# Smilo v. Secretary of Health and Human Services

> United States Court of Federal Claims · June 9, 2023

URL: https://www.frixlaw.com/law-library/cases/9400825

## Case

- **Court:** United States Court of Federal Claims
- **Decided:** June 9, 2023
- **Precedential status:** Published
- **Opinion:** Opinion
- **Judges:** Nora Beth Dorsey
- **Cited by:** 0 later opinions in the Frix Law Library

## Citator (automated)

- No negative treatment found by the automated citator. That is not the same as a confirmation that the case is good law; read the citing cases.
- Full citator and citing cases: https://www.frixlaw.com/law-library/cases/9400825

## How later opinions describe it (automated extraction)

- noting that “clear, cogent, and consistent testimony can overcome such missing or contradictory medical records”
- noting that “close calls” are resolved in Petitioner’s favor
- 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”

## Opinion text

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

[Text truncated at 120,000 characters. The full text is on the page linked above.]

---

Source: Frix Law Library, https://www.frixlaw.com/law-library/cases/9400825. Public record. Not legal advice.