AMOPS 2021 Research Symposium

Congenital cytomegalovirus infection (cCMV) is the most common congenital infection. A majority are asymptomatic at birth. However, symptomatic cCMV can be devastating for multiple organs including the liver. A term female was born with a purpuric rash and hepatosplenomegaly. Prenatal history included maternal fever with elevated LFTs at 6-weeks-gestation with later serology positive for CMV. Neonatal laboratory studies were significant for elevated LFTs, thrombocytopenia, and a positive urine PCR for CMV. Ganciclovir was started within 24 hours and continued on it for five days before transitioning to valgancyclovir. She remained on valgancyclovir and had down trending labs by 2.5 months of life. At 4 months old she had acute worsening of hepatitis with cholestasis that was identified during routine follow-up that quickly progressed into end-stage liver disease. She continued to demonstrate CMV viremia without any other known etiologies. Patient received her liver transplant at 4.5 month of age and is doing well in the post-operative period. The native liver appeared dense and cholestatic with patchy lymphocytic infiltration. Liver and gallbladder architecture were normal. Pathological features were consistent with history of cCMV infection, although CMV immunostaining was negative. Hepatitis is a known complication of cCMV. Risk factors for severe cases of cCMV are reported in premature infants and those born to mothers with a primary CMV infection. Our case demonstrated progression to liver failure from a cholestatic hepatitis in a term infant who received parenteral and longer term oral antiviral therapy. Consistent with other patient reports, initial therapy appeared successful. However, our patient did not follow the typical course and had prominent cholestasis. Patients with cCMV with hepatitis and cholestasis may represent a subgroup at higher risk of disease progression and possible hepatic failure. Cholestasis may be a consideration for longer ganciclovir treatment before transitioning and closer follow up.

Erica M. Grimm DO

Madigan Army Medical Center, Department of Pediatrics

Introduction It is well known that infectious mononucleosis (IM) is caused by the Epstein-Barr Virus (EBV) and classically presents with the triad of fever, tonsillar pharyngitis and lymphadenopathy. Often accompanying the classic triad are general malaise, sore throat, fatigue, hepatosplenomegaly, myalgias and rash. A less common associated symptom, however is periorbital edema, also known as Hoagland sign. Case Description A ten year old female presented to clinic for three days of swelling around both eyes, in the context of worsening fatigue, malaise, congestion, cough and intermittent fevers. On physical exam, the patient was afebrile, tachycardic, and minimally ambulatory. Eyes were without injection or discharge, however marked periorbital edema was present bilaterally. She also had significant anterior, asymmetric, non-tender cervical lymphadenopathy and enlarged tonsils (4+) with exudates bilaterally. The spleen was palpated 1cm below the costal margin. Lab results were significant for elevated atypical lymphocytosis, absolute lymphocytes, absolute monocytes, AST and ALT. Despite a negative heterophile antibody test, IM was suspected and she was ultimately admitted for supportive care. VCA IgM/IgG testing was performed and later resulted positive, confirming IM as the cause of the patient’s presentation. Her periorbital edema had completely resolved within six days. Discussion This case highlights a less common but striking presentation of infectious mononucleosis. While this manifestation is rarely an early presentation of IM, it has been a reported feature of IM patients in up to 50% of cases in some studies. Hoagland sign, when present, typically occurs early and is transient; it is not usually associated with eyelid tenderness or conjunctivitis. While the pathophysiology is not well understood, it is presumed that lymphocytic infiltration and nasopharyngeal viral replication may contribute. The early recognition of Hoagland sign has the potential to allow a straightforward diagnosis and appropriate subsequent management.

Marie Noah DO

Madigan Army Medical Center

Parsonage-Turner Syndrome Presenting as Severe Acute on Chronic Shoulder Pain in the Setting of Shoulder Arthritis David M. Smith, OMS-III; Patrick T. Kiernan, OMS-IV; Yu D. Cheng, MD, PhD; Anette G. Gawelko, DO Introduction: Parsonage-Turner Syndrome, idiopathic brachial plexopathy, is a rare disorder characterized by acute onset severe shoulder pain followed by progressive neurological deficits. The precise etiology is unknown, but it is associated with many clinical scenarios including infection, surgery, trauma, and postvaccination. Case Description: ​A 78-year-old diabetic male was admitted for sepsis secondary to osteomyelitis of the left midfoot. He had a history of left shoulder arthritis with baseline chronic, mild, achy shoulder pain. Two days after admission, the patient complained of new onset left shoulder pain that was severe, constant, sharp, and would awaken him from sleep. Pertinent exam findings included 4/5 strength in the deltoid and supraspinatus. Radiographs demonstrated glenohumeral and acromioclavicular joint space narrowing and osteophyte formation consistent with osteoarthritis. MRI showed severe glenohumeral arthritis, moderate acromioclavicular arthritis, and partial articular-sided tears of the supraspinatus and infraspinatus. A diagnostic intraarticular corticosteroid with lidocaine injection was performed which provided incomplete relief. Given the lack of improvement there was increased suspicion for an extraarticular etiology. A brachial plexus MRI was obtained which demonstrated edema of the C5-C7 nerve roots and denervation edema of the rotator cuff and deltoid consistent with acute brachial neuritis. The patient was started on a two-week course of prednisone to be followed by a two-week taper. Discussion: Parsonage-Turner Syndrome is a rare cause of acute onset severe shoulder pain with an incidence of 1.64 cases per 100,000 people. Differential diagnosis includes more common disorders such as cervical disc disease, adhesive capsulitis, and rotator cuff calcific tendinosis. In addition to characteristic MRI findings described above, electromyography can confirm the diagnosis. EMG evidence of acute denervation in an atypical, patchy distribution (i.e. both peripheral nerve and nerve root involvement) is diagnostic. Treatment includes pain control and oral corticosteroids acutely followed by long-term multidisciplinary rehabilitation. Abstract word count: 296 References (for poster): Feinberg JH, Radecki J. Parsonage-turner syndrome. HSS J. 2010;6(2):199-205. doi:10.1007/s11420-010-9176-x Beghi E, Kurland LT, Mulder DW, Nicolosi A. Brachial plexus neuropathy in the population of Rochester, Minnesota. Ann Neurol. 1985;18:320–323. doi: 10.1002/ana.410180308. Van Eijk, Jeroen JJ, Jan T. Groothuis, and Nens Van Alfen. "Neuralgic amyotrophy: an update on diagnosis, pathophysiology, and treatment." Muscle & nerve 53.3 (2016): 337-350.

David Smith OMS-III

Arizona College of Osteopathic Medicine

Various nutritional influences on the risk of preeclampsia have been studied with inconsistent results. This paper compiles the most notable nutritional factors and hypothesizes the mechanisms thought to be associated with the pathogenesis of preeclampsia. The goal of this research is to determine if varying levels of nutritional factors, via diet, supplementation, or lifestyle changes, can significantly reduce the risk of developing preeclampsia or improve preeclampsia outcomes. In examining vitamin D, calcium, magnesium, zinc, copper, folic acid, exercise, glucose, and overall diet, the research suggests that significant risk protection exists. Indicated supplementations include vitamin D (10-15 µg/day), calcium (> 1 g/day), folic acid (5 mg/day), and exercise (increasing exercise levels correlate with decreasing risk of preeclampsia). Magnesium levels, increasing exercise, and adherence to a Mediterranean diet may be associated with improvement of preeclamptic symptoms. The relationships of copper and zinc to risk or treatment of preeclampsia are inconclusive. This paper recommends more research in this area in order to suggest accessible and affordable lifestyle changes to women, which can combat the contribution of preeclampsia to maternal mortality

Yash Makkapati MS OMS1

New York Institute of Technology College of Osteopathic Medicine at Arkansas State

Background: Cryoablation, the destruction of cells by ultra-low temperatures, has been used to treat benign breast disease and two clinical trials (ACOSOG Z1072 and FROST) have been conducted to determine its utility in invasive breast cancers. The focus of the trials has been the rate of complete tumor ablation with no assessment of immunological responses. We hypothesize that neoantigens released during cryoablation might be sufficient to trigger a robust immune response to prevent and/or reduce spread and relapse of breast cancers. In this pilot study we 1) evaluated biopsy material, cryoablated specimens and axillary lymph nodes from patients with cancers smaller than 2cm enrolled in the ACOSOG Z1072 trial at Lankenau Medical Center [N=18] and 2) assessed immune responses and effects on metastases formation in the classical mouse mammary tumor model 4T1 in immune competent Balb/c mice. In both settings responses were compared to patients/mice treated with surgical resection alone.

Methods: After obtaining IRB approval for retrospective analyses of specimens from the ACOSOG Z1072 trial, immunohistochemical staining of surgical specimens was performed. Sections were stained for CD4, CD8, CD20, CD21, and CD1c. In the IACUC approved animal experiments, 4T1 cells were injected orthotopically in the mammary fatpad to initiate tumor growth. Small tumors were treated by cryoablation or surgery alone. Animals were euthanized 7 days post-treatment and tissues were collected to assess cytokine levels and presence of dissociated 4T1 cells. Single-cell suspensions of tumor, tumor-draining lymph node [TDLN], and spleen were tested for secretion of mouse Th1/Th2 cytokines using a bead array and measured by flow cytometry. Possible metastatic spread was assessed by a clonogenic assay using cells from venous blood, lung and brain. Cell suspensions were seeded in growth medium with the selection agent 6-thioguanine, allowing only resistant 4T1 cells to form colonies.

Results: Cryoablation transformed tumors in both patients and mice into a gelatinous mass surrounded by a fibrotic capsule. Sections of tumors from both humans and mice displayed a necrotic core and infiltrating lymphocytes in the microenvironment. The cryoablated human tumors had slightly higher presence of lymphocytes positive for CD8+ compared to CD4+. The inverse relation was observed in non-cryoablated specimens. No significant difference was observed for CD20+ lymphocytes. Tumor-draining lymph nodes from cryoablated patients had an elevated presence of CD20+ B cells compared to patient treated by surgery alone. Follicular dendritic cells (CD21+) were also present at higher numbers in TDLN from cryoablated patients. Animals treated with cryoablation displayed robust increases of Th1 and Th2 cytokines in both spleen and TDLN compared to animals with surgery treatment. In the animals, circulating tumor cells were found prior to treatment, while no 4T1 colonies formed from cell suspensions of lung and brain tissue [N=8]. At end-point, the surgery group had more 4T1 foci formed from lung and brain [mean foci/animaI = 6.25 and 0.75, respectively; N=6] than the cryo group that had 2.25 and 0 foci in lung and brain, respectively [N=8].

Conclusion: Cryoablation of breast cancer lesions can induce stimulatory immune responses in vivo. These immune responses might explain why animals treated with cryoablation, though having circulating tumor cells at the time of treatment, exhibited fewer micro metastatic growths compared to surgery alone. The presence of elevated numbers of CD20+ in TDLN has been associated with improved disease-free survival. All local patients in the clinical trial are currently disease-free (5 to 9-year F/U) which is higher than expected recurrence rate at 15% at 9 years post treatment.

Allison Campoverde OMS-III

Rowan University School of Osteopathic Medicine and Lankenau Institute for Medical Research

This case report describes a patient with COVID-19 pneumonia with superimposed Mycoplasma infection, both of which were diagnosed on CT imaging performed upon initial Emergency Department evaluation, and later confirmed by laboratory studies. This abstract calls for low threshold for CT imaging evaluation of patients with presumed COVID-19 infections, and calls into question a need for additional diagnostic evaluation of SARC-CoV-2 patients, specifically with respect to identification and treatment of bacterial agents that may be responsible for superimposed respiratory processes.

Michael A. Talalaev DO <michael.talalaev@gmail.com>

Larkin Palm Springs Hospital, Miami, FL

According to the American Heart Association (AHA), rates of successful resuscitation after out of hospital cardiac arrest (OHCA) vary across the country. Amongst 132 counties in the United States, the rates of CPR survival to hospital discharge ranges between 3.4%-22.0%, and the rates of CPR survival with functional recovery ranges from 0.8%-20.1%. This large degree of variability between regions has been improved through programs that educate Emergency Medical Service (EMS) departments on ways to improve outcomes through an evidence-based lens. The Medic One EMS department in Seattle and King County, Washington developed a resuscitation academy (RA) that improved cardiac arrest survival from 26% in 2002 to 62% in 2013. In 2015, The New Castle County, Delaware EMS (NCCEMS) department modeled a RA after the Medic One EMS department. This study measured the effect on the number of patients experiencing return of spontaneous circulation (ROSC) and the cerebral performance category (CPC) scores for discharged patients. Data from 599 atraumatic out-of-hospital cardiac arrests (OHCA) was collected from 2009-2019, and 99 cases met Utstein inclusion criteria. Next, the study categorized if at least one RA was implemented prior to these cases to determine the RA’s effect. Implementation of one RA on ROSC outcomes yielded a significant improvement (p = .028), with a small to medium strength of effect (Cramer’s V=0.221); this indicates that the administration of at least one RA had a moderate and significant effect on increasing ROSC in patients suffering from OHCA. Administration of at least one RA did not demonstrate a significant effect on eventual patient outcomes as indicated by discharge CPC score (p = .488). This indicates that there was no statistically significant effect on the cerebral performance of patients who suffered OHCA upon discharge.

Jeffrey Kalczynski OMSIV and Thomas DePietro OMSIV

Philadelphia College of Osteopathic Medicine