Since the onset of the global pandemic in early 2020, coronavirus disease 2019 (COVID-19) has posed a multitude of challenges to health care systems worldwide. In order to combat these challenges and devise appropriate therapeutic strategies, it becomes of paramount importance to elucidate the pathophysiology of this illness. Coronavirus disease 2019, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is characterized by a dysregulated immune system and hypercoagulability. COVID-associated coagulopathy (CAC) was recognized based on profound d-dimer elevations and evidence of microthrombi and macrothrombi, both in venous and arterial systems. The underlying mechanisms associated with CAC have been suggested, but not clearly defined. The model of immunothrombosis illustrates the elaborate crosstalk between the innate immune system and coagulation. The rendering of a procoagulant state in COVID-19 involves the interplay of many innate immune pathways. The SARS-CoV2 virus can directly infect immune and endothelial cells, leading to endothelial injury and dysregulation of the immune system. Activated leukocytes potentiate a procoagulant state via release of intravascular tissue factor, platelet activation, NETosis, and inhibition of anticoagulant mechanisms. Additional pathways of specific relevance in CAC include cytokine release and complement activation. All these mechanisms have recently been reported in COVID-19. Immunothrombosis provides a comprehensive perspective of the several synergistic pathways pertinent to the pathogenesis of CAC.

COVID-19 disease is a viral illness that predominantly causes pneumonia and severe acute respiratory distress syndrome. The endothelial injury and hypercoagulability secondary to the inflammatory response predisposes severely ill patients to venous thromboembolism. The exact mechanism of hypercoagulability is still under investigation, but it is known to be associated with poor prognosis. The most common thrombotic complication reported among these patients is pulmonary embolism. To our knowledge, gonadal vein thrombosis is an uncommon phenomenon that has not been reported in the setting of COVID-19-associated coagulopathy. We report an unusual case of ovarian vein thrombosis and pulmonary embolism associated with COVID-19 presenting with abdominal pain. To our knowledge, this is the first reported case of COVID-19 with absent respiratory symptoms and presentation with venous thrombosis in an unusual location.

Thyroid cancer can be largely classified as well-differentiated, poorly differentiated, medullary and anaplastic. Differentiated thyroid cancer (DTC) includes follicular and papillary subtypes, with the incidence of papillary thyroid cancer (PTC) on the rise. The mainstay of treatment for DTC includes a combination of surgery, radioactive iodine (RAI) and levothyroxine suppression. DTC portends a favorable prognosis, even in the presence of distant metastases, with a 50% rate of 5-year survival largely due to tumor cell’s sensitivity to RAI therapy influencing disease outcome. In radioactive iodine refractory differentiated thyroid cancer (RAI-refractory DTC) there is a lower survival rate prompting the use of other therapeutic options available. RAI refractoriness is more common in older patients (age >40), large metastases and lesions that are fluorodeoxyglucose (FDG) avid on position emission tomography (PET). Over the past decade, Identification of genetic mutations in the signaling pathway involved in thyroid tumorigenesis has led to the approval of tyrosine kinase inhibitors (TKIs); Sorafenib and Lenvatinib in RAI-refractory DTC. Similarly, metastatic medullary thyroid cancer (MTC) implies an unfavorable 10-year survival rate of only 20% as the principal treatment options focuses on loco regional control via surgical and/or non-surgical options. The approval of TKIs such as Cabozantinib and Vandetanib has introduced an encouraging, novel, systemic therapeutic option for metastatic MTC. Lastly, anaplastic thyroid cancer (ATC) carries the worst prognosis with high recurrence rates. Treatment includes surgery, chemotherapy and external beam radiation. The FDA recently approved Dabrafenib plus trametinib for BRAF V600E mutated ATC. Considering the modality of chemotherapy and the expanding field of targeted therapies, the role of the oncologist and interaction with endocrinologist in the management of thyroid cancer needs further clarification aiming at collaborative management plans more than ever. This review summarizes the key phase III trials that led to the approval of TKIs in the treatment of DTC and metastatic MTC. Additionally, the review aims to clarify the patient selection criteria for initiation of TKIs and examine the implications, considerations and adverse effects prior to utilizing targeted therapy. Clinical trials are ongoing with promising results and may contribute to the addition of several targeted molecules and immune check point inhibitors to the therapeutic armamentarium for RAI-refractory DTC, medullary and anaplastic thyroid cancer.

With increasing legalization, marijuana has become the most commonly abused substance in the United States. Together with the introduction of more potent marijuana products over the years, more adverse events are being reported and clinically characterized. Delta-9-tetrahydrocannabinol (THC) is the active psychotropic component of marijuana, which acts mainly on G-protein cannabinoid receptors CB1 and CB2. Multiple isolated cases of arrhythmias associated with marijuana use have been published. In this manuscript we conduct a scoping study of a total of 27 cases of arrhythmia associated with marijuana. Most cases were reported in young males (81%) with a mean age of 28 ± 10.6 years. Atrial fibrillation (26%) and ventricular fibrillation (22%) were the most common arrhythmias reported. Brugada pattern was reported in 19% of the patients. Marijuana associated arrhythmia resulted in a high mortality rate of 11 %. While the exact mechanisms of arrhythmias associated with marijuana are not clear, several hypothesis have been introduced including the effect of marijuana on cardiac ion channels as well as its effects on the central nervous system. In this paper we discuss the possible mechanisms of marijuana induced arrhythmia citing the evidence available to-date.

Background. The COVID-19 infection which emerged in December 2019, is caused by the virus SARS-CoV-2. Infection with this virus can lead to severe respiratory illness, however, myocarditis has also been reported. The purpose of this study is to identify the clinical features of myocarditis in COVID-19 patients. Methods. A systematic review was conducted to investigate characteristics of myocarditis in patients infected with COVID-19 using the search term "Coronavirus" or "COVID" and "myocarditis," "heart," or "retrospective." Case reports and retrospective studies were gathered by searching Medline/Pubmed, Google Scholar, CINAHL, Cochrane CENTRAL, and Web of Science databases. 11 articles were selected for review. Results. COVID-19 myocarditis affected patients over the age of 50 and incidences among both genders were equally reported. Patients presented with dyspnea, cough, fever with hypotension and chest pain. Laboratory tests revealed leukocytosis with increased C-reactive protein, while arterial blood gas analysis demonstrated respiratory acidosis. All cardiac markers were elevated. Radiographic imaging of the chest showed bilateral ground glass opacities or bilateral infiltrates, while cardiac magnetic resonance imaging produced late gadolinium enhancements. Electrocardiography demonstrated ST-segment elevation or inverted T waves, while echocardiography revealed reduced left ventricular ejection fraction with cardiomegaly or increased wall thickness. Management with corticosteroids was favored in most cases, followed by antiviral medication. The majority of studies reported either recovery or no further clinical deterioration. Conclusion. Current available data on COVID-19 myocarditis is limited. Further research is needed to advance our understanding of COVID-19 myocarditis.

BackgroundNeuromyelitis optica (NMO) is a rare relapsing auto-immune disease of the central nervous system which is sometimes found in association with other autoimmune disorders including Sjogren’s syndrome. We present the case of a middle aged female with Sjogren’s syndrome (SS) and Neuromyelitis optica spectrum disorders (NMOSD) who had a rapidly declining neurological illness that responded to immunosuppressive therapy.Case presentationA 51-year-old female with Sjogren’s syndrome and recent history of varicella zoster infection presented with right upper and lower extremity weakness of one week duration. She was noted to have contrast enhancement at C2-C4 cord levels on cervico-thoracic MRI. Comprehensive work up was negative except for presence of a mild lymphocytic pleocytosis and oligoclonal bands in the CSF. She was diagnosed with transverse myelitis secondary to varicella zoster infection and was treated with high dose steroids in addition to acyclovir with improvement in her symptoms. Two months later she developed left upper and lower extremity weakness, bilateral dysesthesias and urinary incontinence. Repeat MRI of the cervico-thoracic spine revealed worsening enhancement at lower cervical cord levels (C5-7) with extension to T1. CSF analysis was unchanged; however immunological work up was abnormal for elevated NMO-IgG/AQP4 antibody. She was diagnosed with NMOSD and was treated with immunosuppressive therapy. Initially with IV methylprednisone and Cyclophosphamide therapy followed by Mycophenolate mofetil (MMF) maintenance therapy with good response. Repeat MRI 6 months later showed near complete resolution of previous abnormal cord signal changes.ConclusionOne needs to recognize the relationship between autoimmune diseases especially SS and NMOSD. The presence of NMO antibody has been associated with a relapsing disease course and a careful follow-up, besides use of remission maintenance agents such as MMF and Azathioprine are important to consider.

Ever since evidence about the increased risk of stent thrombosis with drug eluting stents (DES) surfaced in 2005, the Food and Drug Administration (FDA) has recommended the use of dual antiplatelet therapy (aspirin with P2Y12 inhibitor) following DES placement. The PLATO trial demonstrated lower mortality rates with the use of Ticagrelor when compared to clopidogrel (9.8% vs. 11.7%, p<0.001) when treating patients with acute coronary syndrome. Given their pleiotropic benefits, statins are today the second most prescribed drug in the United States and often co-prescribed with Ticagrelor. FDA's post market surveillance of Ticagrelor use along with statins in post-myocardial infarction care is now revealing novel and serious adverse events. We present two cases of rhabdomyolysis and acute renal failure (ARF) which develop while the patients were on statins and Ticagrelor. Case 1: A 66-year-old female presented with bilateral thigh pain for 3 days. One month prior to presentation, she was managed for non-ST segment elevation myocardial infarction (NSTEMI) and had been started on aspirin, ticagrelor and simvastatin. Laboratory values revealed creatinine kinase (CK) level at 40,000 U/L and creatinine 3.2 mg/dL suggesting rhabdomyolysis and ARF. Case 2: A 63-year-old male presented with generalized body aches and fatigue for 4 days. He had sustained STEMI two months before and received two drug eluting stents (DES) and aspirin, ticagrelor and rosuvastatin had been initiated. CK was 380,000 U/L and creatinine 7.94 mg/dL suggesting rhabdomyolysis and ARF. Both patients presented with rhabdomyolysis and acute renal failure within weeks after ticagrelor and statin were commenced. A review of the literature indicated that 11 similar cases of ticagrelor-induced ARF and rhabdomyolysis had been reported. Ticagrelor competes with statins when metabolized by cytochrome P450 (CYP) 3A4 leading to statin retention, leading to major adverse effects like rhabdomyolysis and acute renal failure. Our review is intended to alert clinicians about this important drug interaction.

The opioid prescription drug epidemic is not the only challenging drug abuse that the United States is facing. Over the past decade, the prevalence of another substance of abuse has dramatically; increased that is nitrous oxide, also known as ‘Whip-its’. As per the Substance Abuse and Mental Health Administration, there were twelve million users reported in 2012. Whip-its has become a popular trend among teenagers and young adults, as it is easily accessible. ‘Whip-Its!’ canisters containing nitrous oxide are available for purchase at grocery stores, on the internet, and various retailers without any age limit, warning or regulations. Reported cases of ‘Whip-its’ use have been linked to loss of consciousness, anoxic brain injury, cardiac arrest, and death. Yet, another result of chronic nitrous oxide abuse is that of spinal cord myelopathy due to vitamin B 12 deficiency. In this report we present a case of a 22-year-old male with daily abuse of inhaled nitrous oxide in the form of ‘Whip-its’, who presented with initial symptoms of presumed drug induced psychosis and gradually developed neurological focal deficits, and findings of sensorimotor peripheral neuropathy with myelopathy of the cervical spine and vitamin B12 deficiency.