Case 331.

HISTORY: A 43-year-old male patient with no known past medical history presented to the emergency department with new-onset bitemporal headache, dizziness, and bilateral lower extremity weakness for 1 day. The patient denied chest pain, shortness of breath, cough, or recent exposure to sick individuals. He was not on any medications and denied alcohol or illicit drug use. Vital signs were unremarkable. Physical examination was notable for a left-sided pronator drift and bilateral dysmetria that was more pronounced on the left. Results of routine laboratory workup, including complete blood count, metabolic panel, and high-sensitivity troponin level, were normal. An electrocardiogram revealed sinus tachycardia with a heart rate of 102 beats per minute, T-wave inversions in the inferior leads, left axis deviation, incomplete right bundle branch block, and frequent premature ventricular contractions. A radiograph of the chest was unremarkable. CT of the head without contrast enhancement demonstrated no acute intracranial abnormities. MRI of the brain without contrast enhancement revealed multiple acute infarcts involving left posterior inferior cerebellar artery distribution, right cerebellar hemisphere, right mesial temporal lobe, and right posterior limb of the internal capsule. CT angiography of the head and neck showed an occlusion of the right posterior cerebral artery near its origin, with a trace of distal flow. Given that these findings were concerning for a cardioembolic etiology of acute ischemic stroke, transesophageal echocardiography was performed. This showed mild left ventricular systolic dysfunction with an ejection fraction of 40%, mild global hypokinesis, and an additional finding also seen at subsequent cardiac CT and MRI that will be disclosed in part 2 of the case. The patient was started on systemic anticoagulation and guideline-directed medical therapy for heart failure with reduced ejection fraction. CT of the chest showed no evidence of lymphadenopathy or abnormalities in the lung parenchyma or interstitium. Coronary CT angiography was performed (Fig 1), followed by cardiac MRI (Fig 2).

Pigment Epithelium-derived Factor (PEDF) Blocks Wnt3a Protein-induced Autophagy in Pancreatic Intraepithelial Neoplasms.

An increase in autophagy characterizes pancreatic carcinogenesis, but the signals that regulate this process are incompletely understood. Because canonical Wnt/ß-catenin signaling is necessary for the transition from early to advanced pancreatic intraepithelial neoplasia (PanIN) lesions, we assessed whether Wnt ligands and endogenous inhibitors of Wnt signaling modulate autophagy. In this study, canonical Wnt3a ligand induced autophagy markers and vacuoles in murine PanIN cells. Furthermore, pigment epithelium-derived factor (PEDF), a secreted glycoprotein known for its anti-tumor properties, blocked Wnt3a-directed induction of autophagy proteins. Autophagy inhibition was complemented by reciprocal regulation of the oxidative stress enzymes, superoxide dismutase 2 (SOD2) and catalase. Transcriptional control of Sod2 expression was mediated by PEDF-induced NFκB nuclear translocation. PEDF-dependent SOD2 expression in PanIN lesions was recapitulated in a murine model of PanIN formation where PEDF was deleted. In human PanIN lesions, co-expression of PEDF and SOD2 was observed in the majority of early PanIN lesions (47/50, 94%), whereas PEDF and SOD2 immunolocalization in high-grade human PanIN-2/3 was uncommon (7/50, 14%). These results indicate that PEDF regulates autophagy through coordinate Wnt signaling blockade and NFκB activation.

Acute Pericarditis Triggered by Severe Thyrotoxicosis.

Acute pericarditis is a common inflammatory disorder with several causes including infection, malignancy, acute myocardial infarction, and autoimmune disease. Acute pericarditis can rarely present in the setting of thyrotoxicosis. A 65-year-old man with a past medical history of HIV, diastolic dysfunction, and prediabetes presented with positional chest pain, respiratory distress, and altered mentation. He was found down on the ground in a lethargic state and was last seen normally five days before the presentation. On presentation, he was tachycardic and tachypneic, requiring supplemental oxygenation with a nonrebreather mask to maintain adequate oxygen saturation. Initial electrocardiogram (EKG) demonstrated diffuse ST-elevations with early repolarization, consistent with acute pericarditis. Laboratory diagnostics revealed elevated lactic acid, leukocytosis, acute kidney injury, undetectable thyroid stimulating hormone, and elevations in T3, T4, C-reactive protein, brain natriuretic peptide, and creatinine kinase. Given the patient's complex presentation involving thyrotoxicosis and pericarditis, a multidisciplinary team discussion was pursued involving critical care, cardiology, and endocrinology. He was started on intravenous methylprednisolone (subsequently transitioned to prednisone), methimazole, and metoprolol. Colchicine was subsequently added for the management of pericarditis and prednisone was continued (given concomitant thyroid disease) with a plan for tapering them off, per cardiology and endocrinology recommendations. A transthoracic echocardiogram revealed a small pericardial effusion. Anticoagulation was not initiated given the potential risk of developing a hemorrhagic pericardial effusion. Thyroid ultrasound was nonsuggestive of Graves' disease. Thyrotoxicosis may present with a constellation of symptoms, including acute pericarditis. Timely recognition with EKG and echocardiography can aid in prompt management.

Multiple recurrences of a left ventricular pseudoaneurysm: a case report.

Background: Takotsubo syndrome (TTS) is being diagnosed more often with its increased recognition over the past 2 decades and with the availability of imaging such as point-of-care echocardiography and tissue characterization by cardiovascular magnetic resonance (CMR). Case summary: A young man developed pericarditis and was treated with steroids. A few weeks later, he suffered classic TTS and then presented a week later with the rare complication of apical myocardial rupture and a left ventricular (LV) pseudoaneurysm. He subsequently sustained two recurrences, likely secondary to the poor tensile strength of the repair in the region of necrotic myocardium. Discussion: Various features of both syndromes are discussed herein (myopericarditis and TTS) as well as their classic imaging findings with an emphasis on the echocardiographic diagnosis of an LV pseudoaneurysm and differentiating it from an aneurysm. Furthermore, we elucidate the classic imaging findings of CMR in myocarditis, myocardial infarction with non-obstructive coronary arteries, and TTS. Lastly, we discuss treatment options for LV pseudoaneurysms and strategies to prevent recurrence.

Hydropneumopericardium Due to a Traumatic Esophageal-Pericardial Fistula.

Esophago-pericardial fistula is a rare, life-threatening condition, usually arising as a complication of benign esophageal disorders or iatrogenic causes. Prompt diagnosis via multimodality imaging is crucial, with computed tomography being the most sensitive. Management varies based on severity, with a growing trend toward early endoscopic interventions, which result in improved outcomes.

Environmental Pollution and Cardiovascular Disease: Part 2 of 2: Soil, Water, and Other Forms of Pollution.

With a growing body of evidence that now links environmental pollution to adverse cardiovascular disease (CVD) outcomes, pollution has emerged as an important risk factor for CVD. There is thus an urgent need to better understand the role of pollution in CVD, key pathophysiological mechanisms, and to raise awareness among health care providers, the scientific community, the general population, and regulatory authorities about the CV impact of pollution and strategies to reduce it. This article is part 2 of a 2-part state-of-the-art review on the topic of pollution and CVD-herein we discuss major environmental pollutants and their effects on CVD, highlighting pathophysiological mechanisms, and strategies to reduce CVD risk.

Environmental Pollution and Cardiovascular Disease: Part 1 of 2: Air Pollution.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Over the past 50 years, there has been a substantial decline in the incidence of CVD and related mortality in high-income countries, largely due to the mitigation of modifiable risk factors such as smoking, hypertension, and diabetes. However, a significant burden of CVD remains in low- to middle-income countries, despite their lower prevalence of traditional risk factors; other environmental factors, particularly pollution, play a significant role in this attributable risk. Mounting evidence underscores a strong association between pollution and adverse health effects, including CVD. This article is part 1 of a 2-part state-of-the-art review and discusses air pollution and its adverse effects on CVD, highlighting pathophysiological mechanisms and methods to reduce air pollution and exposure to these pollutants.

Pancoast Tumor With Cardiac Metastases and Intracardiac Thrombosis.

Pancoast tumor is a rare and aggressive form of lung cancer; cardiac metastasis is very uncommon. We present a case of advanced Pancoast tumor, with extensive cardiac metastases and intracardiac thrombosis in a woman presenting with dyspnea, shoulder pain, and weight loss. A contrast-enhanced chest computed tomographic scan revealed an apical mass, metastatic thoracic nodes, and filling defects within both ventricles. Further imaging with cardiac magnetic resonance imaging revealed 2 left ventricular masses infiltrating into the myocardium suggestive of metastatic disease, and a multilobulated mass within the right ventricle suggestive of intracardiac thrombus. She was initiated on anticoagulation for intracardiac thrombosis. Surgical pathology of biopsied tissue samples was consistent with advanced metastatic lung adenocarcinoma. She was a poor candidate for surgical intervention. Given the patient's goals of care, she was ultimately transitioned to comfort care.

COVID-19-Associated Coagulopathy: Ascending Aortic Thrombus.

The mechanism of arterial thrombosis in coronavirus disease 2019 (COVID-19) is not completely understood and is attributed to the complex interactions of endothelial injury, platelet hyperactivation, and activated pro-inflammatory cytokines. Management strategies may include a combination of surgery and anticoagulation, or anticoagulation alone. A 56-year-old woman with recent COVID-19 infection presented with chest pain and dyspnea. Chest CT angiography (CTA) and aortic magnetic resonance imaging revealed an intraluminal thrombus in the mid ascending aorta. A multidisciplinary team decided on heparin infusion. She was transitioned to apixaban and a three-month interval outpatient CTA revealed complete resolution of the aortic thrombus.

Glycogenic Hepatopathy: A Reversible Complication of Uncontrolled Diabetes Mellitus.

Glycogenic hepatopathy (GH) is a rare complication of long-standing uncontrolled type I diabetes mellitus (TIDM) resulting in liver dysfunction and hepatomegaly due to intrahepatic deposition of glycogen. Herein we present a 19-year-old male with a history of TIDM and multiple prior hospitalizations with diabetic ketoacidosis (DKA) who presented with nausea, vomiting, right upper quadrant pain, and massive hepatomegaly. Laboratory workup was consistent with DKA and revealed a greater than 10-fold increase in liver enzymes. Despite the resolution of DKA, his liver function was worsening, and further workup was indicated. Ultimately, he underwent a liver biopsy that showed swollen hepatocytes overloaded with intracytoplasmic glycogen consistent with glycogenic hepatopathy. It is an underestimated entity and physicians should have a high index of suspicion for GH in individuals presenting with liver dysfunction, hepatomegaly, and poor glycemic control in TIDM. Strict glycemic control may result in complete resolution of disease.

Pigment Epithelium-Derived Factor (PEDF) is a Determinant of Stem Cell Fate: Lessons from an Ultra-Rare Disease.

PEDF is a secreted glycoprotein that is widely expressed by multiple organs. Numerous functional contributions have been attributed to PEDF with antiangiogenic, antitumor, anti-inflammatory, and neurotrophic properties among the most prominent. The discovery that null mutations in the PEDF gene results in Osteogenesis Imperfecta Type VI, a rare autosomal recessive bone disease characterized by multiple fractures, highlights a critical developmental function for this protein. This ultra-rare orphan disease has provided biological insights into previous studies that noted PEDF's effects on various stem cell populations. In addition to bone development, PEDF modulates resident stem cell populations in the brain, muscle, and eye. Functional effects on human embryonic stem cells have also been demonstrated. An overview of recent advances in our understanding by which PEDF regulates stem cells and their potential clinical applications will be evaluated in this review.