Althen/Loving. Pet. Mot. at 23; Resp.

Response at 13. Lastly, the parties dispute whether Petitioner has proven by preponderant

evidence that Mr. Smilo’s death was the result of his flu vaccination. Joint Submission at 2.

III. PROCEDURAL HISTORY

Petitioner filed a petition on October 12, 2018, followed by medical records on

November 30, 2018 and an expert report from Dr. George Alan Small on December, 3, 2018.

Petition; Pet. Exhibits (“Exs.”) 1-15. On September 27, 2019, Petitioner filed additional medical

records. Pet. Exs. 16-17. Respondent filed his Rule 4(c) Report, arguing against compensation

on October 30, 2019. Resp. Rept. at 2.

From April 2020 to August 2021, Petitioner filed expert reports from Dr. James N.

DeAngelo and Dr. Small, medical records, and affidavits, and Respondent filed expert reports

from Dr. Eric Lancaster. Pet. Exs. 18, 45-47, 55, 61-62; Resp. Exs. A, C-D. Thereafter, this

case was referred to alternative dispute resolution (“ADR”) in September 2021, but by

November, this case was removed from ADR proceedings. Order Referring Case to ADR dated

Sept. 23, 2021 (ECF No. 43); Order Concluding ADR Proceedings dated Nov. 2, 2021 (ECF No.

44).

This case was reassigned to the undersigned on February 7, 2022. Notice of

Reassignment dated Feb. 7, 2022 (ECF No. 47). The undersigned held a status conference on

February 17, 2022 to discuss next steps. Order dated Feb. 17, 2022 (ECF No. 48). On March

21, 2022, Respondent indicated he was not amenable to settlement discussions. Resp. Joint

Status Rept., filed Mar. 21, 2022, at 1 (ECF No. 49). The parties indicated that they wished to

file supplemental expert reports before resolving entitlement through a ruling on the record. Id.

Petitioner filed a supplemental expert report from Dr. Small on March 13, 2022, and

Respondent filed a supplemental expert report from Dr. Lancaster on June 17, 2022. Pet. Ex. 63;

Resp. Ex. E. In August 2022, Petitioner filed her motion for a ruling on the record. Pet. Mot.

Respondent filed his response on September 21, 2022, and Petitioner filed a reply on October 5,

2022. Resp. Response; Pet. Reply.

This matter is now ripe for adjudication.

4

If Mr. Smilo’s symptoms of myasthenia gravis preceded vaccination, then Petitioner agrees that

the case involves a significant aggravation claim. Pet. Mot. at 8. If, however, onset occurred

after vaccination, Petitioner confirms that she is pursuing a “new injury claim,” or causation-in-

fact. Id.

3

IV. MEDICAL TERMINOLOGY

Myasthenia gravis is a rare disease, but “the most common disorder of the neuromuscular

junction.” Resp. Ex. E, Tab 1 at 1. 5 It is “a chronic autoimmune neuromuscular disease that

causes weakness in the skeletal muscles, which are responsible for breathing and moving parts of

the body, including the arms and legs.” Pet. Ex. 12 at 1. 6 The “hallmark” of the illness is

“muscle weakness that worsens after periods of activity and improves after periods of rest.” Id.

“Certain muscles such as those that control eye and eyelid movement, facial expression,

chewing, talking, and swallowing are often . . . involved in the disorder.” Id. Generally, the

initial symptom is “weakness of the eye muscles,” which manifests as “drooping of one or both

eyelids (ptosis).” Id. at 2. Others may have difficulty swallowing. Id. The extent of muscular

weakness ranges from a localized type of weakness involving the eye muscles to a severe form

that affects the muscles responsible for breathing. Id. Since weakness is a vague and common

symptom of many illnesses, the diagnosis may be delayed in those who have a mild presentation

or when weakness is limited to “a few muscles.” Id. at 4.

“Most patients—roughly two-thirds—initially present with ocular symptoms: ptosis

and/or diplopia without pupillary abnormalities. Weakness of the eye muscles is often

asymmetrical and variable.” Resp. Ex. E, Tab 1 at 2. Of the patients who present with ocular

symptoms, many will develop more generalized disease. Id. at 5. Myasthenia gravis crisis is

likely to occur early in the disease process, and “usually within the first [three] years following

diagnosis.” Id. “Myasthenic crisis is a complication of myasthenia gravis characterized by

worsening of muscle weakness, resulting in respiratory failure that requires intubation and

mechanical ventilation.” Resp. Ex. E, Tab 2 at 1. 7 Approximately 15-20% of patients who have

myasthenia gravis will experience a crisis at least once. Id. “The median time to first

myasthenic crisis from onset of [myasthenia gravis] ranges from 8-12 months. However,

myasthenic crisis may be the initial presentation [] in one-fifth of patients.” Id.

“Myasthenia gravis is caused by an error in the transmission of nerve impulses to

muscles. It occurs when normal communication between the nerve and muscle is interrupted at

the neuromuscular junction—the place where nerve cells connect with the muscles they control.”

Pet. Ex. 12 at 1. “[A]ntibodies (immune proteins) block, alter, or destroy the receptors for

acetylcholine at the neuromuscular junction, which prevents the muscle from contracting.” Id.

In most patients with the illness, this error in transmission “is caused by antibodies to the

acetylcholine receptor [(“AChR” or “AchR”)] itself.” Id.

5

Michael K. Hehir & Nicholas J. Silvestri, Generalized Myasthenia Gravis: Classification,

Clinical Presentation, Natural History, and Epidemiology, 36 Neurology Clinics 253 (2018).

6

Myasthenia Gravis Fact Sheet, Nat’l Inst. of Neurological Disorders & Stroke,

https://www.ninds.nih.gov/health-information/disorders/myasthenia-gravis (last modified July 6,

2018).

7

Linda C. Wendell & Joshua M. Levine, Myasthenic Crisis, 1 Neurohospitalist 16 (2011).

4

Treatment is aimed at improving muscle weakness. Pet. Ex. 12 at 4. Medications that

decrease the “breakdown of acetylcholine at the neuromuscular junction” are used to increase

muscle function. Id. at 4-5. Immunosuppressive drugs are given to “suppress[] the production of

abnormal antibodies.” Id. at 5. For severe symptoms, plasmapheresis and intravenous

immunoglobulin (“IVIG”) 8 can be given, but their effectiveness is limited in duration. Id.

V. FACTUAL SUMMARY

A. Summary of Relevant Facts 9

1. Pre-Vaccination Records

Mr. Smilo was born on May 31, 1953. Pet. Ex. 1 at 1. Prior to vaccination, he had a

history of hypertension, low back pain, and esophageal reflux. Pet. Ex. 3 at 1, 7; Pet. Ex. 6 at 12,

18.

In May 2016, Mr. Smilo was seen by his primary care physician, Dr. George Gavin, for

treatment of malaise, cough, nasal congestion, and fever. Pet. Ex. 3 at 23, 26. Dr. Gavin

diagnosed an upper respiratory infection. Id. at 26. Mr. Smilo saw Dr. Gavin again on August

22, 2016, complaining of dysphagia, 10 hoarseness, and cough. Id. at 18. Dr. Gavin ordered an

esophagogastroduodenoscopy (“EGD”). 11 Id. at 20.

Approximately one week later, on September 1, 2016, Mr. Smilo was seen by Dr. Jose

Mejia at Excela Health Medical Group for lower back pain. Pet. Ex. 3 at 14, 16. Mr. Smilo

reported “trouble with swallowing.” Id. at 14. Mr. Smilo returned to see Dr. Mejia on

September 26, 2016 for his lower back pain and reported “hoarseness and pain on swallowing.”

Id. at 10.

Mr. Smilo also saw his optometrist, Paul F. Ives, O.D., beginning in 2013 for eye

examinations and to monitor his ocular hypertension, pre-glaucoma condition. Pet. Ex. 45 at 16.

In 2015, Mr. Smilo was diagnosed with mild primary open angle glaucoma. Id. at 12.

8

IVIG is immune globulin used to treat various immunodeficiency disorders. Immune Globulin

Intravenous (Human), Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/

dorland/definition?id=78975 (last visited Apr. 24, 2023).

9

This summary contains only facts related to Mr. Smilo’s symptoms, onset, and diagnosis of

myasthenia gravis, as those are most pertinent. Additional factual summaries are set forth in the

parties’ expert reports and briefs. See, e.g., Pet. Mot. at 1-7; Resp. Response at 2-10.

10

Dysphagia means “difficulty in swallowing.” Dysphagia, Dorland’s Med. Dictionary Online,

https://www.dorlandsonline.com/dorland/definition?id=15265 (last visited Apr. 24, 2023).

11

EGD is the “endoscopic examination of the esophagus, stomach, and duodenum.”

Esophagogastroduodenoscopy, Dorland’s Med. Dictionary Online,

https://www.dorlandsonline.com/dorland/definition?id=17345 (last visited Apr. 24, 2023).

5

Thereafter, he saw Dr. Ives on a regular basis for glaucoma, through February 2017. See id. at 2-

12. His records do not contain any references either before or after vaccination to drooping

eyelids or ptosis.

2. Vaccination and Post-Vaccination Records

Mr. Smilo saw Dr. Gavin on October 17, 2016 for follow-up visit and reported that he

continued to have intermittent lower back pain. Pet. Ex. 3 at 1-8. Magnetic resonance imaging

(“MRI”) of the lumbar spine performed on October 11, 2016 showed degenerative and

postoperative changes of the lower back, with some impingement on the S1 nerve root. Id. at 4-

5. An EGD performed on September 28, 2016 showed chronic gastritis and esophagitis. Id. at

5-7. Physical examination revealed weakness of the right lower extremity and abnormal deep

tendon reflexes of the left lower extremity. Id. at 3. The flu vaccination at issue was

administered to Mr. Smilo at this visit. Id. at 7.

Approximately one month later, on November 17, 2016, Mr. Smilo returned to Dr.

Gavin’s office and was seen by Dr. Courtney Floyd. Pet. Ex. 4 at 27-29. Chief complaint was

“throat sore, eye drooping [one] week, slurred speech [one] week. Onset of symptoms was [one]

week[] ago. Patient report[ed] . . . tightness in throat.” Id. at 27 (emphasis omitted). Dr. Floyd’s

records also documented that Mr. Smilo had “right eye droop [three] months.” Id. (emphasis

omitted). Dr. Floyd documented that Mr. Smilo reported that at the “[e]nd [of] September after

endoscopy noticed he felt like he had something in this throat he couldn’t swallow[,] slurred

speech just started last night[,] eyelid drooping has been more chronic.” Id. Physical

examination revealed “right eyelid drooping.” Id. at 28. Dr. Floyd assessed Mr. Smilo with

“stroke-like symptoms,” and referred him to Dr. Roger Goebel at the emergency department

(“ED”) at Latrobe Hospital for further diagnosis and treatment. Id. In addition to a possible

stroke, Dr. Floyd also questioned whether Mr. Smilo had “myasthenia or [B]ell’s palsy.” Id. As

part of her plan, she wrote that if Mr. Smilo was “cleared from stroke [symptoms], can return for

workup of the eyelid.” Id.

Mr. Smilo presented to the ED that day, on November 17, 2016, and was initially seen by

the triage nurse, James Jellison, Registered Nurse (“RN”). Pet. Ex. 5a at 40. Nurse Jellison

wrote that Mr. Smilo complained of

slurre[d] speech and right sided eye droop. [Patient] state[d] he has been having

problems with his right eye for months, but had some difficulty with speech for

the last week . . . . [Patient] state[d] has had problems feeling like he had a

phlegm ball in the back of his throat[,] so he had an EGD at the end of September,

state[d] that he has been having worsening problems just this week however.

Id. Mr. Smilo reported that the “onset time was [three] months ago. The symptoms came on

gradually. The symptoms [had] worsened since onset.” Id. at 43. Diagnostic studies were

ordered and initiated. Id. at 45-47.

Subsequently, Mr. Smilo was seen by Dr. Goebel. Pet. Ex. 5a at 54. Dr. Goebel took a

history of present illness, stating that “onset time was [three] week(s) prior to arrival. . . . The

6

symptoms came on gradually. The symptoms [had] worsened since onset.” Id. at 55. The

history also stated that “[three] months ago noticed [right] drooping eyelid, slurred speech last

week, and last night at dinner wife noted mouth drooping. He has also had trouble swallowing

since his endoscopy in September.” Id. (emphasis omitted).

Diagnostic computerized tomography (“CT”) scan relative to the liver showed

“[q]uestionable areas of more focal decreased density . . . in the hepatic dome near the caudate

and right hepatic lobe . . . . The caudate lesion may exhibit mild mass effect and measures up to

5.5 cm.” Pet. Ex. 5a at 60. Radiologist Dr. Neal Klitsch’s impression was that the liver findings

could represent fatty infiltration, “but focal hepatic lesions [were] not excluded particularly in the

caudate. Follow-up contrast MRI of the liver [was] recommended.” Id. It does not appear that

follow-up MRI was done.

After diagnostic testing, Mr. Smilo was discharged home with instructions to follow up

with Dr. Gavin. Pet. Ex. 5a at 53. Discharged diagnosis was right mild ptosis, hoarse voice, and

dysphagia. Id. at 63. Mr. Smilo saw Dr. Gavin on December 7, 2016 and reported that “[h]is

dysphagia and voice disturbance ha[d] worsened,” but that “[h]is ptosis [was] not as bad as he

[was] no longer taping up his right upper lid.” Pet. Ex. 4 at 22. Mr. Smilo also reported a weight

loss of 30 pounds over the past three months. Id. “He ha[d] developed dysphagia for solids and

liquids.” Id. Physical examination revealed that Mr. Smilo had “a bulbar voice.” Id. at 24.

“[M]ild right upper lid ptosis” was also noted. Id. Dr. Gavin ordered additional diagnostic

testing and a referral to neurology. Id.

Mr. Smilo saw neurologist Dr. Louis W. Catalano on December 12, 2016. Pet. Ex. 6 at

12. Dr. Catalano documented that Mr. Smilo “report[ed] onset of trouble swallowing in August

2016. . . . In November 2016[,] he had onset of difficulty with speech and increased difficulty

with swallowing. . . . His wife noted right eyelid drooping in the spring of 2016; worse

[November 2016] and he complained of his eyelid blocking vision.” Id. Neurological

examination revealed “[n]asal speech[,] [s]evere dysarthria/severe dysphagia[,] [m]yopathic

facies,” and “[b]ilateral ptosis, R[ight]>L[eft] with fatigue.” Id. at 13. Dr. Catalano’s impression

was “[m]yasthenia [g]ravis, ocular-bulbar, acute.” Id. at 14. Diagnostic bloodwork was ordered

and treatment with IVIG and Mestinon 12 was initiated. Id. The bloodwork showed elevated

levels of AChR antibodies. Id. at 15, 18.

On December 22, 2016, Mr. Smilo presented to the ED complaining of weakness to the

point that he was having “increased difficulty holding up his head and swallowing.” Pet. Ex. 5a

at 127. Petitioner also completed of “an increased cough the past day.” Id. He was seen by Dr.

Michael Zorch, whose history noted that Mr. Smilo complained of “generalized weakness that

began some time ago.” Id. at 137 (emphasis omitted). Recently, he had experienced “increasing

12

Mestinon, a trademark for pyridostigmine bromide, “acts by inhibiting destruction of

acetylcholine and so facilitating transmission of impulses across the neuromuscular junction;

used as a cholinergic in the symptomatic treatment of myasthenia gravis.” Mestinon, Dorland’s

Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=30704 (last

visited Apr. 24, 2023); Pyridostigmine Bromide, Dorland’s Med. Dictionary Online,

https://www.dorlandsonline.com/dorland/definition?id=42398 (last visited Apr. 24, 2023).

7

generalized weakness,” “difficulty swallowing food,” “difficulty breathing[,] which is

exacerbated with exertion,” and “deteriorating speech.” Id. After bloodwork revealed low

potassium, Dr. Zorch admitted Mr. Smilo for treatment of his hypokalemia and myasthenia

gravis with acute exacerbation. Id. at 139, 142.

Admitting history and physical examination by Dr. Melissa Stewart noted that Mr. Smilo

had issues swallowing, and that he had experienced a “choking episode.” Pet. Ex. 5a at 109.

Since his condition had worsened, Mr. Smilo had not been able to tolerate solids and had a

choking episode when trying to swallow on the day of admission. Id. Therefore, he was to be

kept NPO, or nothing by mouth. Id. at 111, 123. Gastroenterology was consulted for a

percutaneous endoscopic gastrostomy 13 (“PEG”) tube placement “for nutritional support.” Id. at

112.

During hospitalization Mr. Smilo was initially monitored in the intensive care unit

(“ICU”) due to his risk of respiratory decompensation and need for intubation. Pet. Ex. 5a at

113, 118. Intubation was not required, but he did require bilevel positive airway pressure

(“BiPaP”) due to his low oxygen saturation levels. Id. He was treated with IVIG and steroids,

and ultimately improved so that he could be transferred out of ICU to a medical floor bed. Id. at

125. His dysphagia, however, did not improve, and he had a PEG tube inserted on January 3,

2017, for treatment of his “progressive dysphagia. He failed swallow evaluation and modified

barium swallow and had aspiration and penetration.” 14 Id. at 113, 125. Mr. Smilo’s discharge

note dated January 11, 2017 stated, “Dysphagia. The patient had a PEG tube placed. This is all

secondary to his myasthenia gravis.” Id. at 125; see also id. at 112, 165, 172, 174, 224

(explaining how Petitioner’s myasthenia gravis led to his dysphagia, which required placement

of a PEG tube since Petitioner was not improving with only a feeding tube).

Consents for anesthesia and the EGD and PEG tube were signed by Mr. Smilo on January

3, 2017. Pet. Ex. 5a at 301-03. In the consents, the PEG tube procedure was described as

“[p]lacement of a feeding tube through the abdominal wall into the stomach . . . with endoscopic

guidance.” Id. at 302.

The operative report for his PEG tube insertion was dated January 3, 2017 and identified

Dr. Ted A. Matthews as the surgeon and Dr. Douglas Klions as the gastroenterologist for the

procedure. Pet. Ex. 5a at 271-74. The procedure performed was “[EGD] with placement of a

gastrostomy tube.” Id. at 273. Dr. James I. Sadler was the anesthesiologist, and the anesthesia

13

Gastrostomy is a “surgical creation of an artificial opening into the stomach.” Gastrostomy,

Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=

19901 (last visited Apr. 24, 2023).

14

Modified Barium Swallow Study performed December 29, 2016 was abnormal. Pet. Ex. 5a at

103-04. “Throughout the examination there was penetration of barium with undercoating of the

epiglottis. There was occasional aspiration . . . .” Id. at 103.

8

type was monitored anesthesia care (“MAC”), and midazolam, 15 lidocaine, 16 and propofol 17

were administered. Id. at 281. The operative note stated that “[a]fter adequate sedation,” an

endoscope was placed by Dr. Klions (gastroenterologist) and “positioned in the midportion” of

the stomach, “directed towards the anterior abdominal wall.” Id. at 274. “A polypectomy snare

was passed into the stomach by [Dr. Klions], [and] opened fully . . . .” Id. On the outside of the

abdominal wall, “[t]he overlying skin was anesthetized with lidocaine and 0.5 cm incision was

made at the [] site. The introducer needle with overlying catheter was passed through this

incision and into the stomach under visualization with the endoscope. The needle and catheter

were [] captured by the endoscopy snare.” Id. “The gastrostomy tube . . . was pulled [] into the

stomach until the 3 cm mark of the gastrostomy tube was noted at skin level and adequate

placement of the [] tube [was achieved]. The patient tolerated the procedure well and was taken

to post anesthesia care unit in good condition.” Id. “There were no intraoperative complications.

Dr. Matthews and Dr. Klions were present . . . for the entirety of the procedure.” Id. Anesthesia

postoperative note from Dr. Sadler documented that the patient had “[n]o [a]pparent

[c]omplications” of anesthesia. Id. at 284.

During his hospitalization, Mr. Smilo had a syncopal episode due to autonomic

dysreflexia, and collapsed after voiding. Pet. Ex. 5a at 125, 160. He was treated with

intravenous fluids. Id. at 125. On January 11, 2017, Mr. Smilo was discharged, and on January

13, he was admitted to Westmoreland Inpatient Rehabilitation. Id.; Pet. Ex. 7a at 7. From

January 13 to January 21, 2017, Mr. Smilo received “aggressive” physical therapy, occupational

therapy, and speech therapy. Pet. Ex. 7a at 7, 9. He began taking Imuran (azathioprine), an

immunosuppressant medication for treatment of his myasthenia gravis, daily during this time.

Id. at 308-09, 342. During rehabilitation, he “progressively improved,” and was stable on

discharge. Id. at 9.

Mr. Smilo saw Dr. Gavin and Dr. Catalano in January 2017. Pet. Ex. 4 at 10-12; Pet. Ex.

6 at 6-10. At these visits, Mr. Smilo’s condition was stable; however, he continued to have

difficulty swallowing. Pet. Ex. 4 at 10, 12; Pet. Ex. 6 at 6, 9. His PEG tube remained in place.

Pet. Ex. 4 at 10; Pet. Ex. 6 at 6, 9. Medical records from these visits listed PEG tube placement

under Mr. Smilo’s surgical history. Pet. Ex. 4 at 11; Pet. Ex. 6 at 7. He was still taking Imuran

(azathioprine). Pet. Ex. 4 at 11; Pet. Ex. 6 at 8.

15

Midazolam is “used as an antianxiety agent and muscle relaxant.” Midazolam, Dorland’s

Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=31529 (last

visited Apr. 24, 2023).

16

Lidocaine is “a drug having anesthetic, sedative, analgesic, anticonvulsant, and cardiac

depressant activities, used as a local anesthetic.” Lidocaine, Dorland’s Med. Dictionary Online,

https://www.dorlandsonline.com/dorland/definition?id=28237 (last visited Apr. 24, 2023).

17

Propofol is “a short-acting anesthetic and sedative used in induction and maintenance of

general anesthesia and also for sedation, as during diagnostic procedures or in patients in

intensive care units.” Propofol, Dorland’s Med. Dictionary Online,

https://www.dorlandsonline.com/dorland/definition?id=41263 (last visited Apr. 24, 2023).

9

On March 20, 2017, laboratory testing revealed abnormal liver enzyme levels (elevated

alkaline phosphatase, aspartate aminotransferase (“AST”), alanine transaminase (“ALT”)) and

elevated bilirubin levels. Pet. Ex. 3 at 87. Mr. Smilo was diagnosed with “[a]cute cholestatic

jaundice” by Dr. Gavin, who suspected the cause was Mr. Smilo’s medication azathioprine. Pet.

Ex. 4 at 1, 3. Dr. Gavin discontinued the medication and ordered additional lab work and

diagnostic testing. Id. at 3. Abdominal CT performed on March 28, 2017 showed a “large 8 cm

central hepatic mass with marked intrahepatic and extrahepatic biliary ductal dilation

[(“IHBDD”)]” and “minimal ascites.” Pet. Ex. 3 at 113-14 (emphasis omitted). The CT also

showed that Mr. Smilo’s PEG tube had dislodged, specifically the “balloon of the percutaneous

gastrostomy tube appear[ed] extraluminal to the stomach.” Id. at 114.

Mr. Smilo saw hepatobiliary surgical oncologist Dr. David Geller on April 3, 2017. Pet.

Ex. 8 at 1. Dr. Geller reviewed the CT scan and wrote that the PEG tube balloon “[was] outside

the stomach” and would “need to be replaced.” Id. Dr. Geller noted a 70 pound weight loss,

“scleral icterus[,][18] and deep jaundice.” 19 Id. The CT showed a “giant 8 cm central liver mass”

and “massive IHBDD.” Id. Dr. Geller’s diagnosis was “large central liver HCC with obstructive

jaundice.” Id. He opined that Mr. Smilo was “not [an] operative candidate,” and that

“[p]rognosis [was] guarded.” Id.

That day, Mr. Smilo was admitted to the University of Pittsburgh Medical Center for

“obstructive jaundice and PEG tube malfunction.” Pet. Ex. 16a at 6. An endoscopic retrograde

cholangiopancreatography (“ERCP”) 20 with stent placement and PEG tube replacement

procedures were anticipated. Id. On April 3, Mr. Smilo also saw oncologist Dr. Padma

Rajagopal, whose impression indicated, “[p]atient report[ed] developing [myasthenia gravis] in

the setting of a flu shot in October; however, we do not have full information about diagnosis.

Myasthenia gravis has also been reported in [one] case report in the literature as being associated

with HCC.” 21 Id. at 36, 38.

18

Scleral icterus is “a yellow discoloration of the sclerae from hyperbilirubinemia.” Scleral

Icterus, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?

id=81855 (last visited Apr. 24, 2023).

19

Jaundice, or icterus, is “a condition characterized by hyperbilirubinemia and deposition of bile

pigments in the skin, mucous membranes, and sclera, with resulting yellow appearance of the

patient.” Jaundice, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/

definition? id=26548 (last visited Apr. 24, 2023).

20

An ERCP is “a combination of retrograde and transhepatic cholangiography, done to

demonstrate all portions of the biliary tree; it is performed by cannulation of the bile duct and

pancreatic duct through the papilla of Vater using a flexible fiberoptic endoscope with retrograde

injection of a radiopaque medium.” Endoscopic Retrograde Cholangiopancreatography,

Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=

65009 (last visited Apr. 24, 2023).

21

It is not clear what case report Dr. Rajagopal was referencing, nor does it appear the case

report was filed.

10

Mr. Smilo underwent an ERCP with stent placement and PEG tube replacement on April

4, 2017 by Dr. Mordechai Rabinovitz (surgeon) and Dr. Rohit Das (gastroenterologist). Pet. Ex.

16a at 87; Pet. Ex. 16c at 523. The procedures were done under MAC and Dr. Tomas Drabek

was the primary anesthesiologist. Pet. Ex. 16a at 87; Pet. Ex. 16c at 524. Consent forms for the

procedures were signed by Mr. Smilo. Pet. Ex. 16a at 26-29.

The ERCP was performed and revealed “markedly dilated right and left intrahepatics.”

Pet. Ex. 16a at 88. Two stents were placed, in the right and left intrahepatics. Id. The operative

note for the PEG tube replacement stated that “[t]here was evidence of a gastrostomy with no G-

tube present in the gastric body.” Id. at 91. The surgeon “creat[ed] a new tract for G-tube

placement” at a different site in the stomach. Id. A “trocar needle was introduced through the

abdominal wall and into the stomach under direct endoscopic view,” and a G-tube was placed.

Id. “The old G-tube was removed[,] and a dressing placed at the site.” Id. at 92.

Overnight, after surgery, Mr. Smilo developed hypotension and was transferred to ICU.

Pet. Ex. 16a at 40. He had “hemoperitoneum and septic shock.” Id. at 41. CT of the abdomen

on April 5, 2017 showed a “[l]arge irregular hematoma in the epigastrium near new PEG tube,”

large liver mass, and hepatic lymphadenopathy, suggesting metastatic spread of the cancer. Id. at

119-20. On April 6, 2017, Mr. Smilo’s respiratory status deteriorated, and he was intubated. Id.

at 41, 44. He passed away that night at 10:18 pm. Id. at 46-47. The death certificate listed cause

of death as liver failure due to HCC. Id. at 46; Pet. Ex. 17 at 1. Other significant conditions

contributing to death included myasthenia gravis, septic shock, and multiple organ failure. Pet.

Ex. 16a at 46; Pet. Ex. 17 at 1.

3. Vaccine Adverse Event Reporting System (“VAERS”) Report

A VAERS report was completed by Dr. Gavin. Pet. Ex. 9 at 1. The report is not dated.

See id. The report included the date of vaccination as October 17, 2016; Mr. Smilo’s name,

address, and telephone; the name of Dr. Gavin’s medical practice and contact information; and

the vaccination type (flu), manufacturer, lot number, and route and site of administration. Id.

The form stated that Mr. Smilo had received six prior doses of the flu vaccination (based on Dr.

Gavin’s medical records). Id. Dr. Gavin included a description of the adverse event: “[Mr.

Smilo] had drooping eyelids, occasional blurred vision, trouble swallowing, slurred speech, all

over body was tired, [and] trouble breathing.” Id. The adverse event onset date was indicated as

October 23, 2016. Id. The form also noted that the adverse event was “[l]ife threatening,” and

“[r]equired emergency room[] visit” and “[r]esulted in prolong[ed] [] hospitalization.” Id.

In addition to the report completed by Dr. Gavin, Petitioner also filed a copy of the report

obtained from the National Vaccine Information Center. Pet. Ex. 33. The report stated onset

was October 23, 2016, six days after vaccination. Id. at 1. The date of submission was not

noted; however, the data was entered on January 27, 2017. Id. The symptoms described were

identical to those in the above report, including “drooping eyelids, occasional blurred vision,

trouble swallowing, slurred speech, all over body was tired[,] [and] [t]rouble breathing.” Id. at 2.

11

B. Affidavits

1. Affidavit of Petitioner

Mrs. Smilo is the widow of Mr. Smilo and the Petitioner. Pet. Ex. 61 at 1. She executed

her affidavit on August 9, 2021. Id. at 2. Petitioner averred that prior to Mr. Smilo’s vaccination

on October 17, 2016, Mr. Smilo was in good health. Id. at 1. Approximately three weeks after

he received the flu vaccination, Mr. Smilo had “tightness in his throat, slurred speech, right

eyelid droop, and right sided mouth droop.” Id. Petitioner stated that Mr. Smilo did not have

these problems prior to vaccination. Id. She explained that Mr. Smilo was diagnosed with

myasthenia gravis, his symptoms progressed rapidly, and he passed away on April 6, 2017. Id.

Regarding the records of Dr. Catalano, which stated that Petitioner reported that Mr.

Smilo’s “right eyelid droop began and/or otherwise was present as early as the spring of 2016, or

approximately six [] months prior to his [flu] vaccination,” Petitioner explained “[she] do[es] not

recall making any such representation to Dr. Catalano or any other medical provider.” Pet. Ex.

61 at 2. She further averred that any reference in the medical record stating that the onset of Mr.

Smilo’s right eye ptosis occurred before vaccination is an “error and/or product of

miscommunication.” Id.

2. Affidavit of Dr. Gavin

Dr. Gavin executed his affidavit on August 13, 2021. Pet. Ex. 62 at 3. He stated that he

was Mr. Smilo’s primary care physician for five years before his death. Id. at 1. Prior to his flu

vaccination on October 17, 2016, Dr. Gavin averred that Mr. Smilo did not “complain of

fatigue/muscle weakness, slurred speech, blurred vision, mouth droop, and/or eyelid droop.” Id.

One month after Mr. Smilo received his flu vaccination, he was seen by Dr. Floyd in the

office on November 17, 2016. Pet. Ex. 62 at 1-2. Dr. Gavin noted Dr. Floyd “[was] no longer

with [the] practice group.” Id. at 2. Dr. Gavin provided a summary of the record from this office

visit in his affidavit. Id. Included in this part of the affidavit is a quote from Dr. Floyd’s note

stating, “right eye droop [three] months.” Id. (emphasis omitted).

Based on the content of the affidavit, it does not appear that Dr. Gavin saw Mr. Smilo

when he presented to the office on November 17, 2016. See Pet. Ex. 62 at 2. Dr. Gavin

reiterated, however, that Mr. Smilo had no prior complains of dysphagia or trouble swallowing.

Id. at 2. Based on his review of Dr. Floyd’s medical record, as well as his review of his own

prior records, Dr. Gavin opined that Mr. Smilo’s “onset of [] tightness in throat, eye drooping,

slurred speech, and right side mouth droop was within one [] week or one []day[] of his

November 17, 2016 office visit.” Id. He further opined that Dr. Floyd’s “medical entry of

‘droopy eye for [three] months’ is erroneous.” Id. at 3.

In Dr. Gavin’s August 22, 2016 record, he noted Mr. Smilo recently saw Dr. Ives, his

optometrist, and “Mr. Smilo made no mention that the optometrist found ptosis of his eye nor did

[Dr. Gavin] observe any ptosis.” Pet. Ex. 62 at 2. Dr. Gavin also reviewed the records of Dr.

12

Mejia, another physician in the practice, and according to Dr. Gavin, there was no reference to

ptosis in those records. Id.

C. Expert Reports

1. Petitioner’s Expert, Dr. George A. Small 22

a. Background and Qualifications

Dr. Small is a board-certified neurologist and neuromuscular specialist. Pet. Ex. 10 at 1;

Pet. Ex. 11 at 3. After obtaining his M.D. from Jefferson Medical School in Philadelphia,

Pennsylvania, he completed an internal medicine internship, neurology residency, and clinical

neuromuscular disease and electromyography (“EMG”) fellowship. Pet. Ex. 11 at 1. Over the

course of his career, he has held various teaching and hospital positions as well as membership

and appointments to professional societies and committees, and has authored or co-authored over

40 publications. Id. at 2, 4-9. Dr. Small is also “a board member of the Myasthenia Gravis

Association of Western Pennsylvania and ha[s] extensive experience in the diagnosis and

management of patients with [m]yasthenia [g]ravis.” Pet. Ex. 10 at 1.

b. Opinion

Dr. Small opined that the mechanisms that would explain the development of myasthenia

gravis were “an autoimmune reaction to the vaccine by means of molecular mimicry, bystander

activation, or polyclonal activation.” Pet. Ex. 10 at 4. Of these, he believed that molecular

mimicry was “the most probable theory as to why Mr. Smilo developed myasthenia gravis . . . as

a consequence of his [flu] vaccine.” Pet. Ex. 46 at 2. Although Dr. Small believed that Mr.

Smilo did not develop myasthenia gravis until after vaccination, if Mr. Smilo did have

myasthenia gravis at the time of his flu vaccination, then “within a reasonable degree of medical

and scientific certainty,” Mr. Smilo’s myasthenia gravis was “significantly aggravated” due to

his vaccination “by reason of the same pathologic autoimmune processes.” Pet. Ex. 10 at 6.

i. Loving Factor Four/Althen Prong One

According to Dr. Small, molecular mimicry is “[t]he most common mechanism by which

infections or vaccines induce autoimmunity.” Pet. Ex. 10 at 4 (quoting Pet. Ex. 13 at 2). 23

Molecular mimicry is the process whereby an infection or vaccine “incorporates an epitope that

is structurally similar to a self-antigen and therefore induces self-reactivity.” Id. (quoting Pet.

Ex. 13 at 2).

22

Petitioner submitted two expert reports from Dr. Small. Pet. Exs. 10, 46.

23

Nancy Agmon-Levin et al., Influenza Vaccine and Autoimmunity, 11 Isr. Med. Ass’n J. 183

(2009).

13

In support of the theory of molecular mimicry, Dr. Small cited an article by

Wucherpfennig 24 that described the mechanisms by which infectious agents cause autoimmune

illnesses. Pet. Ex. 43. Wucherpfennig defined molecular mimicry as the mechanism whereby

“[p]eptides from microbial proteins that have sufficient structural similarity with self-peptides

can activate autoreactive T cells.” Id. at 1. Wucherpfennig provided examples of molecular

mimicry, including experimental autoimmune encephalitis (“EAE”), where a peptide sequence

from a hepatitis B virus was identical to six amino acids of myelin basic protein in rabbits. Id. at

2. Wucherpfennig, however, did not discuss vaccines or myasthenia gravis.

Dr. Small agreed with Petitioner’s other expert, Dr. DeAngelo, whose opinions are

discussed below, that molecular mimicry was the most likely theory to explain Mr. Smilo’s

development of myasthenia gravis after vaccination. Pet. Ex. 46 at 2. Dr. Small opined that the

flu vaccination initiated

a complex interaction of T cells which reacted to the presence of the exogenously

administered [flu] proteins, caused production of antibodies that both would

attack the [flu] virus itself and also cause an apparent formation of [AChR]

antibodies, which are the specific proteins response for decreasing the ability of

motor nerves to activate muscles, thereby causing muscle weakness and

dysfunction.

Id. “[T]he antibodies produced in response to the vaccine antigen mistakenly bind to the

postsynaptic region and impair the function of the [AChR]. Simply put, with fewer receptor sites

available, the muscles receive fewer nerve signals, resulting in weakness and clinical

manifestation of the disease.” Pet. Ex. 10 at 4.

Dr. Small cited several articles specific to vaccines that he asserted demonstrate that “the

[flu] vaccine may trigger or exacerbate the symptoms of autoimmune neurological diseases such

as Guillain-Barre syndrome, [acute disseminated encephalomyelitis], transverse myelitis, and

systemic lupus erythematosus.” Pet. Ex. 10 at 3. The first of these, by Agmon-Levin et al., did

not discuss myasthenia gravis or any other neuromuscular autoimmune illness. See Pet. Ex. 13.

The authors discussed adjuvants, which are sometimes “added to vaccines to improve their

immunogenicity.” Id. at 2. There is no evidence here, however, that the flu vaccine given to Mr.

Smilo contained an adjuvant.

The next article cited by Dr. Small was from Domigo et al., 25 and in it, the authors

questioned whether the hepatitis B vaccine should be administered to those with myasthenia

24

Kai W. Wucherpfennig, Mechanisms for the Induction of Autoimmunity by Infectious Agents,

108 J. Clinical Investigation 1097 (2001). Petitioner’s other expert, Dr. DeAngelo, also

discussed this article. See Pet. Ex. 18 at 6-8, 14.

25

Valérie Domigo et al., Should Hepatitis B Vaccine Be Contra-indicated in Myasthenia

Gravis?, 29 Autoimmunity 139 (1998). Dr. DeAngelo also cited this article. Pet. Ex. 69.

14

gravis. 26 Pet. Ex. 14 at 1. The authors provided case reports on two patients. Id. The first

patient had no prior history of symptoms and developed neuromuscular symptoms one week

after a plasma-derived hepatitis B vaccine. Id. The second patient had a prior diagnosis of

myasthenia gravis, and her condition worsened in the month following her second injection of

the hepatitis B vaccine. Id. These cases did not involve the flu vaccine.

The last article cited by Dr. Small, from Sanghani et al., 27 reported a study utilizing

VAERS data about post-vaccination cases of myasthenia gravis. Pet. Ex. 15. Unfortunately,

only the abstract was filed, and therefore, the information was limited. See id. The authors

reviewed 71 reports of adult cases of myasthenia gravis from 1990 to 2017. Id. at 2. Of these,

73.6% were “newly diagnosed,” with an onset within six weeks of vaccination in the majority of

cases (77%). Id. The two most reported preceding vaccines were flu (26 cases or 36%) and

hepatitis B (17 cases or 24%). Id. The authors concluded that their “results suggest that the

reporting rate of post vaccination [myasthenia gravis] overlaps with its incidence in the general

population.” Id. The authors also postulated that because most cases occurred within six weeks

of vaccination, “some [] could be triggered by vaccination.” Id. The undersigned finds these

conclusions confusing because the authors stated that the incidence of myasthenia gravis after

vaccination is the same as that in the background population, suggesting that there is no

increased incidence attributable to vaccination. See id. However, the authors also suggested that

the temporal association between vaccination and onset of myasthenia gravis suggests a potential

causal association. See id. Without complete data, the information in this abstract and the

authors’ conclusions are difficult to understand.

ii. Loving Factor Five/Althen Prong Two

Dr. Small opined that “to [a] reasonable degree of medical and scientific certainty[,] []

the [flu] vaccination Mr. Smilo received on October 17, 2016 did cause his myasthenia gravis

disease.” Pet. Ex. 10 at 4. He opined that Mr. Smilo experienced an autoimmune illness, and

that literature and studies have associated myasthenia gravis with vaccines, including the flu

vaccination. Id. at 4-5.

Prior to vaccination, Dr. Small explained that Mr. Smilo was “relatively healthy.” Pet.

Ex. 10 at 5. Diagnostic studies were done, and there was no other cause found for Mr. Smilo’s

myasthenia gravis. Id. Further, Dr. Small averred that there was no other “explainable antigen”

except vaccination. Id. Additionally, Dr. Smilo noted that “Mr. Smilo’s primary care physician,

Dr. Gavin, filed a VAERS report noting the post-[flu] vaccine myasthenia gravis sequela.” Id.

Further, Dr. Small opined that myasthenia gravis and its resulting complications

significantly contributed to Mr. Smilo’s death. Pet. Ex. 10 at 5-6. Due to difficulty swallowing,

26

Of note, the article was published in 1998, and therefore, it may not reflect the most current

information.

27

Nirav Sanghani et al., Myasthenia Gravis After Vaccination in Adults the United States: A

Report from the CDC/FDA Vaccine Adverse Event Reporting System (1990-2017), 90

Neurology 6.437 (2018). Dr. DeAngelo also cited to this abstract. Pet. Exs. 60, 73.

15

Mr. Smilo was unable to eat, causing a weight loss of 70 pounds and requiring a PEG tube. Id. at

5. According to Dr. Small, this led to a “very weakened and debilitated general state” and made

him more vulnerable to “co-existent disease.” Id. at 6. Due to his myasthenia gravis, Mr. Smilo

experienced a “rapid and pronounced decline in his overall health,” which was “a significant

contributing factor in bringing about his death.” Id.

In summary, Dr. Small believed that “Mr. Smilo had a vaccine-induced autoimmune

event resulting in the onset of his myasthenia gravis.” Pet. Ex. 10 at 5. “[I]n the absence of

other possible infectious and noninfectious etiologies, of which none was identified in his work-

up and examination, the diagnosis of post-vaccination myasthenia gravis is most probable.” Id.

Moreover, Dr. Small opined that Mr. Smilo’s myasthenia gravis was a significant factor in his

death. Id. at 5-6.

iii. Loving Factor Six/Althen Prong Three

Regarding onset, Dr. Small opined that Mr. Smilo developed symptoms of myasthenia

gravis approximately three weeks after vaccination. Pet. Ex. 10 at 4-5. He explained that a

three-week interval between vaccination and onset was an appropriate time frame within which

the immune-mediated mechanism could occur, resulting in the autoimmune manifestations

consistent with myasthenia gravis. Id.

While Dr. Small acknowledged that there were references in the medical records about

Mr. Smilo having an eye droop that predated his flu vaccination, Dr. Small noted that Mr. Smilo

was not diagnosed with myasthenia gravis prior to vaccination. Pet. Ex. 10 at 6. Further, Dr.

Small asserted that Mr. Smilo did not have “any other symptoms of myasthenia gravis such as

dysphagia, dysarthria, muscle weakness, or respiratory distress.” Id. Dr. Small surmised that the

“eye droop could have resulted from an unrelated muscle deficiency specific to that eye muscle

as opposed to a larger neuromuscular disease process.” Id.

In support of his opinion that Mr. Smilo did not have ptosis prior to vaccination, Dr.

Small referred to the optometry records of Dr. Ives dated October 19, 2016, which did not

document that Mr. Smilo had ptosis. Pet. Ex. 46 at 1. Dr. Ives’ records documented that Mr.

Smilo had cataracts and glaucoma, which suggested to Dr. Small that if ptosis had been present

before the date of vaccination, Dr. Ives would have documented it. Id. at 1-2. Thus, Dr. Small

opined that “it is reasonable to conclude” that Mr. Smilo did not have ptosis at the time of the

visit, or prior to vaccination on October 17, 2016. Id. at 2.

As for Mr. Smilo’s symptom of difficulty swallowing, Dr. Small attributed it to his

esophageal reflux that was present prior to vaccination. Pet. Ex. 46 at 2. Dr. Small also

observed that Mr. Smilo’s records did not document that he had ptosis or difficulty swallowing

on the date that he received his vaccination, October 17, 2016. Id. Dr. Small asserted that this

fact further supports his opinion that Mr. Smilo did not have myasthenia gravis on the date of

vaccination. Id.

Although Dr. Small did not believe that Mr. Smilo had myasthenia gravis at the time of

vaccination, he opined that if Mr. Smilo did have myasthenia gravis, then “within a reasonable

16

degree of medical and scientific certainty[,] [Mr. Smilo’s myasthenia gravis] was significantly

aggravated as a result of said vaccination by reason of the same pathologic autoimmune

processes.” Pet. Ex. 10 at 6.

2. Petitioner’s Expert, Dr. James N. DeAngelo 28

a. Background and Qualifications

Dr. DeAngelo is a board-certified allergist and immunologist. Pet. Ex. 18 at 2; Pet. Ex.

44 at 2. He obtained his D.O. from the Philadelphia College of Osteopathic Medicine, after

which he completed an internship in family medicine, a residency in internal medicine, and a

fellowship in allergy and immunology. Pet. Ex. 44 at 1. For over 20 years, he has worked at

Allergy and Clinical Immunology Associates. Pet. Ex. 18 at 2. He is also active in teaching and

clinical research. Id.; Pet. Ex. 44 at 3-17.

b. Opinion

Dr. Angelo opined that “within a reasonable degree of medical and scientific

probability,” Mr. Smilo suffered “myasthenia gravis [] from the [flu] vaccine” that he received

on October 17, 2016. Pet. Ex. 18 at 1. He also believed that because Mr. Smilo developed

myasthenia gravis as a result of vaccination, he “required immunosuppressive treatment with

azathioprine,” and this medication caused his death from HCC. Id.

i. Loving Factor Four/Althen Prong One

The mechanism of causation proposed by Dr. DeAngelo is an “immune-mediated

haptenation[29] theory; that is, the process by which a foreign small-molecule hapten conjugated

to a self-protein creates a ‘neo-antigen,’ capable of inducing autoimmunity” via molecular

mimicry and/or bystander activation. Pet. Ex. 63 at 1, 3-4. Over his four reports, Dr. DeAngelo

refined his theory in the context of post-vaccination myasthenia gravis. He started with general

principles of molecular mimicry, and then developed his theory of haptenization. Dr. DeAngelo

also referenced additional concepts or mechanisms, including neo-antigens, bystander activation,

superantigens, and polyclonal activation. Additionally, he provided medical literature and case

reports.

1. Molecular Mimicry

In his first report, Dr. DeAngelo described molecular mimicry as the process by which

“inflammation from viral antigens in the vaccine results in local activation of antigen-presenting

cells that, in turn, results in enhanced processing and presentation of self-antigens.” Pet. Ex. 18

at 6. He asserted that molecular mimicry is “the most widely accepted hypothesis as to how viral

vaccine antigens produce and maintain autoimmune responses.” Id. at 7. As an example, Dr.

28

Petitioner submitted four expert reports from Dr. DeAngelo. Pet. Exs. 18, 47, 55, 63.

29

Dr. DeAngelo also referred to this as “haptenization.” See Pet. Ex. 63 at 2.

17

DeAngelo explained how Streptococcus pyogenes, the bacteria that causes strep throat, can cause

autoimmune complications including rheumatic fever and glomerulonephritis. Id. at 8-9.

According to Dr. DeAngelo, molecular mimicry is either T-cell dependent or T-cell

independent. Pet. Ex. 18 at 7. In the T-cell mediated form, “autoreactive T cells are activated by

peptides” with “structural similarity to self-peptides,” and these reactive T cells (lymphocytes)

“recognize fragmentized microbial peptide antigens presented by major histocompatibility

complex (MHC) I or II glycoprotein molecules on antigen-presenting cells.” Id. Autoreactive

antibodies are generated and attach to the cell surface of a “antigenically similar peptide

sequence” or “attach directly to cross-reactive self-antigens, initiating a cascade of autoimmune

damage to the host tissue.” Id. at 8.

After vaccination, the “immune system [] produce[s] antibodies that recognize and bind

to viral hemagglutinin (HA) and neuraminidase (NA) surface proteins. Antibody and T-cell

binding to these antigenic sites is necessary for antibodies [to] neutraliz[e] [] the virus and []

prevent[] or mitigate[e] [] the illness.” Pet. Ex. 47 at 3. Dr. DeAngelo explained that the flu

virus mutates every year, resulting in “variations in these surface antigen proteins, and less

commonly, in major antigenic shifts from one HA or NA to another.” Id. These changes require

the flu vaccine to be changed every year to “antigenically match” the “antigenic character” of the

virus. Id. Dr. DeAngelo opined that “these surface proteins are the cause of Mr. Smilo’s

idiosyncratic autoimmune reaction to the [flu] vaccine.” Id. He attributed this “antigenic

variability” in the flu vaccine from year to year as the reason that studies have not found “a

convincing relationship between [the] [flu] vaccination” and myasthenia gravis. 30 Id.

Regardless, he opined that “it is undoubtedly possible that a similarly rare and challenging to

prove association exists between the [flu] vaccine and Mr. Smilo’s [myasthenia gravis].” Id. at

4.

Specific to myasthenia gravis, although not in the context of vaccination, Dr. DeAngelo

cited research by Schwimmbeck et al. 31 to support the mechanism of molecular mimicry as

playing a causal role in myasthenia gravis. Pet. Ex. 36. Schwimmbeck et al. reported a

homologous protein sequence shown to cross-react between an AChR epitope and a herpes

simplex virus glycoprotein. Id. at 1. The authors suggested that the herpes simplex virus may be

associated with some cases of myasthenia gravis. Id.

30

For support, Dr. DeAngelo cited to an article authored by Zinman et al., cited by Respondent’s

expert, Dr. Lancaster, and discussed below, which did not find any association between the flu

vaccination and myasthenia gravis. Pet. Ex. 47 at 3 (citing Resp. Ex. A, Tab 4 (Lorne Zinman et

al., Safety of Influenza Vaccination in Patients with Myasthenia Gravis: A Population-Based

Study, 40 Muscle & Nerve 947 (2009)).

31

P L Schwimmbeck et al., Molecular Mimicry and Myasthenia Gravis: An Autoantigenic Site

of the Acetylcholine Receptor Alpha-Subunit That Has Biologic Activity and Reacts

Immunochemically with Herpes Simplex Virus, 84 J. Clinical Investigation 1174 (1989).

18

Dr. DeAngelo also cited a paper by Stübgen. 32 Pet. Ex. 39. Stübgen examined the

relationship between the hepatitis B vaccination and myasthenia gravis, and reported that “onset

or exacerbation of myasthenia gravis [] was very rarely associated with the [hepatitis B]

vaccine.” Id. at 3. Further, Stübgen opined that hepatitis B causation “appeared temporal only; a

molecular mimicry relationship seemed unlikely” because the potential mimics were

“structurally unrelated.” Id. While Stübgen suggested it was “conceivabl[e]” that the hepatitis B

vaccine provoked myasthenia gravis, Stübgen did not opine that vaccine causation was likely.

Id.

The next paper cited by Dr. DeAngelo in support of molecular mimicry was from He et

33

al., where mice injected with a live-attenuated Japanese encephalitis vaccine developed

significant antibodies and some features of myasthenia gravis. Pet. Ex. 26 at 3-4, 8. The mice

were also given other vaccines, including hepatitis B, diphtheria-tetanus-pertussis, measles-

mumps-rubella, and Bacillus Calmette-Guérin (“BCG”), however, these vaccinations did not

induce muscular weakness characteristic of myasthenia gravis. Id. at 3, 7 fig.2, 8, 13.

Lastly, Dr. DeAngelo cited Im et al., 34 who reported on a study where rats were injected

with Haemophilus influenzae 35 with a “mimicry peptide” that was “50% homologous” to a T-cell

epitope of AChR α subunit. Pet. Ex. 29 at 6. Interestingly, instead of inducing disease, the result

was “protection against subsequent induction of [experimental autoimmune myasthenia gravis],”

demonstrating that “a microbial-derived peptide can modulate the antibody-mediated auto-

immune response in [experimental autoimmune myasthenia gravis].” Id. at 7. The authors

suggested that “in some cases[,] cross-reactive microbial proteins and peptides derived from

viruses or bacteria can work as protective immunomodulators in regulation of T-cell-mediated

autoimmune disease.” Id. at 6.

32

Joerg-Patrick Stübgen, Neuromuscular Disorders Associated with Hepatitis B Vaccination,

292 J. Neurological Scis. 1 (2010).

33

Dan He et al., Molecular and Clinical Relationship Between Live-Attenuated Japanese

Encephalitis Vaccination and Childhood Onset Myasthenia Gravis, 84 Annals Neurology 386

(2018).

34

Sin-Hyoeg Im et al., Protective Molecular Mimicry in Experimental Myasthenia Gravis, 126 J.

Neuroimmunology 99 (2002).

35

Haemophilus influenzae is “a species once thought to be the cause of epidemic [flu].”

Haemophilus Influenzae, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/

dorland/definition?id=79896 (last visited Apr. 24, 2023).

19

Dr. DeAngelo conceded that Tackenberg et al. 36 did not find that the flu vaccine caused

or exacerbated myasthenia gravis; however, he attributed the outcome to the small study size.

Pet. Ex. 18 at 12 (citing Pet. Ex. 40 at 1). The study included 62 patients with myasthenia gravis

(with known antibodies against AChR), randomized to receive either the seasonal flu vaccine (31

patients) or a placebo (31 patients). Pet. Ex. 1-2. Baseline AChR antibody titers were compared

to values at three and 121 weeks post-vaccination. Id. at 2. There were no cases of “clinical

deterioration nor any serious or severe adverse events due to vaccination.” Id. at 3. Further,

there was no “clinically relevant increase of AChR-[antibody]-titer,” no increase in aggravation

of myasthenia gravis, and no increase in adverse events. Id. at 5.

2. Haptenization

In his second expert report, Dr. DeAngelo introduced the concept of haptenization. Pet.

Ex. 47 at 4. He stated that “[t]he introduction of any foreign material to the human body always

raises the possibility of haptenization.” Id. “According to the classic hapten theory, . . . the

immune reaction to molecularly small, normally non-antigenic compounds, known as haptens,

results from the hapten binding with a carrier protein from the patient to generate an autoimmune

response.” Id. at 4-5. “Haptenization is now a well-established mechanism whereby a non-

immunogenic drug or vaccine is rendered immunogenic via molecular mimicry.” Id. at 5.

In support of his haptenization/molecular mimicry mechanism, Dr. DeAngelo cited an

article by Bugelski. 37 Pet. Ex. 49. Bugelski explained that “[m]ost small-molecule drugs or

xenobiotics (that is, non-peptides with a molecular mass of ~300-600 Da) are not direct

immunogens.” Id. at 1. For there to be “immunogenicity,” there must be a “covalent

conjugation of the xenobiotic to a host protein.” Id. at 2. An example is penicillin, which can

trigger a severe immune reaction (anaphylactic reaction), probably through “the formation of [a]

drug-protein conjugate[].” Id. Bugelski explained that “[t]he formation of hapten-peptide

conjugates is [] the first step in the activation of the immune system.” Id. The hapten-peptide

conjugate is “carried to and displayed—in conjugation with major histocompatibility complex

(MHC) proteins, . . . also known as human lymphocyte antigen (HLA) proteins—on the surface

of antigen-presenting cells (APCs).” Id. The “[h]apten-peptide conjugates on the surface of

APCs interact with immature T and B lymphocytes through T- and B-cell receptors,

respectively.” Id. The immune system is then activated, and “governed by the antigen-binding

specificity of the T- and B-cell receptors.” Id. Thus, through the complex process described by

Bugelski, some hapten-peptide conjugates may play a role in activating the immune system. See

id. These immune-mediated adverse drug effects are “the result of complex interactions between

36

Björn Tackenberg et al., Acetylcholine Receptor Antibody Titers and Clinical Course After

Influenza Vaccination in Patients with Myasthenia Gravis: A Double-Blind Randomized

Controlled Trial (ProPATIent-Trial), 28 EBioMedicine 143 (2018). Dr. Lancaster also cited this

article. Resp. Ex. A, Tab 3.

37

Peter J. Bugelski, Genetic Aspects of Immune-Medicated Adverse Drug Effects, 4 Nature

Revs. 59 (2005).

20

drug-metabolizing enzymes, immune sensitization[,] and immune effectors,” along with “genetic

aspects of this interplay.” 38 Id. at 1.

Dr. DeAngelo took Bugelski’s explanation about how drug haptens are formed from non-

immunogenic molecules, and co-opted it to posit that the flu vaccine could produce “autoreactive

immunoglobulin G (IgG) [],[39] specific to the AChR.” Pet. Ex. 47 at 6 fig.1, 7 fig.2. In doing

so, Dr. DeAngelo altered two figures from Bugelski by changing words in the figures and in the

paragraphs describing the figures, and then reached conclusions that were not discussed by

Bugelski. Compare id., with Pet. Ex. 49 at 3 fig.1, 5 fig.2.

In summary, Bugelski discussed how xenobiotics, small molecules that do not cause an

immune response, can become linked to a protein, and through a complex process, and with the

interaction of metabolic enzymes, can ultimately cause an immune response. See Pet. Ex. 49 at

1-2. The concepts are taken out of context, and Dr. DeAngelo cited no precedent for their

application in the context of the facts and circumstances here. Further, Bugelski did not describe

how vaccines generally, or the flu vaccine specifically, could, through haptenization-induced

molecular mimicry, create an immune response that could lead to the development of myasthenia

gravis.

3. Neo-antigen and Hapten-Modified Cancer

Vaccines

In his fourth and final expert report, Dr. DeAngelo introduced the concept of a neo-

antigen as part of his hapten theory—“that is, the process by which a foreign small-molecule

hapten conjugated to a self-protein creates a ‘neo-antigen’ capable of inducing autoimmunity.”

Pet. Ex. 63 at 1. The concept of the neo-antigen is his response to Respondent’s expert’s, Dr.

Lancaster’s, criticism of his theory. Id. Dr. DeAngelo offered his hapten/molecular

mimicry/neo-antigen theory to explain how a “strong 3-dimensional molecular homology with

human skeletal muscle [AChR] can occur.” Id. According to Dr. DeAngelo, “[t]he process of

haptenation creates a neo-antigen . . . one that is new and not previously present.” Id. at 2. The

process of haptenation “is a well-recognized mechanism of autoimmune disease initiation and

breakdown of self-tolerance.” Id. Further, “haptenation of an endogenous self-protein contorts

the three-dimensional conformation for self-proteins, exposing previously hidden epitopes and

rendering them immunogenic.” Id. Dr. DeAngelo acknowledged that the “application of the

haptenation theory to induce or exacerbate autoimmunity is somewhat novel in the context of the

presentation of post-vaccine myasthenia gravis,” but argued that nonetheless, it is “sound and

reliable.” Id. at 1.

38

For the complete description of this process, see Pet. Ex. 49 at 2-4.

39

Immunoglobulins are “structurally related glycoproteins that function as antibodies.”

Immunoglobulin, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/

definition?id=24894 (last visited Apr. 24, 2023). For more information on IgG, see Peter J.

Delves, Acquired Immunity, Merck Manual, https://www.merckmanuals.com/home/immune-

disorders/biology-of-the-immune-system/acquired-immunity# (last updated Sept. 2022).

21

In support of these ideas, Dr. DeAngelo cited to Bolon, 40 who described the loss of self-

tolerance, and its role in the development of autoimmune disease:

Under normal conditions, the immune system exhibits tolerance (an inability to

react) to molecules recognized as “self,” and thus does not respond to elements

(whether carbohydrate, nucleic acid, or protein) that are expressed in endogenous

tissues. When self-tolerance is lost, the immune system is deployed against one

or more of the body’s own molecules.

Pet. Ex. 66 at 1. Bolon described “recent themes” relevant to “pathogenic mechanisms that lead

to the end of self-tolerance.” Id. One mechanism for the breakdown of self-tolerance was

“[s]elf-antigen alteration by attachment of a hapten (chemical or metal) to make a neo-antigen.”

Id. at 4 tbl.2.

Bolon further explained that the formation of a neo-antigen is a “primary means” of

autoimmune disease induction. Pet. Ex. 66 at 9.

The conjugation of a hapten—usually a reactive metal or small chemical—to an

endogenous molecule changes the self-epitope’s confirmation. Contortions in the

cross-linked molecule generally will expose new epitopes, when may be

recognized as new antigens. Alternatively, the conjugated endogenous molecule

may now have a much higher affinity for MHC II, which will process it to

reactivate anergic cells. Any resulting [autoimmune disease] stemming from

production of an immune response against a neo-antigen may persist after the

hapten is cleared, presumably because the reaction is manly against the

endogenous portion of the complex.

Id. (internal citations omitted). As described by Bolon, the conjugation of a hapten usually

involves a reactive metal or small chemical, not a vaccine, and not the flu vaccine. See id.

Dr. DeAngelo also referenced two articles by Berd related to the development of

anticancer vaccines, not vaccines used to prevent infectious illness, like the flu vaccine, in

support of his theory. See Pet. Ex. 64; 41 Pet. Ex. 65. 42 In the first, Berd discussed hapten-

modified tumor vaccines. Pet. Ex. 64 at 1. He began by describing the discovery of haptens,

“simple chemicals . . . incapable of inducing an immune response by themselves, but []

immunogenic when attached . . . to a protein carrier.” Id. Six haptens have been studied and

40

Brad Bolon, Cellular and Molecular Mechanisms of Autoimmune Disease, 40 Toxicologic

Pathology 216 (2012).

41

David Berd, Hapten-Modified Tumor Vaccines, in Handbook of Cancer Vaccines 275

(Michael A. Morse et al. eds., 2004).

42

David Berd et al., Immunopharmacologic Analysis of an Autologous, Hapten-Modified

Human Melanoma Vaccine, 22 J. Clinical Oncology 403 (2004).

22

used in research for their various immunological responses. Id. at 3 tbl.1. Berd explained that

hapten conjugation has been used to provide “new antigenic determinants” to “increase the

binding of T-cell receptors (TCRs) to self peptide enough for T-cell activation, and once

activated, the T cells could react with unmodified peptide.” Id. at 4. In more simple terms,

haptens can be used to modify “otherwise nonimmunogenic peptide[s]” to induce an immune

response. Id. For example, mice injected with “hapten-modified thyroglobulin developed

histological evidence of autoimmune thyroiditis.” Id. These concepts have been applied in the

context of immunotherapy for treatment of cancer (hapten immunology); hapten-modified

vaccines have been developed for animal experiments with the goal of treating aggressive

tumors. Id. at 5-7. “[H]apten modification can result in immune responses” that can be applied

to “tumor antigens” to delay or slow tumor growth. Id. at 19. Berd, however, did not discuss

how haptens could be relevant to the facts and circumstances here, or explain how a flu vaccine

could cause myasthenia gravis. The same is true for the second article by Berd et al., which also

described a hapten-modified human melanoma vaccine. See Pet. Ex. 65.

In summary, Dr. DeAngelo has suggested that hapten conjugation in the context of

vaccination can somehow be involved in the pathogenesis of myasthenia gravis, but the articles

cited do not explain how vaccines given to protect against viral infection, or the flu vaccine

specifically, can cause myasthenia gravis. See Pet. Ex. 63 at 1-3.

4. Bystander Activation

In addition to molecular mimicry, Dr. DeAngelo stated that “[o]nce autoimmunity is

initiated via hapten-generated molecular mimicry, downstream T-cell Th1, Th2, Th17, and B cell

effectors induce cytokine, cytotoxic cellular, and autoantibody responses to not only the hapten

and hapten-carrier complex but also previously tolerated self-peptides.” Pet. Ex. 63 at 3. This

downstream activity “can result in a generalized pro-inflammatory environment, whereby

‘bystander activation’ occurs.” Id. Dr. DeAngelo defined “bystander activation” as “the

nonspecific activation of previously quiescent immune cell lines.” Id.

Dr. DeAngelo suggested that bystander activation “is of particular interest,” assuming

Mr. Smilo had myasthenia gravis prior to vaccination. Pet. Ex. 63 at 3. In that scenario, Dr.

DeAngelo stated that “hapten-generated molecular mimicry [is] less critical” because “[AChR]

autoantibody generation may have already been underway.” Id. Regardless, he opined that

bystander activation “could increase autoantibody generation, enhance T-cell cytotoxicity,

amplify the existing inflammatory cytokine milieu, increase the upregulation of the immune

system, and thereby exacerbate [Mr. Smilo’s] underlying autoimmune disease and its resulting

symptomology.” Id.

23

5. Superantigens, Polyclonal Activation, and

Epitope Spreading

Other ideas offered by Dr. DeAngelo involve “superantigens” 43 and “polyclonal

activation.” Pet. Ex. 63 at 3. He stated that “under certain circumstances, where a superantigen

is generated by the hapten complex, polyclonal activation takes place.” Id. Citing Bolon, he

defined polyclonal activation as “the process whereby superantigen[s] drive[] nonspecific cross-

linking of MHC II to TCR on numerous T-cell lineages [that] results in them becoming primed

for myriad epitopes. Such epitopes are involved in the original hapten-mediated loss of

tolerance, but their unintended activation releases even more cytokines.” Id. (citing Pet. Ex. 66

at 3-4). Bolon, however, does not discuss superantigens or this mechanism. And Dr. DeAngelo

does not define superantigens or otherwise develop this mechanism.

Next, Dr. DeAngelo identified “polyclonal activation of memory B-cells” as a

“contributing immunologic driver” of Mr. Smilo’s myasthenia gravis. Pet. Ex. 18 at 14. He

cited Bernasconi et al., 44 who “show[ed] that human memory B lymphocytes proliferate and

differentiate into plasma cells in response to polyclonal stimuli, such as bystander T cell

help[ers].” Pet. Ex. 20 at 1. But Dr. DeAngelo did not explain how this process applies in the

context of alleged post-vaccination myasthenia gravis. See Pet. Ex. 18 at 6-7, 14. And the

authors of Bernasconi et al. did not discuss how polyclonal activation of memory B-cells could

cause an autoimmune disease due to vaccination, or how vaccination could serve as a

“continuing immunologic driver” of illness.

Dr. DeAngelo also suggested that “epitope spreading” may also be a “contributing

immunologic driver” of myasthenia gravis. Pet. Ex. 18 at 14. He cited two articles in support of

this idea. The first is by Lehmann et al. 45 and dealt with EAE, “a prototype of CD4+ T-cell

mediated autoimmune disease” and multiple sclerosis. Pet. Ex. 31 at 1. Dr. DeAngelo did not

define “epitope spreading” or explain why he referenced the article.

43

Superantigen is “any of a group of powerful antigens occurring in various bacteria and viruses

that binds outside of the normal T-cell receptor site and is able to react with multiple T-cell

receptor molecules of a given β-chain variable element, regardless of their α-chain sequence,

thus activating T cells nonspecifically. Included are staphylococcal enterotoxins and toxins

causing toxic shock syndrome and exfoliative dermatitis.” Superantigen, Dorland’s Med.

Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=48059 (last visited

Apr. 24, 2023).

44

Nadia L. Bernasconi et al., Maintenance of Serological Memory by Polyclonal Activation of

Human Memory B Cells, 298 Science 2199 (2002).

45

Paul V. Lehmann et al., Spreading of T-Cell Autoimmunity to Cryptic Determinants of an

Autoantigen, 358 Nature 155 (1992).

24

The second article is by Smatti et al. 46 and discussed the potential of viruses to modify

autoimmune illnesses like diabetes, systemic lupus erythematosus, and others. Pet. Ex. 38 at 1.

In the article, “epitope spreading” is defined as the mechanism by which “a viral infection

triggers the release of more self-antigens and the de novo activation of autoreactive cells, which

consequently spread to target additional self-epitopes.” Id. at 2. The authors stated that

molecular mimicry and bystander activation have been associated with EAE and multiple

sclerosis, West Nile virus-mediated myasthenia gravis, and other illnesses, and provided a

review of potential mechanisms of causation, including molecular mimicry, bystander activation,

and epitope spreading. Id. at 1-2, 2 fig.1. In the “[e]pitope spreading model,” the process begins

with “[p]ersistent viral infection,” which leads to sustained tissue damage and “release of new

self-antigens” and ultimately to autoimmunity. Id. at 2 fig.1. The authors discussed enteric

infections, Coxsackie B viruses, rotaviruses, the flu A virus, herpesviruses, and other viruses, as

well as the different mechanisms that trigger autoimmune illnesses. Id. at 2-10, 8-10 tbl.1.

Myasthenia gravis was identified as an autoimmune disease that has been associated with the

West Nile virus and molecular mimicry was identified as the proposed mechanism. Id. at 9 tbl.1.

The authors, however, did not discuss vaccines in association with myasthenia gravis, and it is

not clear why Dr. DeAngelo cited the article in reference to “epitope spreading.” See Pet. Ex. 18

at 14.

6. Case Reports and Data from VAERS 47

In addition to articles about his various theories, Dr. DeAngelo also referenced case

reports in support of his opinions about causation. Chung et al. 48 reported a case of myasthenia

gravis with onset three days after administration of the second human papillomavirus (“HPV”)

vaccination. Pet. Ex. 68 at 1. By week four, the patient’s symptoms had “completely resolved.”

Id. at 2. The authors did not reach any conclusions about this “possible causal relationship.” Id.

at 3.

Dr. DeAngelo, like Dr. Small, also cited to Domigo et al., who discussed two case reports

of myasthenia gravis after the hepatitis B vaccine. Pet. Ex. 14. As explained above, the first

patient did not have a history of myasthenia gravis, developed symptoms one week after receipt

of a plasma-derived hepatitis B vaccine, and stabilized with treatment. Id. at 1. The second

patient had pre-existing myasthenia gravis and her condition worsened after administration of the

plasma hepatitis B vaccine. Id. No causal theory was posited by the authors. See id. at 1-2.

46

Maria K. Smatti et al., Viruses and Autoimmunity: A Review on the Potential Interaction and

Molecular Mechanisms, 11 Viruses 1 (2019).

47

Dr. DeAngelo also cited a case involving a patient who received intravesical BCG for bladder

cancer and developed myasthenia gravis shortly thereafter. Pet. Ex. 75 at 1 (Tsubasa Takizawa

et al., New Onset of Myasthenia Gravis After Intravesical Bacillus Calmette-Guerin, 96

Medicine 1 (2017)). Symptoms resolved after treatment with steroids. Id.

48

Ji Yeon Chung et al., Myasthenia Gravis Following Human Papillomavirus Vaccination: A

Case Report, 18 BMC Neurology 1 (2018).

25

Two cases of myasthenia gravis following Covid-19 vaccines were also cited by Dr.

DeAngelo. The first, from Chavez and Pougnier, 49 was an 82-year-old who developed

intermittent periods of slurred speech with onset four weeks after receipt of the initial Covid-19

vaccine (and two days after the second dose, but symptoms had preceded the second dose). Pet.

Ex. 67 at 1. The patient had elevated AChR antibodies and EMG testing consistent with

myasthenia gravis, and had rapid disease progression. Id. at 1-2. The authors discussed the

mechanisms of molecular mimicry and bystander activation as related to the mRNA vaccine, 50

and suggested that bystander activation may be the more plausible of the two theories for their

patient, noting that “previously existing self-antigen [] released due to stimulation of the innate

immune system . . . [may] result[] in activation of auto-reactive T cells.” Id. at 2.

The second Covid-19 vaccine case report, authored by Lee et al., 51 described a 33-year-

old who had “generalized weakness and diplopia on the evening she received her second dose”

of the vaccine. Pet. Ex. 72 at 1. The patient did not have elevated AChR antibodies and her

EMG study was normal. Id. The authors stated that the “underlying pathogenesis [was]

unclear,” but they suggested that the “changes that take place in the immune response after

vaccination could elicit the production of antibodies against [AChR].” Id. at 1.

In addition to case reports, Dr. DeAngelo cited two abstracts of data from the Centers for

Disease Control and Prevention (“CDC”) and Food and Drug Administration (“FDA”),

summarizing reports of myasthenia gravis after vaccinations from VAERS from 1990 to 2017.

Pet. Ex. 15 (adult cases); 52 Pet. Ex. 58 (pediatric cases). 53 As previously noted above in Dr.

Small’s expert report section, 71 adult cases were reported. Pet. Ex. 15 at 2. Of the 71 cases, 57

were determined to be definite cases of myasthenia gravis. Id. The flu and hepatitis B vaccines

49

Augustine Chavez & Charlotte Pougnier, A Case of COVID-19 Vaccine Associated New

Diagnosis Myasthenia Gravis, 12 J. Primary Care & Cmty. Health 1 (2021).

50

There is no evidence here that the flu vaccine at issue was an mRNA vaccine. Messenger

RNA, or mRNA, are “RNA molecules . . . that serve as templates for protein synthesis

(translation); in eukaryotes they have characteristic posttranscriptional modifications, the 5’-cap

and poly A tail. The base sequence of an mRNA transcript completely specifies the

corresponding polypeptide amino acid sequence.” Messenger RNA, Dorland’s Med. Dictionary

Online, https://www.dorlandsonline.com/dorland/definition?id=104391 (last visited Apr. 24,

2023).

51

Myung Ah Lee et al., Early-Onset Myasthenia Gravis Following COVID-19 Vaccination, 37 J.

Korean Med. Sci. 1 (2022).

52

Both Dr. Small and Dr. DeAngelo cited this abstract. See Pet. Exs. 15, 73.

53

Rajanigandhi Hanumanthu et al., Pediatric Myasthenia Gravis After Vaccination in the United

States: A Report from the CDC/FDA Vaccine Adverse Event Reporting System (1990-2017), 90

Neurology 2.326 (2018).

26

were most often reported (26 and 17 respectively). Id. Because only an abstract was filed,

limited information was provided. The authors concluded that the rate of myasthenia gravis

reported was within the expected range based on the general population; however, they

recommended monitoring for myasthenia gravis after vaccination due to the temporal association

between vaccination and disease onset. Id. No causal mechanisms were discussed. See id.

ii. Loving Factor Five/Althen Prong Two

Dr. DeAngelo opined that “the [flu] vaccine was the most likely cause of Mr. Smilo’s

[myasthenia gravis].” Pet. Ex. 55 at 4. He stated “[t]here is the potential for the seasonal [flu]

vaccine to induce [myasthenia gravis] in the constitutionally predisposed individual via

haptenization-induced molecular mimicry.” Id.

He summarized that “Mr. Smilo received his [flu] vaccine on October 17, 2016, with his

symptoms of [myasthenia gravis] presenting or significantly worsening approximately three []

weeks post-vaccine.” Pet. Ex. 63 at 5. Further, Dr. DeAngelo noted that there was no other

“inciting causal infectious or noninfectious” cause for Mr. Smilo’s illness recorded in his

medical records. Id.

Lastly, Dr. DeAngelo observed that Mr. Smilo’s primary care physician, Dr. Gavin,

“filed a VAERS report identifying a potential causal and temporal relationship between the

administration of the [flu] vaccine and his [myasthenia gravis].” 54 Pet. Ex. 63 at 5.

In addition to his opinion that the flu vaccine caused Mr. Smilo’s myasthenia gravis, Dr.

DeAngelo also opined that “if he had not developed [myasthenia gravis,] . . . he would not have

required immunosuppressive treatment with azathioprine and, therefore, may have never died

from [HCC].” Pet. Ex. 18 at 1. For this reason, Dr. DeAngelo believed that “Mr. Smilo’s [HCC]

was likely either induced or accelerated in its progression via treatment with azathioprine.” Pet.

Ex. 55 at 4. Dr. DeAngelo cited Heron et al. 55 and Fortinsky et al. 56 who noted that azathioprine

was associated with HCC in patients with Crohn’s disease. Pet. Ex. 27 at 1; Pet. Ex. 24 at 1.

Additionally, Dr. DeAngelo noted Buell et al. 57 “report[ed] that azathioprine promotes

carcinogenesis independent of its immunosuppressive effects.” Pet. Ex. 55 at 2 (citing Pet. Ex.

56 at 4) (internal quotation marks omitted).

54

Dr. Gavin’s VAERS report does not include an opinion as to a causal association between

vaccination and Mr. Smilo’s myasthenia gravis. See Pet. Ex. 9.

55

Valérie Heron et al., Resected Hepatocellular Carcinoma in a Patient with Crohn’s Disease on

Azathioprine, 10 Case Reps. Gastroenterology 50 (2016).

56

Kyle J. Fortinsky et al., Metastatic Hepatocellular Carcinoma in a Patient with Crohn’s

Disease Treated with Azathioprine and Infliximab: A Case Report and Literature Review, 2014

Case Reps. Gastrointestinal Med. 1.

57

Joseph F. Buell et al., Malignancy After Transplantation, 80 Transplantation S254 (2005).

27

Thus, like Dr. Small, Dr. DeAngelo opined that Mr. Smilo “may never had developed

HCC if he had not been treated with azathioprine” given for treatment of his myasthenia gravis.

Pet. Ex. 18 at 15. Hence, Dr. DeAngelo concluded that “the [flu] vaccine was the original

precipitating event that lead to Mr. Smilo’s eventual decline from [myasthenia gravis] and []

death from a combination of his debilitated state and the advanced HCC.” Id.

iii. Loving Factor Six/Althen Prong Three

Regarding the temporal association between vaccination and onset of myasthenia gravis,

Dr. DeAngelo opined that “the onset or significant worsening of [Mr. Smilo’s] [myasthenia

gravis] symptomology did not manifest until approximately three (3) weeks following

administration of his [flu] vaccine.” Pet. Ex. 63 at 5. According to Dr. DeAngelo, Mr. Smilo

received his vaccination on October 17, 2016, and approximately one month after vaccination, he

saw Dr. Gavin and complained of a seven-day history of difficulty swallowing and eyelid droop.

Pet. Ex. 18 at 3-4.

Dr. DeAngelo further opined that this time frame is consistent with that reported in the

case studies of Chavez and Pougnier, Chung et al., and Lee et al., who reported an interval of

three days to six weeks between vaccination and onset of myasthenia gravis. Pet. Ex. 63 at 5

(citing Pet. Exs. 67-68, 72). In the case reported by Chung et al, onset was three days after

administration of the second HPV vaccination. Pet. Ex. 68 at 1. Three other case reports of

myasthenia gravis after HPV and BCG vaccinations were summarized, and onset in those cases

ranged from one month to six weeks. Id. at 3 tbl.1. Onset in the two cases of myasthenia gravis

following Covid-19 vaccination reported by Chavez and Pougnier and Lee et al. occurred two

days after the second dose (four weeks after the initial dose) and on the evening of the second

dose, respectively. Pet. Ex. 67 at 1;Pet. Ex. 72 at 1.

In conclusion, Dr. DeAngelo believed that “Mr. Smilo’s onset or significant worsening of

his [myasthenia gravis] symptomology [was] consistent with the timeframe espoused in the []

medical literature and [] consistent with [his] clinical experience in diagnosing post-infectious

autoimmune disease.” Pet. Ex. 63 at 5-6.

3. Respondent’s Expert, Dr. Eric Lancaster 58

a. Background and Qualifications

Dr. Lancaster is board-certified in neurology, neuromuscular medicine, and

electrodiagnostic studies, “with expertise in antibody-mediated neurological disorders.” Resp.

Ex. B at 1-2. He obtained a Ph.D. in Neuroscience and an M.D. from the University of Maryland

before completing an internship, neurology residency, and neuromuscular fellowships at the

University of Pennsylvania. Id. at 1; Resp. Ex. A at 1. Since 2010, he has worked as a

neurology professor at the University of Pennsylvania. Resp. Ex. B at 1. Dr. Lancaster has

authored over 30 peer-reviewed publications, with his “recent publications mostly concern[ing]

58

Respondent submitted four expert reports from Dr. Lancaster. Resp. Exs. A, C-E.

28

autoimmune neurological disorders and their mechanisms.” Resp. Ex. A at 1. “[His] clinic is

currently focused on autoimmune neurological diseases.” Id.

b. Opinion

Dr. Lancaster did not dispute diagnosis, but he disagreed that onset occurred after

vaccination and instead opined that Mr. Smilo had symptoms of myasthenia gravis prior to

vaccination that “evolved over several months . . . as commonly occurs with myasthenia gravis.”

Resp. Ex. A at 12-13. Additionally, Dr. Lancaster disputed causation, opining that “[t]here is no

reliable evidence that the seasonal [flu] vaccine causes myasthenia gravis.” Id. at 8. He

explained that “[t]he great majority of myasthenia cases are idiopathic, with a small group

triggered by tumors.” Id. at 9.

i. Loving Factor Four/Althen Prong One

1. Molecular Mimicry

In response to Petitioner’s experts’ opinions based on molecular mimicry, Dr. Lancaster

noted that Petitioner’s experts did not “explain which vaccine constituent would mimic the

AchR.” Resp. Ex. A at 9, 11. He explained that “molecular mimicry would require a vaccine

protein to have a strong 3-diminsinal resemblance to the structure of the human skeletal muscle

AchR in order to trigger cross-reactive antibodies.” Id. Dr. Lancaster further opined Petitioner’s

experts “ha[ve] not explained which protein in the vaccine is the mimic nor provided any

evidence that such mimicry has ever been reported in any human or animal.” Id.

2. Haptenization

Dr. Lancaster opined that there is no evidence that “a hapten effect occurs or that the

vaccine produces any immune response to the [AchR].” Resp. Ex. C at 3. Dr. Lancaster

explained that the articles cited by Petitioner in support of the hapten theory involve experiments

in animals where haptens were injected to illicit immune responses. Resp. Ex. E at 1. For

example, he noted the researchers in the Berd papers 59 “create[ed] hapten-modified tumor

vaccines by using a known hapten chemical (dinitrophenol) to modify melanoma cells. These

cells were injected along with other immune stimulating factors ([BCG]) into patients repeatedly

to . . . invoke autoimmunity to the tumor cells” for the purpose of treating cancer. Id. This is

very different from the facts and circumstances here, which involves a flu vaccine that is “not

designed to become haptenized to any human protein.” Id.

Similarly, Dr. Lancaster noted Gefen et al., 60 cited by Dr. DeAngelo, “d[id] not study or

mention myasthenia gravis” or “[flu] vaccination or [flu] proteins.” Resp. Ex. D at 3 (citing Pet.

Ex. 57). Gefen et al. studied “mice injected with foreign proteins (OVA and BSA) treated with a

59

See Pet. Exs. 64-65.

60

Tal Gefen et al., The Effect of Haptens on Protein-Carrier Immunogenicity, 144 Immunology

116 (2015).

29

series of haptens.” Id. (citing Pet. Ex. 57 at 2). Again, Dr. Lancaster concluded that it does not

provide any evidence about whether the flu vaccine, or any proteins in it, “can act as haptens to

the [AChR].” Id.

While Dr. Lancaster acknowledged that Bugelski generally discussed the process by

which haptens are formed, he emphasized that the article did not discuss myasthenia gravis or

describe any process by which “a vaccine protein [could] actually act as a hapten in any human

autoimmune disease.” Resp. Ex. C at 3. In fact, Dr. Lancaster stated this “idea that a vaccine

protein could be a hapten has never been demonstrated for any human autoimmune disease.” Id.

Breaking down Petitioner’s proposed hapten theory into subparts, Dr. Lancaster

explained that Dr. DeAngelo posited “that [flu] proteins can act as haptens, that this hapten

formation would specifically occur with the [AChR], and that this can actually cause myasthenia

gravis.” Resp. Ex. C at 3. Because “[t]his is a complex chain of improbable events offered

without any supporting evidence,” Dr. Lancaster concluded that it is “highly unlikely to be the

actual mechanism of [Mr. Smilo’s] illness.” Id.

3. Bystander Activation and Polyclonal Activation

Although Dr. DeAngelo offered the mechanisms of bystander activation and polyclonal

activation, Dr. Lancaster characterized these as “speculative” because Dr. DeAngelo offered no

supportive evidence. Resp. Ex. E at 2. Dr. Lancaster agreed that in general, these theories may

be relevant in the context of significant aggravation to explain how disease worsens. Id. He

explained that “[t]he idea is that [flu] vaccination and the response to [flu] antigens influences

cells that already make the antibodies relevant to myasthenia gravis to become more active.” Id.

However, he asserted that Dr. DeAngelo’s discussion of these theories is “vague and general”

and with “no specific evidence provided to support this hypothesis.” Id.

4. Medical literature 61

First, Dr. Lancaster addressed the medical literature cited by Petitioner’s expert, Dr.

Small. As Dr. Lancaster noted, the Agmon-Levin et al. article considered the question of

whether the flu vaccine could exacerbate some autoimmune illnesses, like lupus, but the authors

did not cite any evidence that the vaccine did worsen lupus. Resp. Ex. A at 8 (citing Pet. Ex. 13).

Further, the article did not discuss myasthenia gravis. Id. (citing Pet. Ex. 13). The Domigo et al.

article discussed one report of new onset myasthenia gravis and one report of exacerbation of

myasthenia gravis following the hepatitis B vaccine; however, Dr. Lancaster noted case reports

“represent the lowest level of medical evidence and could represent coincidences.” Id. (citing

Pet. Ex. 14). Moreover, the flu vaccine was not addressed. Id. (citing Pet. Ex. 14). As for the

Sanghani et al. abstract, Dr. Lancaster noted that “the rate of myasthenia [gravis] reported after

vaccination was similar to the rate . . . in the general population.” Id. (citing Pet. Ex. 15). In

addition, he stated that the study design was “less rigorous” than other studies addressing the

same issues. Id.

61

For a list of Dr. Lancaster’s criticism of 11 different articles cited by Petitioner, see Resp. Ex.

E at 5.

30

In response to the medical literature discussed by Petitioner’s experts, Dr. Lancaster cited

three “well-designed [and/or] placebo-controlled studies” confirming the safety of flu

vaccinations in patients with myasthenia gravis. Resp. Ex. A at 8-9. Zinman et al. presented a

case-series study of 3,667 hospital admissions for myasthenia gravis. Resp. Ex. A, Tab 4 at 1.

Of these admissions, there were “513 instances[], [where] hospitalization occurred within 42

weeks following [flu] vaccination in patients previously diagnosed with myasthenia gravis.” Id.

“Vaccination . . . was not found to be associated with exacerbations of [myasthenia gravis].” Id.

Strijbos et al. 62 conducted a double-blind randomized study in which they administered

either a flu vaccine or placebo to 47 patients with myasthenia gravis. Resp. Ex. A, Tab 2 at 1.

AChR antibody titers were measured before and after vaccination, and in the vaccination group,

they were unchanged after vaccination and did not differ from the non-vaccinated group. Id.

There was no exacerbation of myasthenia gravis, even in those patients who were receiving

immunosuppressive medications. Id. A similar study was performed by Tackenberg et al. in 62

patients, with half receiving the flu vaccination and the other half receiving a placebo. Pet. Ex.

40 at 1. Vaccination did not increase AChR antibody levels during the observation period of

three months and had no adverse effect on the clinical course in the patients with myasthenia

gravis. Id. at 6-7.

Next, Dr. Lancaster responded to medical literature cited by Dr. DeAngelo. Resp. Ex. A

at 11. As for the Schwimmbeck et al. article reporting cross-reactivity between a human AChR

α subunit and herpes simplex virus glycoprotein, Dr. Lancaster observed that the finding has

“limited significance” because the herpes simplex virus is “completely different” than the flu

virus. Id. (citing Pet. Ex. 36 at 1). Additionally, Dr. Lancaster opined that the mere

identification of a potential mimic does not translate to “actual clinical significance.” Id. In

other words, it is not known whether the herpes simplex virus can “trigger or worsen myasthenia

gravis.” Id.

Regarding the Stübgen paper, Dr. Lancaster offered similar criticism. Resp. Ex. A at 11.

Stübgen studied the hepatitis B virus, not the flu virus. Id. (citing Pet. Ex. 39). Further, Stübgen

reviewed medical articles, and therefore, Dr. Lancaster observed that it lacked the “rigor” of

Zinman et al., Strijbos et al., or Tackenberg et al. Id. (citing Pet. Exs. 39-40; Resp. Ex. A, Tab 2,

4). Next, He et al. dealt with the Japanese encephalitis vaccine, which Dr. Lancaster pointed out

is a different vaccine, and the study was done in a population (China) with “a higher incidence of

myasthenia [gravis] . . . compared to other countries,” implicating many potential confounders,

including “genetics, environment, differences in diagnosis, etc.” Id. (citing Pet. Ex. 26). In

contrast, Dr. Lancaster explained that the Zinman et al. study was larger and designed to find

62

Ellen Strijbos et al., A Prospective, Double-Blind, Randomized, Placebo-Controlled Study on

the Efficacy and Safety of Influenza Vaccination in Myasthenia Gravis, 37 Vaccine 919 (2019).

31

more subtle effects of vaccination in myasthenia gravis patients, and the study did not show

adverse effects of the flu vaccine in myasthenia gravis patients. 63 Id. at 12.

Dr. Lancaster found Dr. DeAngelo’s reference to the abstract by Hanumanthu et al. raised

several concerns. Resp. Ex. C at 3 (citing Pet. Ex. 58). As a preliminary issue, Dr. Lancaster

searched for the full article but was unable to find anything but an abstract. Id. Dr. Lancaster

stated that the abstract presented a summary of reports to VAERS about myasthenia gravis after

different vaccinations in children. Id. (citing Pet. Ex. 58). The most common vaccines reported

were HPV and hepatitis A/B. Id. (citing Pet. Ex. 58 at 2). They found the incidence of

myasthenia gravis was within the range expected for the general population. Id. (citing Pet. Ex.

58 at 2). Dr. Lancaster found “the study provides better evidence against the idea of vaccines

causing myasthenia gravis than for it.” Id. He further observed that the study was “very small

and subject to reporting bias.” Id. Dr. Lancaster opined that the much larger and better peer-

reviewed study by Zinman et al. was “far more convincing” and “its conclusions based on

sounder methods.” Id.

Dr. DeAngelo criticized the studies that did not show any association between the flu

vaccine and myasthenia gravis because the studies were too small, to which Dr. Lancaster

responded that the medical profession “should rely on the largest and best studies” available.

Resp. Ex. D at 2. Although he acknowledged the limitations based on study size, Dr. Lancaster

opined that “[i]n a study of a few hundred patients where no risk is detected, the effect would at

most be very small.” Id.

In summary, Dr. Lancaster stated that the medical literature cited by Petitioner does not

provide “convincing evidence that myasthenia gravis is caused or worsened by [the] [flu]

vaccination.” Resp. Ex. E at 5. “The available studies suggest that seasonal [flu] vaccines do

not trigger or worsen myasthenia gravis.” Id. at 6.

ii. Loving Factor Five/Althen Prong Two

Dr. Lancaster disagreed that the flu vaccination caused Mr. Smilo’s myasthenia gravis

because “[t]here is no reliable evidence that the seasonal [flu] vaccine causes myasthenia gravis.”

Resp. Ex. A at 8. Further, Dr. Lancaster opined that the flu vaccination did not cause Mr.

Smilo’s myasthenia gravis because onset of the illness occurred before vaccination. Id. at 6-7.

Dr. Lancaster also opined that there is no evidence to show that vaccination worsens myasthenia

gravis in those patients with the illness. Id. at 8-9; see Resp. Ex. A, Tabs 2, 4; Pet. Ex. 40.

According to Dr. Lancaster, Mr. Smilo’s myasthenia gravis began before vaccination and

“caused his symptoms of ptosis, double vision, fluctuating weakness, dysarthria[,] and

dysphagia. [His] symptoms evolved over several months and varied in severity during this time,

63

Dr. Lancaster also rejected Dr. DeAngelo’s reliance on PANDAS, or Pediatric Autoimmune

Neuropsychiatric Disorders Associated with Streptococcal Infections, “as an example of

molecular mimicry.” Resp. Ex. A at 12. The undersigned did not discuss that aspect of Dr.

DeAngelo’s opinions, as she agrees it is not relevant to the issues here. Therefore, the

undersigned will not discuss Dr. Lancaster’s responsive discussion.

32

as commonly occurs with myasthenia gravis.” Resp. Ex. E at 6. Dr. Lancaster cited Hehir and

Silvestri to explain that myasthenia gravis often presents with “drooping eyelids, [or] double or

blurry vision.” Id. at 4 (citing Resp. Ex. E, Tab 1 at 1-2). Hehir and Silvestri noted that “[t]he

majority of patients with [myasthenia gravis] first present with ocular symptoms,” which

includes “ptosis and/or diplopia without pupillary abnormalities.” Resp. Ex. E, Tab 1 at 1-2.

Additionally, Dr. Lancaster opined that the “[t]he median time to first myasthenic crisis is

8-12 months,” and he cited an article by Wendell and Levine for support. Resp. Ex. E at 4

(citing Resp. Ex. E, Tab 2 at 1). Moreover, “myasthenic crisis may be the initial presentation of

[myasthenia gravis] in one-fifth of patients.” Resp. Ex. E, Tab 2 at 1. Dr. Lancaster opined that

“[Mr. Smilo’s] symptoms evolved over several months and varied in severity during this time, as

commonly occurs with myasthenia gravis.” Id. at 6.

Dr. Lancaster disagreed with Dr. DeAngelo that Mr. Smilo’s death was in any way

caused by the medication azathioprine. Resp. Ex. A at 10-11. Dr. DeAngelo opined that Mr.

Smilo’s death was attributable to the medication azathioprine, prescribed as treatment for his

myasthenia gravis, and that this medication caused or contributed to the development of HCC

with obstructive jaundice, which lead to his death. Pet. Ex. 18 at 1, 5; Pet. Ex. 55 at 4. While

Dr. Lancaster agreed that “[a]zathioprine can increase the risk of cancer,” he explained that “this

risk gradually increases with cumulative doses and time” and “the cancer risk of taking the drug

for a couple of months is extremely small.” Resp. Ex. A at 10.

Further, Dr. Lancaster opined that Mr. Smilo had the liver mass before he began taking

azathioprine, as evidenced by a CT scan performed November 17, 2016, which showed liver

masses, the largest of which was 5.5 cm. Resp. Ex. A at 10; see Pet. Ex. 5a at 60. A follow-up

MRI was recommended, but it was not done. Resp. Ex. A at 10; see Pet. Ex. 5a at 60.

Subsequently, Mr. Smilo was diagnosed with HCC, and given this diagnosis, “it is obvious that

this was the same tumor” which “had most likely been slowly growing for months prior to

November 17, 2016 to reach this size.” Resp. Ex. A at 10. Since the tumor was present before

the medication was initiated, as evidenced by the CT scan, “it is impossible for azathioprine to

have caused the cancer.” Id. Mr. Smilo developed obstructive jaundice in March 2017, which

Dr. Lancaster opined “is the logical, predictable[,] and normal history of this type of cancer.” Id.

Dr. Lancaster disagreed with Dr. DeAngelo’s assertions that the tumors seen on Mr.

Smilo’s initial CT scan on November 7, 2016 were not the same ones seen on the later CT done

in March 2017, or that the tumors seen on the second CT were new or different than the earlier

tumors. Resp. Ex. C at 2. He also disagreed with Dr. DeAngelo that the liver masses seen on the

initial CT scan were benign or underwent malignant transformation due to treatment with the

medication azathioprine. Id. Dr. Lancaster found this scenario extremely unlikely given the

facts presented here. Id.

According to Greten et al., 64 cited by Dr. Lancaster, median survival in patients with liver

cancer is only 11 months because “liver cancer is aggressive, rapidly progressive[,] and deadly.”

64

TF Greten et al., Survival Rate in Patients with Hepatocellular Carcinoma: A Retrospective

Analysis of 389 Patients, 92 Brit. J. Cancer 1862 (2005).

33

Resp. Ex. A at 10-11 (citing Resp. Ex. A, Tab 6 at 1). Dr. Lancaster believed that “[t]he

enlargement of [Mr. Smilo’s] tumor [was] very unlikely to have been significantly influenced by

[his] myasthenia gravis or its treatment.” Id. at 11. Thus, Dr. Lancaster concluded that “[t]here

is no plausible connection between the [flu] vaccine and [Mr. Smilo’s] death from cancer.” Id.

In summary, Dr. Lancaster concluded that more likely than not “[Mr. Smilo] had

myasthenia gravis, which caused his symptoms of ptosis, double vision, fluctuating weakness,

dysarthria[,] and dysphagia. [His] symptoms evolved over several months and varied in severity

during this time, as commonly occurs with myasthenia gravis.” Resp. Ex. A at 12-13; Resp. Ex.

C at 4; Resp. Ex. D at 3; Resp. Ex. E at 6. Further, Dr. Lancaster did not agree that the

vaccination caused or contributed to Mr. Smilo’s death. Resp. Ex. A at 13; Resp. Ex. C at 4;

Resp. Ex. D at 3-4; Resp. Ex. E at 6. The cause of death was liver cancer, and Dr. Lancaster

opined that “[t]here is no reasonable causal connection between [the] [flu] vaccination and [Mr.

Smilo’s] liver cancer.” Resp. Ex. A at 13; Resp. Ex. C at 4; Resp. Ex. D at 3-4; Resp. Ex. E at 6.

iii. Loving Factor Six/Althen Prong Three

Dr. Lancaster opined that the onset of Mr. Smilo’s myasthenia gravis was prior to his flu

vaccination, and therefore, the vaccination could not have caused his illness. Resp. Ex. A at 6,

13. Dr. Lancaster placed onset of Mr. Smilo’s myasthenia gravis when he developed ptosis,

explaining that “[p]tosis is a classic symptom of myasthenia” gravis and “often the presenting

symptom.” Resp. Ex. C at 2.

Dr. Lancaster’s opinion that onset predated vaccination on October 17, 2016 was based

on the medical records of four different health care providers. Resp. Ex. A at 6-7. The first three

are dated November 17, 2016. Id. And the first of these was Dr. Floyd’s record stating that Mr.

Smilo reported that his right eye droop began three months before. Id. at 6 (citing Pet. Ex. 4 at

27-29). Dr. Floyd also wrote that his dysphagia had been present since endoscopy the previous

September. Id. (citing Pet. Ex. 4 at 27-29). The second record is an ED triage note by Nurse

Jellison, stating that Mr. Smilo reported “he had been having trouble with [his] right eye for

months.” Id. at 7 (quoting Pet. Ex. 5a at 40). Mr. Smilo also reported having “some difficulty

with speech for the last week, states increasingly constant, [Petitioner] reports worse over the last

few days. [Mr. Smilo] states feeling like he had a phlegm ball in the back of his throat, so he had

an EGD at the end of September, state[s] . . . worsening problems this week however.” Id.

(quoting Pet. Ex. 5a at 40). Mr. Smilo reported onset three months prior to this visit on

November 17, 2016. Id. (citing Pet. Ex. 5a at 43). Third, while in the ED, Mr. Smilo was seen

by Dr. Goebel, who documented that “[three] months ago [Mr. Smilo] noticed [right] drooping

eye lid” and “also had trouble swallowing since his endoscopy in September.” Id. (quoting Pet.

Ex. 5a at 54-55). The fourth note is from Dr. Catalano, the neurologist who diagnosed Mr. Smilo

with myasthenia gravis, on December 12, 2016. Id. (citing Pet. Ex. 6 at 12-14). On December

12, 2016, Mr. Smilo reported that he had had trouble swallowing since August 2016, and that he

had right eyelid drooping noted by Petitioner in the spring of 2016. Id. (citing Pet. Ex. 6 at 12).

Thus, Dr. Lancaster opined that “these notes [] clearly date ptosis and dysphagia prior to

the vaccination.” Resp. Ex. A at 7. He placed significant emphasis on Dr. Catalano’s records

due to his specialty of neurology, and as such, “[h]e was the person best positioned to understand

34

the diagnosis and ask the most important questions.” Id. And Dr. Lancaster did not believe that

Dr. Gavin’s VAERS report, which was prepared later in time, invalidated the more

contemporaneous records. Resp. Ex. C at 2.

As for Dr. Small’s argument that Mr. Smilo’s did not have ptosis prior to vaccination

because his treating optometrist (Dr. Ives) did not document it, Dr. Lancaster disagreed. Resp.

Ex. A at 9. Notably, Dr. Lancaster observed that Dr. Ives did not document ptosis even after Mr.

Smilo was diagnosed with myasthenia gravis while his other records document ptosis during this

time. Id. Further, Dr. Ives did not document a detailed history, or note that he ever questioned

Mr. Smilo about ptosis. Id. For these reasons, Dr. Lancaster did not give as much weight to the

records of Dr. Ives, and gave more weight to the detailed histories and records discussed above

by a nurse and three physicians who all documented a consistent history taken from their patient.

Id.

Dr. Lancaster also disagreed with Dr. DeAngelo’s position that because Mr. Smilo’s

ptosis and dysphagia were not documented before vaccination, the post-vaccination records

placing onset of these symptoms prior to vaccination are suspect or inaccurate. Resp. Ex. D at 1.

For example, on November 17, 2016, Dr. Floyd documented that Mr. Smilo reported that his

ptosis had been present for three months. Id. (citing Pet. Ex. 4 at 27). Dr. Lancaster stated that

there is no reason to “question Dr. [Floyd’s] competence in gathering this history.” Id.

Moreover, similar histories were recorded by other health care providers. Id. at 2. “The idea that

somehow the symptoms need[ed] to be reported prior to vaccination and not just occur prior to

vaccination is not [] reasonable . . . .” Id.

Regarding alternative cause for Mr. Smilo’s ptosis, Dr. Lancaster explained that ptosis

was “the first sign of [Mr. Smilo’s] myasthenia [gravis].” Resp. Ex. A at 7. Dr. Lancaster

rejected the idea that Mr. Smilo would have developed ptosis “just a few months prior to a

myasthenic crisis (with positive AchR antibodies) and then that it coincidentally improved with

treatment of [] myasthenia [gravis].” Id.

Lastly, Dr. Lancaster discussed the affidavits of Petitioner and Dr. Gavin. Resp. Ex. E at

2-3. To summarize, in Petitioner’s affidavit, dated August 9, 2021, she averred that her husband,

Mr. Smilo, had no symptoms of myasthenia gravis before his flu vaccination. Id. at 2 (citing Pet.

Ex. 61). Petitioner also had no recollection of telling Mr. Smilo’s physicians that he had

symptoms before he received the flu vaccination. Id. (citing Pet. Ex. 61). Dr. Gavin’s affidavit,

dated August 13, 2021, indicated that he did not see Mr. Smilo when he presented to the office

on November 17, 2016, and that the note was made by another physician, Dr. Floyd, who is no

longer with the practice. Id. (citing Pet. Ex. 62). In the affidavit, Dr. Gavin interpreted Dr.

Floyd’s note. Id. (citing Pet. Ex. 62). Dr. Gavin also summarized his prior office records and

concluded that Dr. Floyd’s noted stating that Mr. Smilo had a droopy eyelid for three months

was “erroneous.” Pet. Ex. 62 at 3.

In response, Dr. Lancaster disagreed with Dr. Gavin’s interpretation of Dr. Floyd’s note

and did not believe that it was erroneous. Resp. Ex. E at 2-3. Instead, Dr. Lancaster viewed it as

consistent with notes written by other providers on November 17, 2016. Id. at 3. Dr. Lancaster

also opined that Dr. Floyd’s record included Mr. Smilo’s complaint that “he couldn’t swallow,”

35

and that this symptom was “also most likely a symptom of myasthenia gravis.” Id. at 2-3. In

summary, Dr. Lancaster believed that the contemporaneous medical records were more accurate

and reliable than the affidavits made over four years after the events in question. Id.

VI. LEGAL FRAMEWORK

A. Standard of Adjudication—Factual Issues

A petitioner must prove, by a preponderance of the evidence, the factual circumstances

surrounding her claim. § 13(a)(1)(A). To resolve factual issues, the special master must weigh

the evidence presented, which may include contemporaneous medical records and testimony.

See Burns v. Sec’y of Health & Hum. Servs., 3 F.3d 415, 417 (Fed. Cir. 1993) (explaining that a

special master must decide what weight to give evidence including oral testimony and

contemporaneous medical records). Contemporaneous medical records, “in general, warrant

consideration as trustworthy evidence.” Cucuras v. Sec’y of Health & Hum. Servs., 993 F.2d

1525, 1528 (Fed. Cir. 1993). But see Kirby v. Sec’y of Health & Hum. Servs., 997 F.3d 1378,

1382 (Fed. Cir. 2021) (rejecting the presumption that “medical records are accurate and complete

as to all the patient’s physical conditions”); Shapiro v. Sec’y of Health & Hum. Servs., 101 Fed.

Cl. 532, 538 (2011) (“[T]he absence of a reference to a condition or circumstance is much less

significant than a reference which negates the existence of the condition or circumstance.”

(quoting Murphy v. Sec’y of Health & Hum. Servs., 23 Cl. Ct. 726, 733 (1991), aff’d per curiam,

968 F.2d 1226 (Fed. Cir. 1992))), recons. den’d after remand, 105 Fed. Cl. 353 (2012), aff’d

mem., 503 F. App’x 952 (Fed. Cir. 2013).

There are situations in which compelling testimony may be more persuasive than written

records, such as where records are deemed to be incomplete or inaccurate. Campbell v. Sec’y of

Health & Hum. Servs., 69 Fed. Cl. 775, 779 (2006) (“[L]ike any norm based upon common

sense and experience, this rule should not be treated as an absolute and must yield where the

factual predicates for its application are weak or lacking.”); Lowrie v. Sec’y of Health & Hum.

Servs., No. 03-1585V, 2005 WL 6117475, at *19 (Fed. Cl. Spec. Mstr. Dec. 12, 2005)

(“[W]ritten records which are, themselves, inconsistent, should be accorded less deference than

those which are internally consistent.” (quoting Murphy, 23 Cl. Ct. at 733)). Ultimately, a

determination regarding a witness’s credibility is needed when determining the weight that such

testimony should be afforded. Andreu v. Sec’y of Health & Hum. Servs., 569 F.3d 1367, 1379

(Fed. Cir. 2009); Bradley v. Sec’y of Health & Hum. Servs., 991 F.2d 1570, 1575 (Fed. Cir.

1993).

Despite the weight afforded to medical records, special masters are not bound rigidly by

those records in determining onset of a petitioner’s symptoms. Valenzuela v. Sec’y of Health &

Hum. Servs., No. 90-1002V, 1991 WL 182241, at *3 (Fed. Cl. Spec. Mstr. Aug. 30, 1991); see

also Eng v. Sec’y of Health & Hum. Servs., No. 90-1754V, 1994 WL 67704, at *3 (Fed. Cl.

Spec. Mstr. Feb. 18, 1994) (“[Section 13(b)(2)] must be construed so as to give effect also to §

13(b)(1) which directs the special master or court to consider the medical records (reports,

diagnosis, conclusions, medical judgment, test reports, etc.), but does not require the special

master or court to be bound by them.” (emphasis omitted)).

36

B. Standards for Adjudication—Causation

The Vaccine Act was established to compensate vaccine-related injuries and deaths. §

10(a). “Congress designed the Vaccine Program to supplement the state law civil tort system as

a simple, fair and expeditious means for compensating vaccine-related injured persons. The

Program was established to award ‘vaccine-injured persons quickly, easily, and with certainty

and generosity.’” Rooks v. Sec’y of Health & Hum. Servs., 35 Fed. Cl. 1, 7 (1996) (quoting

H.R. Rep. No. 908 at 3, reprinted in 1986 U.S.C.C.A.N. at 6287, 6344).

Petitioner’s burden of proof is by a preponderance of the evidence. § 13(a)(1). The

preponderance standard requires a petitioner to demonstrate that it is more likely than not that the

vaccine at issue caused the injury. Moberly v. Sec’y of Health & Hum. Servs., 592 F.3d 1315,

1322 n.2 (Fed. Cir. 2010). Proof of medical certainty is not required. Bunting v. Sec’y of Health

& Hum. Servs., 931 F.2d 867, 873 (Fed. Cir. 1991). Petitioner need not make a specific type of

evidentiary showing, i.e., “epidemiologic studies, rechallenge, the presence of pathological

markers or genetic predisposition, or general acceptance in the scientific or medical communities

to establish a logical sequence of cause and effect.” Capizzano v. Sec’y of Health & Hum.

Servs., 440 F.3d 1317, 1325 (Fed. Cir. 2006). Instead, Petitioner may satisfy her burden by

presenting circumstantial evidence and reliable medical opinions. Id. at 1325-26.

In particular, Petitioner must prove that the vaccine was “not only [the] but-for cause of

the injury but also a substantial factor in bringing about the injury.” Moberly, 592 F.3d at 1321

(quoting Shyface v. Sec’y of Health & Hum. Servs., 165 F.3d 1344, 1352-53 (Fed. Cir. 1999));

see also Pafford v. Sec’y of Health & Hum. Servs., 451 F.3d 1352, 1355 (Fed. Cir. 2006). The

received vaccine, however, need not be the predominant cause of the injury. Shyface, 165 F.3d

at 1351. A petitioner who satisfies this burden is entitled to compensation unless Respondent

can prove, by a preponderance of the evidence, that the vaccinee’s injury is “due to factors

unrelated to the administration of the vaccine.” § 13(a)(1)(B). However, if a petitioner fails to

establish a prima facie case, the burden does not shift. Bradley, 991 F.2d at 1575.

“Regardless of whether the burden ever shifts to the [R]espondent, the special master

may consider the evidence presented by the [R]espondent in determining whether the [P]etitioner

has established a prima facie case.” Flores v. Sec’y of Health & Hum. Servs., 115 Fed. Cl. 157,

162-63 (2014); see also Stone v. Sec’y of Health & Hum. Servs., 676 F.3d 1373, 1379 (Fed. Cir.

2012) (“[E]vidence of other possible sources of injury can be relevant not only to the ‘factors

unrelated’ defense, but also to whether a prima facie showing has been made that the vaccine

was a substantial factor in causing the injury in question.”); de Bazan v. Sec’y of Health & Hum.

Servs., 539 F.3d 1347, 1353 (Fed. Cir. 2008) (“The government, like any defendant, is permitted

to offer evidence to demonstrate the inadequacy of the [P]etitioner’s evidence on a requisite

element of the [P]etitioner’s case-in-chief.”); Pafford, 451 F.3d at 1358-59 (“[T]he presence of

multiple potential causative agents makes it difficult to attribute ‘but for’ causation to the

vaccination. . . . [T]he Special Master properly introduced the presence of the other unrelated

contemporaneous events as just as likely to have been the triggering event as the vaccinations.”).

To receive compensation through the Program, Petitioner must prove either (1) that Mr.

Smilo suffered a “Table Injury”—i.e., an injury listed on the Vaccine Injury Table—

37

corresponding to a vaccine that he received, or (2) that Mr. Smilo suffered an injury that was

actually caused by a vaccination. See §§ 11(c)(1), 13(a)(1)(A); Capizzano, 440 F.3d at 1319-20.

Because Petitioner does not allege Mr. Smilo suffered a Table Injury, she must prove a vaccine

Mr. Smilo received caused Mr. Smilo’s injury. To do so, Petitioner must establish, by

preponderant evidence: “(1) a medical theory causally connecting the vaccination and the injury;

(2) a logical sequence of cause and effect showing that the vaccination was the reason for the

injury; and (3) a showing of a proximate temporal relationship between vaccination and injury.”

Althen, 418 F.3d at 1278.

The causation theory must relate to the injury alleged. Petitioner must provide a sound

and reliable medical or scientific explanation that pertains specifically to this case, although the

explanation need only be “legally probable, not medically or scientifically certain.” Knudsen v.

Sec’y of Health & Hum. Servs., 35 F.3d 543, 543, 548-49 (Fed. Cir. 1994). Petitioner cannot

establish entitlement to compensation based solely on her assertions; rather, a vaccine claim must

be supported either by medical records or by the opinion of a medical doctor. § 13(a)(1). In

determining whether Petitioner is entitled to compensation, the special master shall consider all

materials in the record, including “any . . . conclusion, [or] medical judgment . . . which is

contained in the record regarding . . . causation.” § 13(b)(1)(A). The undersigned must weigh

the submitted evidence and the testimony of the parties’ proffered experts and rule in Petitioner’s

favor when the evidence weighs in her favor. See Moberly, 592 F.3d at 1325-26 (“Finders of

fact are entitled—indeed, expected—to make determinations as to the reliability of the evidence

presented to them and, if appropriate, as to the credibility of the persons presenting that

evidence.”); Althen, 418 F.3d at 1280 (noting that “close calls” are resolved in Petitioner’s

favor).

Testimony that merely expresses the possibility—not the probability—is insufficient, by

itself, to substantiate a claim that such an injury occurred. See Waterman v. Sec’y of Health &

Hum. Servs., 123 Fed. Cl. 564, 573-74 (2015) (denying Petitioner’s motion for review and

noting that a possible causal link was not sufficient to meet the preponderance standard). The

Federal Circuit has made clear that the mere possibility of a link between a vaccination and a

petitioner’s injury is not sufficient to satisfy the preponderance standard. Moberly, 592 F.3d at

1322 (emphasizing that “proof of a ‘plausible’ or ‘possible’ causal link between the vaccine and

the injury” does not equate to proof of causation by a preponderance of the evidence); Boatmon

v. Sec’y of Health & Hum. Servs., 941 F.3d 1351, 1359-60 (Fed. Cir. 2019). While certainty is

by no means required, a possible mechanism does not rise to the level of preponderance.

Moberly, 592 F.3d at 1322; see also de Bazan, 539 F.3d at 1351.

C. Standards for Adjudication—Significant Aggravation

The elements of an off-Table significant aggravation case are set forth in Loving. See

Loving, 86 Fed. Cl. at 142-44; see also W.C. v. Sec’y of Health & Hum. Servs., 704 F.3d 1352,

1357 (Fed. Cir. 2013) (holding that “the Loving case provides the correct framework for

evaluating off-table significant aggravation claims”). The Loving court combined the Althen

test, which defines off-Table causation cases, with a test from Whitecotton. Whitecotton v.

Sec’y of Health & Hum. Servs., 17 F.3d 374 (Fed. Cir. 1994), rev’d sub nom., Shalala v.

38

Whitecotton, 514 U.S. 268 (1995) (concerning on-Table significant aggravation cases). The

resultant test has six components, which are:

(1) the person’s condition prior to administration of the vaccine, (2) the person’s

current condition (or the condition following the vaccination if that is also

pertinent), (3) whether the person’s current condition constitutes a ‘significant

aggravation’ of the person’s condition prior to vaccination, (4) a medical theory

causally connecting such a significant worsened condition to the vaccination, (5) a

logical sequence of cause and effect showing that the vaccination was the reason

for the significant aggravation, and (6) a showing of a proximate temporal

relationship between the vaccination and the significant aggravation.

Loving, 86 Fed. Cl. at 144.

The statute defines “significant aggravation” as “any change for the worse in a pre-

existing condition which results in markedly greater disability, pain, or illness accompanied by

substantial deterioration in health.” § 33(4).

VII. ANALYSIS

A. Onset

The literature filed by the parties establishes that generally, initial symptoms of

myasthenia gravis include drooping of one or both eyelids (ptosis). Pet. Ex. 12 at 1-2. Most

patients present with ocular symptoms, including ptosis. Resp. Ex. E, Tab 1 at 1-2. Although

there is no documentation in Mr. Smilo’s medical records of ptosis prior to the date of

vaccination (October 17, 2016), medical records after vaccination from four different health care

providers independently document that Mr. Smilo reported that he had the symptom of ptosis

several months prior to vaccination.

Approximately one month after vaccination, on November 17, 2016, Mr. Smilo was seen

by Dr. Floyd. Her note documents “eye drooping [one] week,” as well as “right eye droop

[three] months.” Pet. Ex. 4 at 27 (emphasis omitted). The same day, Mr. Smilo was seen in the

ED for complaints of slurred speech and right side eye droop. Triage Nurse Jellison wrote that

Mr. Smilo “states he has been having problems with his right eye for months.” Pet. Ex. 5a at 40.

Nurse Jellison also reported that “onset time was [three] months ago.” Id. at 43. While in the

ED, Mr. Smilo was also seen by Dr. Goebel, who wrote, “[three] months ago noticed [right]

drooping eyelid.” Id. at 55. Moving forward to December 12, 2016, Mr. Smilo saw neurologist

Dr. Catalano, who wrote that Mr. Smilo’s wife, Petitioner, “noted right eyelid drooping in the

spring of 2016.” Pet. Ex. 6 at 12.

To the extent that Petitioner’s affidavit or Dr. Gavin’s affidavit are inconsistent with

and/or contradict the health care providers’ histories documented in the contemporaneous

medical records and objective physical examinations or diagnostic testing, the undersigned

defers to the contemporaneous records as the most reliable source of information. See Cucuras,

993 F.2d at 1528 (noting that “the Supreme Court counsels that oral testimony in conflict with

39

contemporaneous documentary evidence deserves little weight”); Doe/70 v. Sec’y of Health &

Hum. Servs., 95 Fed. Cl. 598, 608 (2010); Stevens v. Sec’y of Health & Hum. Servs., No. 90-

221V, 1990 WL 608693, at *3 (Cl. Ct. Spec. Mstr. Dec. 21, 1990) (noting that “clear, cogent,

and consistent testimony can overcome such missing or contradictory medical records”); Vergara

v. Sec’y of Health & Hum. Servs., No. 08-882V, 2014 WL 2795491, at *4 (Fed. Cl. Spec. Mstr.

May 15, 2014) (“Special Masters frequently accord more weight to contemporaneously-recorded

medical symptoms than those recorded in later medical histories, affidavits, or trial testimony.”).

This finding also extends to lay witness affidavits and testimony. Other special masters

faced with similar situations have found contemporaneous medical records more persuasive than

the affidavits and testimonies of lay witnesses. See, e.g., Rote v. Sec’y of Health & Hum. Servs.,

No. 90-036V, 1992 WL 165970, at *5 (Cl. Ct. Spec. Mstr. July 1, 1992) (finding the lay witness

testimony insufficient to overcome the weight of the contemporaneous medical records);

Bergman v. Sec’y of Health & Hum. Servs., No. 90-1252V, 1992 WL 78671, at *4 (Cl. Ct. Spec.

Mstr. Mar. 31, 1992) (same); Daiza v. Sec’y of Health & Hum. Servs., No. 90-1188V, 1992 WL

59709, at *4 (Cl. Ct. Spec. Mstr. Mar. 5, 1992) (same).

While the undersigned has reviewed the affidavits of Petitioner and Dr. Gavin on the

issue of onset, these accounts were documented in August 2021, almost five years after the

events in question. In comparison, the medical records prepared contemporaneously by a nurse

and three physicians documented that Mr. Smilo and/or Petitioner reported that his ptosis began

three months prior to November 17, 2016. This places onset of the ptosis approximately August

2016, and based on Dr. Catalano’s note, as early as spring 2016. The fact that at least three of

the four records place onset at the same time (three months before) is compelling evidence,

because they are consistent even though they are written by different providers. In their totality,

these records provide persuasive evidence of onset. Thus, the undersigned finds that the initial

manifestation of Mr. Smilo’s myasthenia gravis was ptosis, which occurred three months prior to

his presentation at the ED on November 17, 2016, and perhaps as early as the spring of 2016.

Regardless of whether onset was spring 2016 or August 2016, onset of Mr. Smilo’s myasthenia

gravis predated vaccination.

B. Six Month Severity Requirement

To be entitled to compensation, Petitioner must show Mr. Smilo

(i) suffered the residual effects or complications of such illness, disability, injury,

or condition for more than 6 months after the administration of the vaccine, or (ii)

died from the administration of the vaccine, or (iii) suffered such illness,

disability, injury, or condition from the vaccine which resulted in inpatient

hospitalization and surgical intervention.

§ 11(c)(1)(D).

Here, Petitioner must prove by preponderant evidence that Mr. Smilo either “died

from the administration of the vaccine,” or “suffered such illness, disability, injury, or

40

condition from the vaccine which resulted in inpatient hospitalization and surgical

intervention.” Id. at § 11(c)(1)(D)(ii)-(iii).

Petitioner contends that there are two reasons that she has satisfied the Vaccine Act’s

statutory severity requirement: (1) Mr. Smilo’s myasthenia gravis injury “resulted in his

hospitalization at Latrobe Area Hospital for myasthenic crisis and surgical intervention by means

of PEG tube placement as a result of his severe myasthenic dysphagia;” and (2) “Mr. Smilo’s

myasthenia gravis was a significant contributing fact in bringing about [his] death” as “detailed

in the expert reports of Dr. Small and Dr. DeAngelo.” Pet. Mot. at 23.

1. Inpatient Hospitalization and Surgical Intervention

First, with regard to “inpatient hospitalization,” Petitioner contends “Mr. Smilo’s alleged

vaccine-related myasthenia gravis/myasthenic crisis resulted in him being admitted for inpatient

care at Latrobe Hospital from December 22, 2016 through January 13, 2017.” Pet. Reply at 1.

During this hospitalization, on January 3, 2017, Mr. Smilo underwent PEG tube placement

surgery “to improve his declining health and alter the course of his myasthenic dysphagia.” Id.

at 2. And after, Mr. Smilo remained hospitalized for monitoring of his postoperative condition.

Id. Thus, Petitioner concludes this hospitalization meets the definition of “inpatient

hospitalization.” Id.

Next, Petitioner relied upon Spooner to interpret whether Mr. Smilo’s PEG tube

placement surgery constitutes a “surgical intervention.” Pet. Reply at 2 (citing Spooner v. Sec’y

of Health & Hum. Servs., No. 13-159V, 2014 WL 504728 (Fed. Cl. Spec. Mstr. Jan. 16, 2014)).

In Spooner, “surgical intervention” was defined as “the treatment of a disease, injury, and

deformity with instruments or by the hand of a surgeon to improve health or alter the course of a

disease.” Id. (quoting Spooner, 2014 WL 504728, at *10) (citing Leming v. Sec’y of Health &

Hum. Servs., 154 Fed. Cl. 325, 332-34 (2021)). Given this definition, Petitioner contends the

PEG tube placement would be considered a “surgical procedure” and a “surgical intervention.”

Id.

Petitioner states the PEG procedure was “surgical” because “(1) it was performed by a

surgeon;” “(2) an operative report was authored by the surgeon, Dr. Ted Matthews, to document

the procedure;” “(3) it involved the incision and insertion of an instrument into the stomach;

namely, an introducer needle with catheter was passed through the incision into the stomach;”

“(4) it involved use of anesthesia and Mr. Smilo was taken to postanesthesia care unit for

monitoring following the procedure;” and “(5) the hospital treated the procedure as ‘surgical.’”

Pet. Reply at 3. Petitioner also asserts the PEG tube placement was a “surgical intervention”

using the Leming definition: “only those surgical procedures that are administered to directly

treat a condition once it has been diagnosed.” Id. (quoting Leming, 154 Fed. Cl. at 333).

Petitioner explained the PEG tube placement was necessary to treat Mr. Smilo’s dysphagia,

which was due to Mr. Smilo’s myasthenia gravis, and thus, Mr. Smilo’s PEG tube placement

surgery “meet[s] the definition of ‘surgical intervention’ as a procedure ‘undertaken to alter the

course of a disease’ and/or ‘administered to directly treat a condition once it has been

diagnosed.’” Id.

41

Respondent notes Mr. Smilo’s death on April 6, 2017 occurred less than six months after

his flu vaccination on October 17, 2016. Resp. Response at 13. Respondent contends that Mr.

Smilo’s hospitalization and “PEG tube placement does not constitute ‘inpatient hospitalization

and surgical intervention.’” Id. at 14. Respondent cites three reasons that the PEG tube insertion

does not fulfill the Act’s third provision related to “inpatient hospitalization and surgical

intervention.” Id. at 14-17. First, Respondent contends Mr. Smilo’s PEG tube placement did not

require ongoing hospitalization. Id. at 15. Respondent argues that because Mr. Smilo was

already hospitalized for a myasthenic crisis, his PEG tube placement was “inpatient.” and “the

procedure itself did not necessitate inpatient hospitalization.” Id. Mr. Smilo remained

hospitalized an additional two weeks after the PEG tube placement for ongoing treatment of his

myasthenia gravis. Id.

With regard to “surgical intervention,” Respondent contends that a PEG tube placement

does not constitute “surgery.” Resp. Response at 15. Respondent acknowledges that a surgeon

was involved, and that a needle was used, and that these factors weigh in favor of defining the

procedure as a surgery. Id. at 15-16. However, Respondent contends that because the procedure

was done in an endoscopy suite, that topical lidocaine was used, and because Mr. Smilo received

conscious sedation instead of general anesthesia, the facts do not weigh in favor of a finding that

the procedure constituted “surgery.” Id. at 14-16.

Moreover, Respondent argues that insertion of a PEG tube does not meet the Act’s

definition of “intervention” because the PEG tube was not “the treatment for Mr. Smilo’s

[myasthenia gravis].” Resp. Response at 16. In support of this position, Respondent cites the

legislative history of the Act, which indicates that the provision “inpatient hospitalization and

surgical intervention” was made part of the Act to ensure that surgery for intussusception would

be covered, and to serve as a “suitable statutory proxy for a serious injury equivalent to more

than six months of pain and suffering.” Id. (quoting Spooner, 2014 WL 504728, at *11) (citing

Leming, 154 Fed. Cl. at 333-34).

2. Death

Petitioner contends “[her] experts, Dr. Small and Dr. DeAngelo, propose that Mr. Smilo’s

[flu] vaccine caused or significantly aggravated his myasthenia gravis and this vaccine injury

sequela acted in conjunction with his underlying liver cancer to bring about his death.” Pet

Reply at 3. Petitioner explains the “[flu] vaccine was a substantial factor in causing [Mr.

Smilo’s] death,” and cited Mr. Smilo’s death certificate, which listed myasthenia gravis as a

“significant condition contributing to death,” and the opinions of Dr. Small and Dr. DeAngelo

for support. Id. at 3-4 (quoting Pet. Ex. 1 at 1).

Dr. Small opined that “within a reasonable degree of medical certainty[,] [Mr. Smilo’s]

myasthenia gravis and resulting sequela were a significant contributing factor in bringing about

his death.” Pet. Ex. 10 at 5. According to Dr. Small, Mr. Smilo’s “severe dysphagia did not

allow him to tolerate nutrition through normal means of oral feeding requiring gastrostomy tube

placement, and a resulting weight loss of 70 pounds.” Id. While some of his symptoms

improved with treatment, Mr. Smilo’s “dysphagia induced weight loss and other myasthenia

gravis sequela caused a very weakened and debilitated general state,” which made him

42

“vulnerable to a significant co-existent disease.” Id. at 5-6. Mr. Smilo was “diagnosed with liver

cancer in early April 2017,” and “died on April 6, 2017.” Id. at 6. His death certificate indicates

that myasthenia gravis was “a significant condition contributing to death.” Id. Dr. Small

concluded that “[t]he sequence of events from [flu] vaccination to development of significant

generalized myasthenia gravis resulted in a rapid and pronounced decline in his overall health

and must be considered a significant contributing factor in bringing about his death.” Id. Dr.

Small holds this opinion regardless of whether the vaccination caused or significantly aggravated

Mr. Smilo’s myasthenia gravis. Id.

Similarly, Dr. DeAngelo opined that Mr. Smilo’s reaction to his vaccination was “the

original precipitating event that led to [his] eventual decline from [myasthenia gravis] and

eventual death from a combination of his debilitated state and advanced HCC.” Pet. Ex. 18 at

15. By the time that Mr. Smilo was diagnosed with cancer, he had “severe dysphagia with an

inability to eat[] and resultant PEG tube placement,” with a resulting weight loss of 70 pounds.

Id. “His debilitated state, along with his immunosuppression, further accelerated his decline and

precluded aggressive treatment of his [then] advanced malignancy.” Id.

In addition to his opinion that Mr. Smilo’s myasthenia gravis led to a debilitated state that

contributed to his death, Dr. DeAngelo also opined that Mr. Smilo “may have never developed

HCC if he had not been treated with [] azathioprine prescribed to treat his aggressive myasthenia

symptomatology.” Pet. Ex. 18 at 15. He cited Buell et al., who “report[ed] that azathioprine

promotes carcinogenesis independent of its immunosuppressive effects.” Pet. Ex. 55 at 2 (citing

Pet. Ex. 56 at 4) (internal quotation marks omitted). Buell et al. also states that azathioprine, an

antimetabolite, “has long been recognized as an etiologic factor in the development of

neoplasia.” Pet. Ex. 56 at 4. The authors note its role in the “increased risk of late nonmelanotic

skin malignancies” as well as the “development of myelodysplastic syndrome.” Id. However,

the authors did not state that azathioprine causes or contributes to the development of or rapid

progression of liver cancer. Overall, Dr. DeAngelo associates Mr. Smilo’s rapid progression of

his liver cancer to the medication azathioprine. See Pet. Ex. 55 at 2; Pet. Ex. 18 at 15.

Respondent contends “[t]here is no reliable evidence that Mr. Smilo’s [myasthenia

gravis] was either a but-for cause or a substantial factor in bringing about his death.” Resp.

Response at 17. First, Respondent cites to the death certification and argues that it did not

indicate myasthenia gravis “medically contributed to his death.” Id. “There is no autopsy report,

medical analysis, or other reasoned explanation supporting the notion that Mr. Smilo’s

[myasthenia gravis] was contributory.” Id. Additionally, Respondent contends it is not clear

who filled out the death certificate “or how the cause of death was determined,” when in

comparison, the medical records “list only liver failure from HCC as his cause of death, and do

not mention [myasthenia gravis].” Id.

Respondent next argues Dr. Small’s and Dr. DeAngelo’s opinions are “vague,”

“speculative” and “implausible,” and “do not describe how Mr. Smilo’s [myasthenia gravis] or

its sequela led, in any medically or scientifically cognizable way, to the liver cancer that caused

his death.” Resp. Response at 18 (emphasis omitted). With regard to Dr. DeAngelo’s argument

that the medication azathioprine advanced Mr. Smilo’s cancer, Respondent notes “Dr. Lancaster

[] explained[] studies have shown that cancer rates detectably increase only for patients who

43

have been on azathioprine for five to 10 years,” and “Mr. Smilo had a large liver mass on a CT

done in November 2016, prior to starting azathioprine, and was only on the medication for

approximately two months.” Id. And given the size of the mass, Dr. Lancaster opined it had

been growing for months prior. Id.

Thus, Respondent concludes Petitioner did not provide evidence that Mr. Smilo’s

myasthenia gravis or its sequelae were both a but-for cause and a substantial factor in bringing

about his death. Resp. Response at 20-21.

3. Analysis

This case presents the novel question of whether a PEG tube insertion for treatment of

dysphagia, caused by Mr. Smilo’s myasthenia gravis, constitutes “surgical intervention” under

the Act. The Vaccine Act does not define the phrase “surgical intervention,” and therefore, the

words will be given their “ordinary, contemporary, common meaning,” unless Congress

expressed some intent that the phrase should have a particular meaning. Leming, 154 Fed. Cl. at

331 (quoting Williams v. Taylor, 529 U.S. 420, 431 (2000)) (citing Niz-Chavez v. Garland, 141

S. Ct. 1474 (2021)).

As explained by Chief Judge Kaplan in Leming, this statutory provision was added to the

Vaccine Act in 2000 to provide for a new category of petitioners to be entitled to compensation.

Leming, 154 Fed. Cl. at 332. The pre-2000 Act allowed compensation for those injuries that

caused death or lasted six months or longer. Id. In 2000, this additional provision was added,

allowing compensation to petitioners who had a vaccine injury that “resulted in inpatient

hospitalization and surgical intervention.” Id.

In 2000, the year the Act was amended, the definition of the word “surgery” in Dorland’s

Illustrated Medical Dictionary (“Dorland’s”) was the same as it is now: “the branch of medicine

that treats diseases, injuries, and deformities by manual or operative methods.” Leming, 154

Fed. Cl. at 332; Surgery, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/

dorland/definition?id=48252 (last visited May 3, 2023). In 2000, and now, operation includes

“any act performed with instruments or by the hands of a surgeon.” Leming, 154 Fed. Cl. at 332;

Operation, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/

definition?id=35203 (last visited May 3, 2023). In Leming, Chief Judge Kaplan also referenced

the definition from the American Medical Association (“AMA”), which defines surgery as that

performed by a licensed physician “for the purpose of structurally altering the human body by

the incision or destruction of tissues.” Leming, 154 Fed. Cl. at 332 (quoting Surgery, Am. Med.

Ass’n Pol’y Finder, https://policysearch.amaassn.org/policyfinder/detail/surgery? uri=%2FAMA

Doc%2FHOD.xml-0-4317.xml (last revised April 2007)). The AMA statement further provides

that surgery is “the diagnostic or therapeutic treatment of conditions or disease processes by any

instruments causing localized alteration or transposition of live human tissue which include

lasers, . . . scalpels, probes, and needles.” Id. (quoting Surgery, Am. Med. Ass’n Pol’y Finder,

https://policysearch.amaassn.org/policyfinder/detail/surgery? uri=%2FAMADoc%2FHOD.xml-

0-4317.xml (last revised April 2007)).

44

The facts here establish that Mr. Smilo underwent two PEG tube insertions, during two

different hospitalizations. The first operation was January 3, 2017, during Mr. Smilo’s initial

hospitalization for myasthenia gravis. Mr. Smilo’s medical records include an “operative report”

for his PEG tube insertion, which establishes that both a surgeon, Dr. Matthews, and a

gastroenterologist, Dr. Klions, were present for the procedure. Pet. Ex. 5a at 273. The name of

the procedure performed was “[EGD] with placement of a gastrostomy tube.” Id. And

gastrostomy is a “surgical creation of an artificial opening into the stomach.” Gastrostomy,

Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/definition?id=

19901 (last visited May 3, 2023).

In addition to the surgeon and gastroenterologist, there was an anesthesiologist, and the

anesthesia type was MAC, and midazolam, lidocaine, and propofol were administered. The

operative note states that “[a]fter adequate sedation” was obtained, an endoscope was placed by

Dr. Klions (gastroenterologist) and “positioned in the midportion” of the stomach, “directed

towards the anterior abdominal wall.” Pet. Ex. 5a at 274. “A polypectomy snare was passed into

the stomach by [Dr. Klions], [and] opened fully . . . .” Id. On the outside of the abdominal wall,

the surgeon, Dr. Matthews, took the following action: “[t]he overlying skin was anesthetized

with lidocaine and 0.5 cm incision 65 was made.” Id. After the abdominal wall was incised by

Dr. Matthews, he introduced a needle with overlying catheter and passed it “through this incision

and into the stomach under visualization with the endoscope.” Id. The gastrostomy tube was

then inserted as described in the operative report. Id. Mr. Smilo was taken to post-anesthesia

care unit. Id. The record indicates that there were no intraoperative complications. Id. “Dr.

Matthews and Dr. Klions were present . . . for the entirety of the procedure.” Id. Anesthesia

postoperative note by Dr. Sadler documented that the patient had “[n]o [a]pparent

[c]omplications” of anesthesia. Id. at 284.

Mr. Smilo underwent another PEG tube insertion during his last hospitalization. On

April 4, 2017, Mr. Smilo underwent PEG replacement because his first PEG tube had become

dislodged. The procedure was performed by surgeon Dr. Rabinovitz and gastroenterologist Dr.

Das. 66 The procedure was performed under MAC. The operative note verified that the former

PEG tube was misplaced, stating that “[t]here was evidence of a gastrostomy with no G-tube

present in the gastric body.” Pet. Ex. 16a at 91. The surgeon “create[ed] a new tract for G-tube

placement” at a different site in the abdominal wall into the stomach. Id. A “trocar needle was

introduced into the abdominal wall and into the stomach under direct endoscopic view,” and a G-

tube was placed. Id. “The old G-tube was removed[,] and a dressing placed at the site.” Id. at

92.

Using the definitions described above, both PEG tube insertions qualify as “surgery.”

They were both performed by surgeons, described as operations, and operative reports were

65

The operative note does not state what instrument was used to make this incision into the

stomach. Presumably, however, a scalpel or similar instrument was used.

66

Mr. Smilo also underwent an ERCP with placement of two stents at the same time. That

procedure is not discussed here.

45

prepared for both procedures. In both procedures, an incision was made on the outside of the

abdominal wall into the stomach, and instruments, including scalpels and/or needles were used to

incise the skin and stomach. Thus, the undersigned finds that Mr. Smilo underwent two surgical

procedures, as contemplated by the Act.

The second part of the question is whether the two PEG tube surgeries constituted

“interventions” under the Act. The current Dorland’s definition and the 2000 Dorland’s

definition of “intervention” is “the act or fact of interfering so as to modify,” and “specifically,

any measure whose purpose is to improve health or to alter the course of a disease.”

Intervention, Dorland’s Med. Dictionary Online, https://www.dorlandsonline.com/dorland/

definition?id=25701 (last visited May 3, 2023); Leming, 154 Fed. Cl. at 333.

Regarding the question of whether the procedure constituted an “intervention” for

treatment of Mr. Smilo’s myasthenia gravis, the following facts are relevant. The literature

establishes that the “hallmark” of myasthenia gravis is “muscle weakness that worsens after

periods of activity and improves after periods of rest.” Pet. Ex. 12 at 1. “Certain muscles such

as those that control eye and eyelid movement, facial expression, chewing, talking, and

swallowing are often . . . involved in the disorder.” Id. Dysphagia, or difficulty swallowing, is a

symptom of the disease. Id. Mr. Smilo reported a history of difficulty swallowing when he

presented to neurologist Dr. Catalano on December 12, 2016. Pet. Ex. 6 at 12. Dr. Catalano’s

neurological examination revealed “severe dysphagia.” Id. at 13. Mr. Smilo’s condition

worsened, and he was hospitalized on December 22, 2016. Pet. Ex. 5a at 109, 127, 137. During

his hospitalization, his dysphagia did not improve, and he had a PEG tube inserted for

“progressive dysphagia. He failed swallow evaluation and modified barium swallow and had

aspiration and penetration.” Id. at 113, 125. His discharge note states, “Dysphagia. The patient

had a PEG tube placed. This is all secondary to his myasthenia gravis.” Id. at 125.

The records establish that Mr. Smilo’s dysphagia was caused by his myasthenia gravis.

The PEG tube was inserted to treat his dysphagia (inability to swallow) due to the weakness of

the relevant muscles caused by his myasthenia gravis. As such, the two PEG tube surgeries were

measures designed to improve Mr. Smilo’s health, by allowing him to eat and receive

medications for his illness. Fundamentally, the PEG tube was an intervention for his dysphagia,

and his dysphagia was directly caused by myasthenia gravis. Therefore, the undersigned finds

that the two PEG tube procedures which Mr. Smilo underwent constituted “surgical

interventions,” pursuant the Vaccine Act. These “surgical interventions” also resulted in

inpatient hospitalizations” pursuant to the Vaccine Act. Thus, Petitioner has satisfied the

severity requirement of the Act.

Because the undersigned finds Petitioner has satisfied the “resulted in inpatient

hospitalization and surgical intervention” requirement, the undersigned does not reach the second

issue of whether Mr. Smilo’s myasthenia gravis “was a significant contributing fact in bringing

about [his] death,” so as to satisfy the severity requirement of the Vaccine Act.

46

C. Significant Aggravation

1. Loving Factor 1: What Was Mr. Smilo’s Condition Prior to

Administration of the Vaccine?

The first step in the Loving test is to determine Mr. Smilo’s condition prior to the

vaccination he received on October 17, 2016. Prior to vaccination, Mr. Smilo had a history of

hypertension, low back pain, and esophageal reflux. In May 2016, he was seen by Dr. Gavin for

treatment of malaise, cough, nasal congestion, and fever, and Dr. Gavin diagnosed an upper

respiratory infection. Mr. Smilo saw Dr. Gavin again on August 22, 2016, complaining of

dysphagia, hoarseness, and cough. Dr. Gavin ordered an EGD. Approximately one week later,

on September 1, Mr. Smilo was seen by Dr. Mejia for low back pain and complained of trouble

with swallowing. He returned to see Dr. Mejia on September 26, 2016 for low back pain and

reported hoarseness and pain on swallowing.

In addition to the records summarized, post-vaccination records refer to relevant events

that occurred prior to vaccination. Approximately one month after vaccination, on November

17, 2016, Mr. Smilo was seen by Dr. Floyd. Her note documents that he reported ptosis of his

right eye that began three months before the visit. The same day, Mr. Smilo was seen in the ED

for complaints of slurred speech and right side eye droop. Triage Nurse Jellison documented that

Mr. Smilo reported problems with his right eye for months. Also, while in the ED, Mr. Smilo

was seen by Dr. Goebel, who noted that Mr. Smilo noticed his right eyelid drooping three

months before.

The undersigned finds, consistent with her onset ruling, that the onset of Mr. Smilo’s

myasthenia gravis was before vaccination, and that he had right eyelid drooping, trouble

swallowing, hypertension, low back pain, and esophageal reflux prior to vaccination. While he

had not yet been diagnosed with myasthenia gravis, he did have symptoms of the illness.

2. Loving Factor 2: What Is Mr. Smilo’s Current Condition (or His

Condition Following the Vaccination, If Also Pertinent)?

The second part of the Loving test is to discuss “the person’s current condition (or

condition following the vaccination if that is also pertinent).” Loving, 86 Fed. Cl. at 144. Here,

Mr. Smilo’s condition following vaccination is most pertinent.

Approximately one month after vaccination, on November 17, 2016, Mr. Smilo was seen

by Dr. Floyd, who documented that he had ptosis and slurred speech. Diagnostic workup

ultimately revealed a diagnosis of myasthenia gravis. On December 22, 2016, his condition

worsened, requiring hospitalization and PEG tube placement. After treatment and discharge, he

remained stable until March 2017, when he was diagnosed with liver cancer.

47

3. Loving Factor 3: Does Mr. Smilo’s Current Condition (or Condition

After Vaccination) Constitute a “Significant Aggravation” of His

Condition Prior to Vaccination?

The next factor of the Loving test is to determine whether there is a “significant

aggravation” of Mr. Smilo’s condition by comparing his condition before vaccination to his

condition after vaccination. The statute defines “significant aggravation” as “any change for the

worse in a pre-existing condition which results in markedly greater disability, pain, or illness

accompanied by substantial deterioration in health.” § 33(4). Using this definition, the

undersigned finds that, based on the facts and circumstances here, Mr. Smilo had a significant

aggravation of his underlying myasthenia gravis which progressed over time as described in the

medical records, within the month after vaccination. Thus, Petitioner meets the criteria of

Loving Factor Three.

4. Loving Factor Four/Althen Prong One: Medical Theory of Causation

The fourth Loving factor has its origins in Althen Prong One, and Petitioner must set

forth a medical theory explaining how the received vaccine could have caused the sustained

injury. See Andreu, 569 F.3d at 1379; Pafford, 451 F.3d at 1355-56. Petitioner’s theory of

causation need not be medically or scientifically certain, but it must be informed by a “sound and

reliable” medical or scientific explanation. Boatmon, 941 F.3d at 1359; see also Knudsen, 35

F.3d at 548; Veryzer v. Sec’y of Health & Hum. Servs., 98 Fed. Cl. 214, 223 (2011) (noting that

special masters are bound by both § 13(b)(1) and Vaccine Rule 8(b)(1) to consider only evidence

that is both “relevant” and “reliable”). If Petitioner relies upon a medical opinion to support her

theory, the basis for the opinion and the reliability of that basis must be considered in the

determination of how much weight to afford the offered opinion. See Broekelschen v. Sec’y of

Health & Hum. Servs., 618 F.3d 1339, 1347 (Fed. Cir. 2010) (“The special master’s decision

often times is based on the credibility of the experts and the relative persuasiveness of their

competing theories.”); Perreira v. Sec’y of Health & Hum. Servs., 33 F.3d 1375, 1377 n.6 (Fed.

Cir. 1994) (stating that an “expert opinion is no better than the soundness of the reasons

supporting it” (citing Fehrs v. United States, 620 F.2d 255, 265 (Ct. Cl. 1980))).

The undersigned finds Petitioner has failed to establish a sound and reliable medical

theory for how the flu vaccination can cause significant aggravation of myasthenia gravis by

preponderant evidence for the reasons discussed below.

Both Dr. Small and Dr. DeAngelo embraced molecular mimicry as the most common

causal theory used to explain how infections or vaccines cause autoimmune illnesses. And they

cite medical literature that discussed molecular mimicry in general terms in the context of

infections and vaccines. None of the articles cited, however, establish that molecular mimicry

has been posited as a causal mechanism for how the flu vaccine could cause myasthenia gravis.

For example, Dr. DeAngelo discussed the Schwimmbeck et al. paper. But Schwimmbeck et al.

reported a homologous protein between an AChR epitope and a herpes simplex virus

glycoprotein. Dr. DeAngelo did not offer any explanation of how these findings could be

extended to the flu vaccine.

48

Opining that molecular mimicry is a causal theory, without more, is insufficient. See,

e.g., McKown v. Sec’y of Health & Hum. Servs., No. 15-1451V, 2019 WL 4072113, at *50

(Fed. Cl. Spec. Mstr. July 15, 2019) (explaining that “merely chanting the magic words

‘molecular mimicry’ in a Vaccine Act case does not render a causation theory scientifically

reliable, absent additional evidence specifically tying the mechanism to the injury and/or vaccine

in question” (emphasis omitted)); Johnson v. Sec’y of Health & Hum. Servs., No. 14-254V, 2018

WL 2051760, at *26 (Fed. Cl. Spec. Mstr. Mar. 23, 2018) (“Petitioners cannot simply invoke the

concept of molecular mimicry and call it a day. Rather, they need to offer reliable and

persuasive medical or scientific evidence of some kind (whether expert testimony or literature) . .

. .” (internal citations omitted) (emphasis omitted)); Mattus-Long v. Sec’y of Health & Hum.

Servs., No. 15-113V, 2022 WL 4242140, at *27 (Fed. Cl. Spec. Mstr. Aug. 31, 2022) (noting

“the mere mention of molecular mimicry is not a ‘get out of jail free card’ in the Program,

entitling claimants to compensation, merely because it has scientific reliability as a general

matter”); Sheets v. Sec’y of Health & Hum. Servs., No. 16-1173V, 2019 WL 2296212, at *17

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