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**Abstract:**



2023 AMA Research Challenge

Saccharomyces cerevisiae (Baker’s Yeast) Pneumonia in an Immunocompromised Host

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Background
Shigella is a Gram-negative, facultative anaerobic bacteria that causes a gastrointestinal infection characterized by bloody diarrhea. First-line treatment is azithromycin; however, in the men who have sex with men (MSM) population, Shigella is known for higher rates of azithromycin resistance. Other treatments, including trimethoprim-sulfamethoxazole, fluoroquinolones, and ampicillin, are also increasing in resistance. 

Glucose-6-Phosphate Dehydrogenase (G6PD) is an enzyme that prevents cellular damage from reactive oxygen species (ROS), to which red blood cells are especially susceptible. G6PD-deficiency is an inherited disorder characterized by acute hemolytic anemia after exposure to high levels of ROS from foods and certain antibiotics, including many that are used for treatment of Shigella.

Case Presentation
A healthy 28-year-old male with a history of MSM activity presented to the emergency department (ED) with four days of 15-20 daily episodes of increasingly bloody diarrhea and a recent exposure to a sick contact with similar symptoms. As an Active Duty Sailor, he initially sought care from his ship’s physician who prescribed azithromycin and acetaminophen without relief. In the ED, he was tachycardic and physical exam revealed tenderness of left abdominal quadrants with rebound. Rectal exam showed bright red blood and watery brown stool. Lab work was notable for leukocytosis, acute kidney injury (BUN 40, Cr 3.3), and lactate 2.1. A CT abdomen/pelvis revealed moderate proctocolitis. He reported no known drug allergies, and was given fluids, ciprofloxacin 500 mg, and metronidazole 500 mg for presumed infectious diarrhea. He was admitted to the Internal Medicine Ward, where GI Stool PCR resulted positive for Shigella. Chart review indicated a history of G6PD-deficiency, at which point he was transitioned to ceftriaxone from ciprofloxacin with an Infectious Disease consult. He clinically improved and was discharged home on Augmentin; however his symptoms did not resolve on Augmentin. Culture sensitivities resulted after his discharge, which demonstrated resistance to ampicillin. He was switched to cefpodoxime per Infectious Disease recommendation and recovered fully.

Discussion
This case illustrates the value of complete history gathering in determining a patient’s full spectrum of risk factors. Relevant for this patient was his sexual history and medication intolerances that he did not initially disclose. It also highlights the growing importance of alternative treatment regimens to mitigate the adverse effects of increasing global rates of antibiotic resistance, especially for patients with complex histories and medication intolerances.

Diarrheal Dilemma: G6PD-Deficiency Complicating Treatment of Antibiotic- Resistant Shigella in the MSM Population

The lone star tick (Amblyomma americanum) in the United States spreads diseases such as Ehrlichiosis, Rocky Mountain spotted fever, tularemia, and STARI. Their aggressive biting and covert attachment require immediate removal and avoidance of infested areas. We present a case report of a 28-year-old male entomologist who presented to the emergency department after being bitten by numerous lone star ticks while collecting samples. He experienced skin reactions at the bite sites and was started on doxycycline for prophylaxis. Antihistamines were prescribed, and he was advised to carry an epinephrine auto-injector and avoid allergens. Blood tests showed no abnormalities. Additionally, he developed an alpha-gal allergy from the tick bites, leading to allergies to various foods and environmental factors. This is likely due to the introduction of alpha-gal into the body through the tick bites, leading to an immune response and subsequent allergic reactions. The patient's condition also involves allergies to environmental antigens such as Timothy grass, white oats, and American elm. A personalized dietary plan, avoidance of allergens, and preventive measures against tick bites were recommended. Osteopathic considerations, immunological testing, and referral to an allergist were suggested for further management. He planned to undergo tests for alpha-gal and alpha tryptase but encountered difficulties due to insurance issues. This case highlights the challenges faced by patients in accessing necessary diagnostic tests for tick-related allergies and emphasizes the importance of addressing insurance barriers to ensure appropriate care for individuals at risk. In conclusion, this case highlights the challenges faced by patients in accessing diagnostic tests for tick-related allergies due to insurance issues, underscoring the need to address these barriers to ensure appropriate care for individuals at risk of developing multiple allergies following lone star tick bites.

The Last Bite: Development of Nonspecific Allergic Response After Environmental Trigger

Pott Puffy Tumor is a rare disorder commonly seen in adolescent populations and typically arises as a complication of severe sinusitis, leading to osteomyelitis of the frontal bone and presenting as swelling of the forehead. Herein, we report a case of a 46-year-old male with no significant known medical history presenting with seven months of headache. This case highlights the importance of considering Pott Puffy Tumor as a differential diagnosis in adult patients presenting with chronic headache and frontal swelling.

Pott Puffy Tumor in Newly Diagnosed Human Immunodeficiency Virus

Background
Malaria in the United States is a rare disease with a reported number of cases typically 2,000 each year. In 2022, the State of Ohio had 32 malaria cases: 10 females and 22 males. This mosquito born illness poses a major threat to American travelers, military personnel, and US citizens living abroad in endemic areas. In returning travelers from high-risk countries, Malaria is the most common cause of febrile illness. Plasmodium ovale can remain dormant in the liver and presentation will be delayed. Chronic infection and relapsing disease will persist if the infection is not treated in the initial stages. Relapse episodes may occur months or years later. 

Case Presentation
We present a case of a 39-year-old male with a past medical history of chronic pancreatitis, depression, type 2 diabetes mellitus, gastroesophageal reflux disease, recent Epstein- Barr virus infection, who presents with fever, nausea, and vomiting beginning 10 days prior to admission. The patient has an extensive travel history abroad and returned from Angola six months ago. Prior to admission, he underwent treatment at a different hospital for sepsis, encephalopathy, fever, Epstein-Barr virus and babesia. His condition worsened and he left against medical advice and opted to seek treatment at our facility. With concern for malaria, immediate testing included: Giemsa-stained peripheral blood smear and malaria polymerase chain reaction. His anti-malarial treatment regimen included artemether-lumefantrine tablets for 3 days. Plasmodium species PCR was positive for Plasmodium ovale. The patient responded well to therapy, and continued follow-up at the infectious disease clinic. Likely, the progression and severity of his malaria infection progressively worsened due to delays in treatment and testing. Given his travel history, a concern for malaria should have been on the differential diagnosis at his previous hospital admission.

Discussion
Plasmodium ovale and Plasmodium vivax infection can remain dormant for months and will cause relapses despite anti-malarial prophylaxis treatment. An immunocompromised patient with infection can trigger nonspecific host defense mechanisms. The patient’s symptoms were initially attributed to Epstein-Barr virus infection; unfortunately, there was a missed malaria diagnosis. New research suggests climate change is increasing the mosquito population worldwide and likely causing higher malaria cases. Anti-malarial prophylaxis should be initiated and completed in patients traveling to endemic regions. Returning travelers with flu-like symptoms should be evaluated for malaria as soon as possible.


A Case of Plasmodium Ovale Malaria Presentation

Background
Cetuximab is a chimeric antibody used in treatment of metastatic colorectal cancer. Administered via an infusion, the most common side effect of cetuximab is mild allergic response. However, more serious reactions of anaphylaxis and cardiac arrest have been reported. Given the scarcity of the incidence of these reactions, and their reversible nature, there is limited understanding of predisposing factors and essentials of prevention. The present report aims to bridge this gap in knowledge and describes a case of cardiac arrest following cetuximab infusion. 

Case Presentation
A 68-year-old male with a medical history of stage 4 colorectal cancer with metastasis to the lung and liver presented to the emergency department (ED) with cardiac arrest following his first dose of cetuximab as a part of an outpatient clinical trial. Prior to infusion, the patient received 50 mg of Benadryl and underwent an electrocardiogram which revealed no abnormalities. Three minutes following initiation of cetuximab infusion, the patient developed pulseless electrical activity (PEA) and manual cardiopulmonary resuscitation (CPR) was begun. Vitals included a blood pressure of 95/38 mmHg and an oxygen saturation of 73%. En route to the emergency department (ED), the patient was intubated, and manual chest compressions were continued. Upon arrival, Acute Cardiac Life Support protocol was initiated and 2.3 mg of epinephrine was administered. The patient regained cardiac activity after fifteen minutes and was transferred to the critical care unit on an epinephrine drip. 

Initial laboratory testing revealed acidemia with a low bicarbonate level, hyponatremia and hyperchloremia, and normal potassium and magnesium levels. Elevated troponin T levels of (199 ng/L) were observed; however, echocardiography showed no abnormalities except for the slightly prolonged QTC interval in the ECG. Additionally, the patient had a high tryptase level of (63.6 ng/mL), suggesting an anaphylactic response. A CT chest image identified a new large left pneumothorax within a pre-existing subpleural bulla, bilateral rib fractures, and small pleural effusions likely due to recent CPR. The pneumothorax resolved with chest tube insertion. Although the patient initially improved, unfortunately he deteriorated with worsening hypoxia and aspiration pneumonia expired on the eighth day of admission.

Discussion
This case demonstrates the risk of life-threatening acute hypersensitivity responses following chemotherapy infusions, regardless of premedication with antihistamines. It underscores the importance of preliminary allergy testing, close monitoring of electrolytes and tryptase levels during transfusion, and quick access to crash carts.

Cardiac Arrest Following Cetuximab: A Fatal Iatrogenic Outcome

Background:
Coccidioidomycosis, commonly known as Valley Fever, and Paracoccidioidomycosis, referred to as the Mycosis of Lutz, Splendore, and Almeida, are the infections caused by two different types of dimorphic fungi, namely Coccidioides spp and Paracoccidioides spp, respectively, following inhalation of arthroconidia. While the San Joaquin Valley of California and the South-Central region of Arizona are the endemic regions for the Valley Fever, the most paracoccidioidomycosis cases are reported from Brazil, Colombia, Venezuela, and Argentina. The symptoms range from asymptomatic (60% of the total) coccidiomycosis cases to more severe forms, including disseminated infection. Chronic paracoccidioidomycosis comprises over 80 to 90% of total cases and patients with CNS involvement presents with clinical manifestations associated with space- occupying lesions. It is important to note that the disseminated coccidioidomycosis can result in meningitis, a condition if not treated, carries a significant mortality risk of 95% within a span of 2 years. Therefore, early detection plays a pivotal role in ensuring effective management. This article describes a case of disseminated coccidioidomycosis with neuroparacoccidioidomycosis co-infection in an otherwise healthy immunocompetent patient.

Case Presentation:
A 49-year-old Brazilian male presented with an episode of dizziness and near syncope. The head CT scan revealed two brain lesions at left temporal and parietal lobes with surrounding vasogenic edema causing mild mass effect. CT chest showed extensive bilateral small pulmonary nodules and small ill-defined opacities(figure-1), making it indistinguishable from infection due to other infectious, neoplastic, or inflammatory etiologies. Brain MRI revealed two ring-enhancing lesions with perilesional white matter edema. Subsequently, the CSF studies were positive for antibodies to coccidioides TP-antigen and F-antigen, confirming CNS involvement. The fungal isolate from bronchial washing was positive for growth of Paracoccidioides brasiliensis. The patient was treated with Dexamethasone, Fluconazole, and Levetiracetam. The patient is currently receiving the maintenance dose of fluconazole, which is for life.

Discussion:
Chronic paracoccidioidomycosis involving the lung can present as dry cough and dyspnea. The gold standard for diagnosing paracoccidioidomyosis is through isolation of Paracoccidioides spp. in culture and direct myocological examination. CNS involvement with paracoccidioidomycosis has been observed in 10-15 percent of patients presenting with seizures and focal neurologic signs, with positive ring-enhancing lesions with perilesional edema observed in MRI. Disseminated coccidioidomycosis is confirmed by antibody detection in CSF, warranting azole antifungal therapy. For patients with neuroparacoccidioidomycosis, TMP-SMX and amphotericin-B are effective. IV fluconazole is an alternative. Antifungal treatment should be provided to all disseminated coccidioidomycosis patients. To prevent relapse, lifelong antifungal therapy and follow-up are necessary. The role of a single azole for treatment of coexisting coccidioidomycosis and paracoccidioidomycosis infections is still unclear.

Conclusion:
Co-infection of disseminated coccidioidomycosis and paracoccidioidomycosis with neurologic involvement is a rare and unique presentation in a middle-aged otherwise immunocompetent individual. The role of a single azole for the treatment of coexisting coccidioidomycosis and paracoccidioidomycosis infections is still unclear. We aim to add more on literature on the treatment strategies for these disseminated fungal co-infections in the context of lifelong antifungal therapy needed to prevent relapse. Given that there are no proper guidelines for treating disseminated coccidioidomycosis and paracoccidioidomycosis co-infections for longer duration, further studies into the topic are recommended.

Disseminated Coccidioidomycosis with Neuroparacoccidioidomycosis Co-infection: A Rare Case Report and a Literature Review

Background
A post-dural puncture headache (PDPH) is a common complication following trauma from spinal or epidural procedures. While the gold standard of treatment is an epidural blood patch (EBP), numerous pharmaceuticals have been investigated to prevent and manage symptoms with varying results. In some studies, gabapentin has been shown to decrease the incidence and severity of PDPH and opioid consumption without significant adverse effects.
Case Presentation
A 22-year-old female presented with an intractable headache after a recent lumbar puncture (LP). She was receiving treatment with REPOCH and intrathecal (IT) methotrexate for Burkitt’s Lymphoma and had end-stage renal disease status-post a remote kidney transplant complicated by post-transplant lymphoproliferative disorder. At presentation, her associated symptoms included nausea, vomiting, and severe pain that improved with lying flat, consistent with a PDPH. Initial treatment included fluids, opioids, anti-emetics, and caffeine. However, the patient required hospitalization due to her symptoms for which Anesthesiology and Palliative
Medicine were consulted. Since the patient had future cycles of IT chemotherapy and was a high infectious risk due to her immunocompromised state, an EBP was not recommended. Steroids, acetaminophen, and NSAIDs were contraindicated given her neutropenic fever and renal dysfunction, respectively. Gabapentin 100mg TID was then recommended based on limited evidence. The patient experienced significant symptom relief with gabapentin, decreasing her opioid utilization from over 100 oral morphine equivalents to zero within 24 hours. Gabapentin was prescribed for the patient’s future LP schedule that included three days of prophylactic treatment followed by three days of therapeutic treatment. The patient’s last chemotherapy was completed a few months later without recurrence of her headache.
Discussion
Management of PDPH includes a wide variety of treatment options in the literature with new non-opioid medications undergoing ongoing investigation. Clinicians should consider the use of gabapentin in the treatment and prevention of PDPH for patients who fail standard therapies.

The Use of Gabapentin for Relief of Post-Dural Puncture Headache

Brugada syndrome is characterized by coved-type ST-segment elevations in the precordial leads associated with syncope, life-threatening ventricular tachyarrhythmias and sudden cardiac death. When typical ECG findings are present in the absence of symptoms, it is called Brugada pattern. About 25% of cases are associated with loss-of-function mutation of the cardiac sodium channel SCN5A while others may be triggered by drugs with sodium channel-blocking effects, electrolyte abnormalities, febrile states, or autonomic dysfunction.

A 33-year-old man presented with a 3-day history of intermittent substernal chest pressure. On hospital admission, ECG showed normal sinus rhythm without ST-segment changes and serial cardiac enzymes were normal. Given persistent symptoms and unremarkable recent exercise ECG-stress testing, cardiac CT-angiography was performed which revealed anomalous origin of the right coronary artery (RCA) with approximately 50% luminal narrowing. The patient underwent successful surgical reimplantation of the RCA. Cardiopulmonary bypass was weaned
off and the patient rewarmed from therapeutic hypothermia. Once normothermia was achieved, the patient developed ventricular fibrillation (VF). Following successful resuscitation, ECG revealed ST-segment elevations in V1 and V2 consistent with type 1 Brugada, which completely resolved spontaneously in the subsequent hours and was not reproducible with ajmaline challenge.

It is well known that hyperthermia may trigger Brugada syndrome in predisposed individuals. Studies have shown that mutated sodium channels result in temperature-dependent ionic changes. In febrile states, delayed sodium influx results in heterogeneous depolarization predisposing to VF. On the contrary, severe hypothermia (28.5C) causes sinus bradycardia, QT prolongation, widening of the QRS complex and the pathognomonic Osborn wave. Typical Brugada pattern has been rarely described in hypothermic states. Nonetheless, this pattern has been reproduced in animal models with cooling of the epicardium. Therapeutic hypothermia is targeted in the range of mild hypothermia (32-34C), where VF occurs only rarely, mainly in patients with primary arrhythmic disorders. Tan et al. described a case of transient typical Brugada ECG pattern upon rewarming from therapeutic hypothermia after sudden cardiac death of unknown etiology, with complete resolution with normothermia. These authors proposed that the Brugada pattern was hidden during the hypothermic state. In our patient, however, VF occurred only during the rewarming phase when normothermia was
achieved. We hypothesize that temperature increments, not necessarily hyperthermia, may be associated with increased risk of Brugada syndrome in susceptible patients. Although further research is needed, rewarming from therapeutic hypothermia requires careful monitoring for potentially lethal arrhythmogenic disorders.

A Warming Surprise: Brugada Syndrome After Rewarming from Therapeutic
Hypothermia

Background:
The spectrum of vascular access-site complications following cardiac catheterization can vary widely in severity ranging from simple to complex that can contribute to significant morbidity with a high economic burden and healthcare costs.

Aim:
The aim of the case presentation was to describe post-discharge delayed complication (acute limb ischemia) of cardiac catheterization due to noncalcified plaque.

Case Presentation:
A 58-year-old male with a history of coronary artery disease, diabetes mellitus, and hyperlipidemia underwent cardiac catheterization status-post angioplasty to the right coronary artery via right-femoral artery access. The patient was discharged home post-procedure, however, 8 hours later, he developed a sudden-onset cold foot, and worsening numbness, and tingling sensation in his right extremity that prompted him to present to the ER. Physical examination was notable for cold skin in his right leg with diminished dorsalis pedis and popliteal pulses, and a mild loss of “touch sensation” below the level of the knee. The patient was staged “IIa” on the Rutherford Acute Limb Ischemia score. Vitals and labs were within normal limits. CT Angiogram revealed focal high-grade stenosis in the right common femoral artery at the site of a recent arterial puncture from cardiac catheterization. This was likely secondary to nonocclusive, noncalcified plaque that has been disrupted from recent instrumentation. A Heparin drip was initiated and the patient underwent emergent revascularization with a diagnostic angiogram and balloon angioplasty of the right common femoral artery with the placement of a 27mm stent. A completion angiogram showed the resolution of the high-grade stenosis with good flow through the profound and superficial femoral artery. 

Discussion:
The risk of access-site complications following cardiac catheterization, although quite low, is increased with the femoral artery with an incidence estimated to be as high as 17%. Bleeding and hematoma are often reported, however, thrombosis is infrequent with mechanisms involving atherosclerotic plaque rupture or subintimal dissection of the plaque with secondary thrombosis. When the severity of limb ischemia is threatening, immediate anticoagulation followed by surgical revascularization is the most appropriate intervention. Thrombosis at the access site of cardiac catheterization can cause critical limb ischemia, particularly with the femoral artery, thus highlighting the need for careful post-operative follow-up. 


Acute limb ischemia due to iatrogenic plaque rupture in the common femoral artery at the site of cardiac catheterization - A Case Report

An anterior mediastinal teratoma in a child has never previously been reported presenting as a persistent dry cough. In this case, 5-year-old female with an initial history of respiratory syncytial viral infection, presented with a persistent cough for over 2 months. Asthma seemed the likely diagnosis initially. However, chest x-ray showed significant cardiomegaly. Echocardiogram was normal. CT scan of chest showed a large anterior mediastinal mass, likely teratoma. The mass was surgically resected, and diagnosis was confirmed by histopathology. In the future, it is critical physicians perform radiographical imaging to further investigate a persistent cough in pediatric patients.

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Saccharomyces cerevisiae (Baker’s Yeast) Pneumonia in an Immunocompromised Host

Next from 2023 AMA Research Challenge

Diarrheal Dilemma: G6PD-Deficiency Complicating Treatment of Antibiotic- Resistant Shigella in the MSM Population