United States

Background
Antisynthetase syndrome is a rare idiopathic inflammatory myopathy characterized by myositis, interstitial lung disease (ILD), arthritis, Raynaud’s phenomenon, mechanic’s hands, and antibodies against aminoacyl-transfer RNA synthetase, most commonly anti-Jo1 antibody.

Case Presentation
A 36-year-old Hispanic female with no known past medical history presented to the emergency department for 1 week history of left calf pain. She was diagnosed with unprovoked left popliteal vein thrombosis and was discharged on rivaroxaban. She returned the following day for dyspnea and chest pain. She had stable vital signs with adequate oxygenation at room air. Lung auscultation revealed clear breath sounds. Bloodwork showed mild leukocytosis and elevated CK, AST, ALT, and LDH. CT pulmonary angiogram (CTPA) was negative for pulmonary embolism but revealed large infiltrates in bilateral lower lung fields with small bilateral pleural effusions. Ground-glass infiltrates on bilateral upper and lower lobes were seen on high resolution chest CT. Infectious workup for pneumonia was negative. Further questioning revealed a history of two first trimester miscarriages, eczematous skin lesions, and bilateral knee pain. Rheumatologic workup was pertinent for elevated ESR and CRP and positive anti-Ro antibody. ANA, anti-dsDNA, anti-Scl-70, anti-RNP, anti-Smith, anti-cardiolipin, B2-glycoprotein, and lupus anticoagulant were negative. She was started on warfarin for possible antiphospholipid syndrome and steroids for ILD. Four months later, she had worsening dyspnea along with fever and proximal muscle weakness in bilateral lower extremities requiring hospital readmission. CTPA showed progression of bilateral upper and lower lobe ground-glass infiltrates. EMG-NCV was normal. Lung biopsy showed interstitial fibrosis and muscle biopsy of the left vastus lateralis revealed necrotizing autoimmune myopathy. Further rheumatologic workup was significant for positive IgM anticardiolipin and anti-PL-7 antibody but negative anti-Jo1 antibody. Based on the finding of ILD, myositis, and positive anti-PL-7 antibody, a diagnosis of antisynthetase syndrome was made. She continued steroid therapy and started mycophenolate. She had either inadequate control or experienced side effects of the various immunosuppressants. She had tuberculosis while on mycophenolate, myositis flares while on azathioprine, and rhabdomyolysis while on tacrolimus. Her course was complicated by cardiac myositis, and she received intravenous immunoglobulin and rituximab. She was stable on discharge with plans for further infusion, but she died a few weeks later from respiratory failure.

Discussion
Diagnosis of antisynthetase syndrome is based on clinical features and presence of aminoacyl-transfer RNA synthetase antibody, and treatment consists of immunosuppressive therapy. This case illustrates the complexity of diagnosis, often requiring a multi-disciplinary approach, and the difficulty to control symptoms.

2023 AMA Research Challenge

Anti-PL-7 Antibody Positive Antisynthetase Syndrome

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Background
Systemic lupus erythematosus (SLE) is a chronic, multi-systemic autoimmune disorder that presents in a myriad of ways. However, lupus enteritis is a rare initial manifestation. 

Case Presentation
A 30-year-old female with PMH DM2 and obesity presented with periumbilical pain for one day associated with nausea, NBNB vomiting, and fatigue. She denied rashes, skin changes, fever, arthralgias, oral ulcers or hair loss. On examination, temperature 97.7°F, BP 138/69, HR 121, RR 22, and O2 saturation 99% on room air; bowel sounds were normal and there was diffuse abdominal tenderness and distension without rebound/guarding. Notable labs included creatinine 1.2 and a urinalysis showing protein 300, RBCs (6-10), and protein/creatinine ratio 2304. A CT abdomen revealed moderate ascites and an approximately 42 cm segment of moderate small bowel wall thickening, predominately of the proximal jejunum, concerning for infectious or inflammatory enteritis. Ascitic fluid studies revealed SAAG <1.1 g/dL. A subsequent MRI abdomen showed possible mid-small bowel obstruction and targetoid mucosal and serosal enhancement. The obstruction was managed conservatively with NGT placement; however, her abdominal pain persisted even though she had bowel movements and had no radiographic worsening of the obstruction. During the hospitalization, her renal function did not improve; an autoimmune work-up revealed positive ANA, dsDNA, anti-smith Ab, RNP Ab, chromatin Ab, ribo protein IgG, and SM RNP Ab; C3 and C4 complement levels and serum albumin were low. She was transferred to a tertiary care center and a kidney biopsy revealed Class III lupus nephritis. She was started on pulse-dose steroids and hydroxychloroquine. She improved clinically, her renal function improved and she was discharged home on azathioprine, hydroxychloroquine and prednisone.

Discussion
SLE can affect numerous systems but rarely involves the gastrointestinal system as an initial manifestation. Lupus enteritis is only present in about 0.2 – 5.8% of cases with SLE. It is thought to be related to immune complex deposition and complement activation leading to submucosal bowel wall edema and mostly affects the Jejunum and the Ileum. The clinical presentation is often nonspecific, however frequent complaints include abdominal pain, nausea, and vomiting. CT abdomen/pelvis is the diagnostic modality of choice as pathology is low yield. Common imaging features include Target sign, Combs sign, Mesenteric fat stranding and ascites. Due to its rarity, there are no established guidelines for management, however prior case reports have demonstrated a positive response to steroids.



Lupus Enteritis: An Uncommon Manifestation of Systemic Lupus Erythematosus that Coalesced with Cryptogenic Lupus Nephritis

Background
Carcinoid tumors are masses originating from neuroendocrine cells and are one of the rarest forms of endocrine cancer. Minimal literature exists regarding neuroendocrine tumors arising from the mediastinum, let alone the thymus. This is likely secondary to its rarity, with a reported incidence of 0.2 per million in the United States.
Case Presentation
When diagnosing a neuroendocrine tumor, it is crucial to distinguish the combined neuroendocrine and epithelial characteristics of the neoplasm, acknowledge its potential aggressiveness, and establish additional markers for prognosis and prediction. In the following review, we present a case of a 64-year-old male with an incidental finding of an atypical thymic neuroendocrine tumor. A radical robotic-assisted thymectomy was performed, and adjuvant radiotherapy was administered. 
Discussion
Atypical thymic neuroendocrine tumors remain a niche disease, presenting a unique challenge due to rarity, diverse characteristics, and aggressiveness. Though lacking consensus or best-practice guidelines, surgery is considered the most curative treatment modality. Proving the variability of this type of tumor, however, radiation therapy has had unclear and inconsistent effects on long-term survival, either enhancing clinical outcomes or failing to improve 5-year survival rates. Overall, survival rates for thymic neuroendocrine tumors are lower than those of the gastrointestinal tract, highlighting the need for better therapeutic strategies to maintain the highest level of care for such patients.

Thymic Atypical Carcinoid Tumors vs. Gastrointestinal Neuroendocrine Tumors - 
Are They Really the Same Disease?

Xp11 translocation renal cell carcinomas (RCC) are a category of RCCs
that involve translocations of the chromosome Xp11.2, which is
responsible for generating fusions of transcription factor E3 (TFE3).
These malignancies encompass the most prevalent type of RCC in the
pediatric population, while in adults, Xp11 RCCs account for merely 1-
4% of renal malignancies.
We detail the case of a 68-year-old male who presented to the
emergency department after a ground-level fall with a small forehead
laceration. As part of his work-up, a non-contrast CT abdomen/pelvis
was obtained, on which a 3.9 x 4.5cm left posterior mid-pole renal mass
was noted, suspicious for an RCC. Further workup confirmed an
enhancing posterior left renal mass with no evidence of metastatic
disease. Histopathological and genetic analysis of the extirpated mass
was notable for a Xp11 translocation RCC, pT1bNXMX Fuhrman Grade 2,
with negative margins. Considering the patient had no local invasion or
metastasis, he was discharged and scheduled for surveillance imaging.
Overall, Xp11.2 RCCs in the elderly population are uncommon. Genetic
and IHC analysis is essential in providing accurate and timely diagnoses
of RCCs of this subtype. Since prognosis of this neoplasm in adults is
worse than in pediatric patients, awareness of adequate interventions
and diagnostic tools is of the utmost importance in order to improve
patient outcomes.

68 Year-Old Male with Rare Xp11 Translocation Renal Cell Carcinoma


Background: Testicular infarction is a rare complication of epididymitis. We present a case of testicular infarction to highlight this complication and the role of ultrasound in aiding diagnosis to guide management.

Case Presentation: 26-year-old male, with recent admission for left epididymitis secondary to Multiple Drug Resistant Enterobacter, presented to the emergency department with a two-day history of progressively worsening left scrotal pain and swelling. Physical examination revealed left scrotal erythema and tenderness. Scrotal ultrasound demonstrated asymmetric enlargement and heterogeneous appearance of the left testicle consistent with left scrotal edema. The left testicle showed peripheral hypervascularity without intrinsic flow on color and spectral Doppler interrogation compatible with testicular infarction. In contrast, the right testicle was homogenous and with normal arterial and venous spectral Doppler flow. Management included intravenous antibiotic and urology consultation with subsequent partial orchiectomy. Patient’s hospital course was complicated by wound dehiscence and residual necrotic tissue requiring scrotal debridement and washout. After transition to oral antibiotics, he was discharged with outpatient follow-up with urology.

Discussion: Ultrasound with color flow Doppler is the primary method to diagnose testicular infarction secondary to epididymitis. Characteristics of testicular infarction include asymmetrically decreased or absent intrinsic testicular blood flow with or without increased peripheral flow. Although understanding of the pathophysiology of testicular infarction is evolving, arterial and venous insufficiency are suspected. Risk of global testicular infarction is low due to the testes receiving blood supply from the testicular, the deferential and cremasteric arteries. Persistent clinical symptoms and worsening imaging findings can warrant surgical intervention. In addition to spectral and color doppler, there is expanding utilization of contrast- enhanced sonography (CEUS) to increase sensitivity for testicular infarction. Testicular infarction is a rare but important diagnosis to consider in the setting of epididymitis that has management implications to prevent morbidity.

Treatment Failure of Epididymitis leads to Testicular Infarction

Background: Myasthenia gravis, the most common autoimmune disease affecting the neuromuscular junction, is characterized by generalized muscle weakness. Myasthenia is easily treated, yet social determinants of health can complicate a patient’s access to treatment, prolonging symptoms and increasing patient suffering. Further, residents of rural Maine struggle with healthcare access, as 40% of Mainers live in rural areas and 6% of Mainers are uninsured. 

Case Presentation: A 29-year-old female presented to our hospital’s emergency department from her neurologist’s office. She presented with four months of neck and limb weakness and dysphagia; these symptoms worsened throughout the day. She recently had left her job, as she could no longer perform her duties due to weakness. A resident of rural Maine without health insurance who did not qualify for Medicaid, this patient had not seen a primary care provider (PCP) in five years. She was previously evaluated in an urgent care for similar symptoms and was advised to consult a PCP for further work-up. It took two months for the patient to secure a PCP; she was referred to a neurologist who immediately sent her to the emergency department.

On examination, the patient’s strength was globally 3/5. She was hyporeflexive. She ambulated with a walker. A workup for a neuromuscular syndrome was started. A chest CT did not show a thymoma. The patient was admitted to the hospital, where she was seen by neurology and started on pyridostigmine; she demonstrated immediate improvement. She was discharged one day later with a diagnosis of myasthenia and inflammatory motor neuropathy.

On follow-up with her neurologist one month later, the patient reported mild improvement with pyridostigmine. IV immunoglobulin (IVIG) therapy was ordered to treat her motor neuropathy. However, the patient was still unable to secure insurance, and IVIG therapy was delayed two months. Three months post-discharge, the patient secured insurance and began treatment with IVIG infusions. 

Discussion: The most salient aspect of this case is the patient’s social determinants of health – specifically lack of health care access. This case highlights the disparities that exist for underinsured adults and the great need for PCPs, especially in rural areas. Further, myasthenia is easily treated, yet the patient’s delay in treatment played an enormous impact on her physical and social wellbeing. This case serves to underline the consequences of limited PCP availability and insurance access which prolongs physical and social suffering for conditions with clear treatment, such as the myasthenia demonstrated in this case. 


Myasthenia Gravis Complicated by Lack of Healthcare Access in Rural Maine

Background:
Amiodarone-induced thyrotoxicosis (AIT) is one of the many side effects of the antiarrhythmic amiodarone. It can manifest in two forms: type 1 and type 2. Type 1 AIT occurs in patients with preexisting thyroid disease and is caused by excess thyroid hormone synthesis due to amiodarone’s high iodine content. Type 2 AIT is a destructive thyroiditis resulting from amiodarone’s direct toxicity on the thyroid gland causing the release thyroid hormone. Differentiating between these two is challenging due to overlapping clinical features and laboratory findings. However, it may be advantageous to differentiate between type 1 and type 2 AIT as the treatment approaches vary. A collaborative approach involving endocrinology, cardiology and the primary team is essential for accurate diagnosis and timely management.

Case Presentation:
A 67-year-old male with a past medical history of hypertension, hyperlipidemia, atrial fibrillation, coronary artery disease status post coronary bypass, and plaque psoriasis presented to our ER complaining of chest pain during bowel movements. Home medications included apixaban, amiodarone, lisinopril, carvedilol, atorvastatin, and isosorbide mononitrate. He was accepted to the ICU due refractory atrial fibrillation with rapid ventricular rate (A-fib with RVR).

Discussion:
The diagnosis was AIT causing refractory Afib w/RVR, however uncertainty remains regarding the type of AIT and complicating management. We suspected type II AIT as the patient lacks Graves’ disease or nodular goiter. Unfortunately, guidelines providing a clear distinction between type I and type II are limited, contributing to the lack of standard treatment approaches.
Clinical criteria used to differentiate between type I and type II AIT include timing, onset, underlying thyroid disease, thyroid hormone levels, and thyroid scintigraphy. There is also color flow doppler sonography (CFDS) which is a real time technique that depicts intrathyroidal blood flow giving physician information on thyroid morphology and hyperfunction. While these tools provide insight it is important to note that these criteria may overlap, and atypical presentations make the differentiation challenging. One aspect of contention revolves around the continuation or discontinuation of amiodarone. Some clinicians argue that if the type of AIT remains uncertain, continuing amiodarone for rhythm and rate control in atrial fibrillation does not significantly prolong the patient’s hospital stay. Conversely, others advocate for discontinuing amiodarone unless there is a life-threatening ventricular arrhythmia. Establishing a consensus to differentiate the types of AIT would improve treatment approaches and reduce the need for more invasive measures like thyroidectomy.


Amoidarone-induced Thyrotoxicosis (AIT): Subtype Differentiation and Management

Chat Generative Pretrained Transformer (ChatGPT) is a new language model developed to learn and converse interactively with users. Current medical research using ChatGPT has been done through the allopathic lens. Our research project shifts this viewpoint to focus on the Osteopathic holistic beliefs by asking ChatGPT questions about Osteopathic Manipulative Medicine (OMM). This research project will add to ChatGPT's knowledge base and provide physicians with more insight into ChatGPTs abilities.

Analyzing ChatGPT’s Proficiency In Multiple Choice Osteopathic Manipulative Medicine Questions: Insights and Implications

Background
Amphetamines are the first line treatment for ADHD in adults. There are many cardiac pathologies associated with amphetamine use such as hypertension, atrial fibrillation, and cardiomyopathy. A known complication of amphetamine abuse is that it can induce thoracic aortic dissection by facilitating the breakdown of elastin, medial cells, and degeneration of the blood vessel. Another proposed etiology for the association of amphetamine use and aortic dissection is hypertensive-mediated aortic dissection secondary to amphetamine use. Marfan’s syndrome is a congenital defect in fibrillin 1 which leads to impaired elastin formation. The leading cause of death in patients with Marfan’s syndrome is aortic pathology, specifically aortic dissection. The association between Marfan’s syndrome and amphetamine use is something not well described in the literature. 
Case Presentation
A 21-year-old man with a history of ADHD and Marfan’s syndrome presents to his primary care physician requesting medications to help him “focus” and “concentrate”. He had no other complaints and his physical exam showed a tall and lanky man, with arms disproportionally longer than his body. No cardiac abnormalities were heard on auscultation and no cataracts were visible on fundoscopy. His physician reviewed his previous EKG from three months prior and administered another EKG in clinic. Both EKG’s showed sinus rhythm with no indications of any heart defects or atrial fibrillations. Echocardiography from his cardiologist showed no aortic root dilation or cardiomyopathy. The patient was prescribed amphetamines, informed of the potential risks, and told to follow up in 4 weeks. 
Discussion
Marfan’s syndrome presents with variable expressivity, with some phenotypes being milder than others. This patient presented with a marfanoid body habitus but showed no cardiovascular or ocular abnormalities. Physicians should consider the risks associated with prescribing amphetamines for ADHD in patients with Marfan’s Syndrome. The literature only describes one reported case of amphetamine induced aortic dissection in a Marfan’s patient. Other papers claim undiagnosed Marfan Syndrome to be the culprit as to why there hasn’t been a clear established relationship between the two, pushing that every atypical aortic dissection in young people should be biopsied for connective tissue diseases. Nevertheless, reason compels physicians to complete a full cardiac workup of patients with Marfan’s syndrome to evaluate for any cardiac or aortic manifestation of disease that would push them to try a safer alternative for their patient. 


Aortic Complications to Consider in the Management of ADHD 
in Marfan’s Patients

This case details a unique fatal outcome of myocarditis in a 17-year-old Black male. The young patient initially displayed symptoms resembling stomach flu. A rapid decline in his health led to sudden death. Postmortem findings and CDC evaluation revealed ischemic myocarditis as the cause. Two positive post-mortem COVID tests suggest emphasizing the need for broader diagnostic perspectives, vigilance in monitoring symptom evolution, and understanding of COVID-19's varied impacts on the pediatric population


Fatal Case of Myocarditis in a 17-Year-Old Black Male with COVID-19

Background. Cocaine abuse is a major worldwide health problem with an estimated 5 million users in the USA. Crack cocaine inhalation causes serious pulmonary complications, which may progress to respiratory failure, leading to in-hospital mortality ranging from 20% to 100% [1]. Pulmonary complications include: diffuse alveolar damage and hemorrhagic alveolitis, pulmonary edema, eosinophilic pneumonia, foreign body granulomas, cocaine related pulmonary infection, obliterative bronchiolitis, asthma, pneumothorax, thromboembolic disease and persistent gas-exchange abnormalities. Respiratory manifestations are nonspecific and include shortness of breath, fever, cough, wheezing, hemoptysis, and chest pains. 
Case Presentation. A 42-year-old male was found unresponsive on the street with a crack pipe on him. He had pinpoint pupils and was breathing inadequately with respiratory rate (RR) of 7-8 per minute. After he was given naloxone, he started reacting to noxious stimuli. He was placed on a non-rebreather mask (NRBM) and was transferred to the hospital. In the emergency room, the patient was hypertensive, tachycardic, and desaturating to the 50s, which together with low Glasgow Coma Scale (GCS) prompted intubation and mechanical ventilation with settings of FiO2 100%, VT 460 ml, RR 24, and PEEP 12. The patient became hypotensive, requiring two vasopressors. On a physical exam, a large amount of blood was noted in the endotracheal tube. Initial labs showed pH 7.16, pCO2 59, pO2 53, elevated lactate and neutrophilic leukocytosis. Urine toxicology was positive for cocaine. EKG showed sinus tachycardia. Chest X-ray demonstrated bilateral infiltrates. CT-chest revealed extensive bilateral airspace opacities suggesting ARDS versus diffuse pulmonary hemorrhage. The patient was admitted to ICU for acute hypoxemic hypercapnic respiratory failure, circulatory shock due to ARDS vs diffuse alveolar hemorrhage and septic shock due to aspiration pneumonia. The management included antibiotics, IV fluids, vasopressors and supportive care. During a course of ICU stay for four days, the patient’s needs for vasopressors decreased and mental status improved. On day 4, the patient extubated himself. He was placed on a high flow nasal cannula. His vital signs remained stable, and he was alert and oriented to person, place and time. On repeat chest X-ray, diffuse bilateral airspace opacities decreased in size. Thus, the patient was downgraded to the floor.
Conclusion. The present case highlights pulmonary complications of cocaine use. Clinicians must consider various pulmonary complications in the differential diagnosis of respiratory failure when evaluating critically ill patients with history of cocaine use.


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Anti-PL-7 Antibody Positive Antisynthetase Syndrome

Next from 2023 AMA Research Challenge

Lupus Enteritis: An Uncommon Manifestation of Systemic Lupus Erythematosus that Coalesced with Cryptogenic Lupus Nephritis