Sotirios Doukas’s research while affiliated with Saint Peter's University and other places

Apical ballooning syndrome (ABS), also known as Takotsubo cardiomyopathy, is a form of acute dilated cardiomyopathy associated with excessive catecholamine release. A 74-year-old female, chronic smoker with previously diagnosis of obstructive lung disease presented in the emergency department with severe shortness of breath and increase sputum production for the last 24hr. The patient was diagnosed with severe COPD exacerbation and received multiple doses of albuterol, methylprednisolone, ipratropium bromide/albuterol, and azithromycin. Despite this, the patient remained tachypneic and tachycardic with signs of impending respiratory failure. She was transferred to the ICU and intubated. After intubation, the patient received a continuous albuterol nebulizer, methylprednisolone, and ceftriaxone. A few hours later, the patient complained of chest pain, and EKG was done showing T wave inversion in lateral leads, troponin levels were 1.08 ng/mL (ULN 0.12ng/mL), and 2D Echo showed EF 50-55%, apical ballooning with dyskinesia, and inferior wall hypokinesis. Left heart catheterization showed non-obstructive coronary artery disease with 50% stenosis on the left anterior descending artery and distal ostial artery. Based on the previously recommended criteria, the diagnosis of the ABS was made. The patient had resolution of symptoms and echocardiogram findings after follow up. Although albuterol acts mainly on beta-2 receptors, cross-activation of beta-1 receptors can potentially lead to tachycardia. Previous case reports also support that excessive albuterol use in cases of asthma and COPD exacerbation may lead to ABS. This case may raise awareness that the extensive use of albuterol could have dramatic effects. Early switch to beta-2 agonist with higher specificity such as levalbuterol could be a reasonable approach in patients with severe COPD exacerbation.

Highlights Deregulation in MMR mechanism and miR-21, miR-155 and miR-451a are caused by chronic exposure to N-Nitrosamines, NNK and NDEA, and nicotine. Reduced hMSH2 and hMLH1 gene expression profiles and miRNA deregulations can be detected both at early stages of tobacco smoke-related carcinogenesis and in invasive cancers of the upper aerodigestive tract in smokers. MMR gene expression phenotypes are strongly linked to deregulated specific miRNAs, such as miR-21, miR-155, miR-34a and miR-451a. The activation of NF-κB may play a role in tobacco smoke-induced MMR dysfunction and carcinogenesis in the upper aerodigestive tract. Abstract Deregulation of the DNA mismatch repair (MMR) mechanism has been linked to poor prognosis of upper aerodigestive tract cancers. Our recent in vitro data have provided evidence of crosstalk between deregulated miRNAs and MMR genes, caused by tobacco smoke (TS) N-Nitrosamines, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in hypopharyngeal cells. Here, we explored whether chronic exposure to TS components can affect MMR mechanism and miRNA profiles in hypopharyngeal mucosa. Using a mouse model (C57Bl/6J wild type) of in vivo 14-week exposure to NNK (0.2 mmol/L) and N-Nitrosodiethylamine (NDEA; 0.004 mmol/L), with or without nicotine (0.02 μmol/L), we provide direct evidence that TS components can promote dysplasia, significant downregulation of Msh2 and Mlh1 genes and deregulation of miR-21, miR-155, miR-34a, and miR-451a. By analyzing eight human specimens from tobacco smokers and eight controls, we provide clinical evidence of a significant reduction in hMSH2 and hMLH1 mRNAs in hypopharyngeal squamous cell carcinoma (HSCC). In summary, deregulation of the MMR mechanism and miRNAs is caused by chronic exposure to TS-related N-Nitrosamines, with or without nicotine, in the early stages of upper aerodigestive tract carcinogenesis, and can also be detected in human HSCC. Thus, we encourage future studies to further elucidate a possible in vivo dose-dependent effect of individual or combined N-Nitrosamines, NNK and/or NDEA, and nicotine, on the MMR mechanism and their clinical testing to elaborate prognosis and risk assessment.

The coronavirus disease 2019 (COVID-19) includes an extensive spectrum of clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Previous studies have shown that SARS-CoV-2 often exhibits central nervous system (CNS) manifestations, including encephalitis, meningitis, and spinal cord pathologies. To date, few cases of COVID-19-associated transverse myelitis (TM) have been described. A 40-year-old unvaccinated man with no significant medical history presented to the emergency department complaining of fever, worsening burning sensation in his lower extremities, unsteady gait, and difficulty initiating urination for five days. Twelve days before presentation, the patient had tested positive for SARS-CoV-2 infection. Physical examination revealed hyperesthesia, starting around the nipple line (T4) and extending distally, involving the lower extremities, accompanied by symmetric weakness in the lower extremities. Magnetic resonance imaging of the thoracic spine with and without contrast revealed mild intramedullary signal abnormality at T3-T4 and T6-T8, confirming the suspicion of TM. Further laboratory testing revealed a C-reactive protein level of 67 mg/L, lactate dehydrogenase level of 181 mg/L, serum B12 level of 781 pg/mL, methylmalonic acid level of 165 nmol/L, folate of >24.5 ng/mL, and thyroid-stimulating hormone level of 0.481 μIU/L. Lumbar puncture was performed, and cerebrospinal fluid analysis revealed a cell count of 14 cells/µL, with 69% lymphocytes, glucose level of 81 mg/dL, protein level of 32 mg/dL, and negative cultures. Human immunodeficiency virus, antinuclear antibody screening, anti-DNA, rapid plasma reagin, Lyme serology, anti-SSA, and anti-SSB antibodies were unremarkable. Serum aquaporin-4 immunoglobulin G was negative, and myelin oligodendrocyte glycoprotein (MOG) antibodies were positive. The patient was treated with intravenous methylprednisolone and oral gabapentin and was discharged after five days when his urinary retention improved. Most previously reported cases of COVID-19-related TM were negative for autoimmune workup. Although the exact pathophysiology of COVID-19-related TM remains unclear, one hypothesis suggests that it is a consequence of the direct viral invasion. However, our patient had MOG antibodies, suggesting the possible involvement of a different mechanism. In MOG-associated TM, it has been suggested that MOG antibodies gain access to the CNS through disruption of the blood-brain barrier. This unique presentation demonstrates that further studies are needed to understand the effects of SARS-CoV-2 infection on the immune and nervous systems. It also highlights that young and otherwise healthy patients are at risk of severe COVID-19-related complications, including CNS disorders.