Research Spotlight

Posted January 15th 2021

Mast Cell Effects on Esophageal Smooth Muscle and their Potential Role in Eosinophilic Esophagitis and Achalasia.

Rhonda Souza M.D.

Rhonda Souza M.D.

Nelson, M.R., Zhang, X., Pan, Z., Spechler, S.J. and Souza, R.F. (2020). “Mast Cell Effects on Esophageal Smooth Muscle and their Potential Role in Eosinophilic Esophagitis and Achalasia.” Am J Physiol Gastrointest Liver Physiol Dec 23. [Epub ahead of print].

Full text of this article.

Mast cells and eosinophils are the key effector cells of allergic disorders. Although most studies on eosinophilic esophagitis (EoE), an allergic disorder of the esophagus, have focused on the role of eosinophils, recent studies suggest a major role for mast cells in causing the clinical manifestations of this disease. Cellular and animal studies have demonstrated that mast cells can cause esophageal muscle cells to proliferate and differentiate into a more contractile phenotype, and that mediators released by degranulating mast cells such as tryptase and histamine can activate smooth muscle contraction pathways. Thus, activated mast cells in the esophageal muscularis propria might cause esophageal motility abnormalities, including the failure of lower esophageal sphincter relaxation typical of achalasia. In addition, mast cells have been implicated in the pathogenesis of a number of neurodegenerative disorders of the central nervous system such as Alzheimer’s and Parkinson’s diseases, because degranulating mast cells release pro-inflammatory and cytotoxic mediators capable of damaging neurons. Such mast cell degranulation in the myenteric plexus of the esophagus could cause the loss of enteric neurons that characterizes achalasia. In this report, we review the molecular mechanisms of esophageal smooth muscle contraction, and how mast cells products might affect that muscle and cause neurodegeneration in the esophagus. Based on these data, we present our novel, conceptual model for an allergy-induced form of achalasia mediated by mast cell activation in the esophageal muscularis propria


Posted January 15th 2021

Positive Clinical Benefit on Patient Care, Quality of Life and Symptoms After Contact-Force Guided Radiofrequency Ablation in Persistent Atrial Fibrillation: Analyses from PRECEPT Prospective Multicenter Study.

Craig Delaughter M.D.

Craig Delaughter M.D.

Natale, A., Calkins, H., Osorio, J., Pollak, S.J., Melby, D., Marchlinski, F.E., Athill, C.A., Delaughter, C., Patel, A.M., Gentlesk, P.J., DeVille, B., Macle, L., Ellenbogen, K.A., Dukkipati, S.R., Reddy, V.Y. and Mansour, M. (2020). “Positive Clinical Benefit on Patient Care, Quality of Life and Symptoms After Contact-Force Guided Radiofrequency Ablation in Persistent Atrial Fibrillation: Analyses from PRECEPT Prospective Multicenter Study.” Circ Arrhythm Electrophysiol Dec 8. [Epub ahead of print].

Full text of this article.

Background – There is limited evidence on the long-term clinical benefits of catheter ablation in patients with persistent atrial fibrillation (PsAF). Methods – PRECEPT was a prospective, multicenter, single-arm Food and Drug Administration-regulated Investigational Device Exemption clinical study. Patients were followed up to 15 months after ablation. Outcomes included use of antiarrhythmic drugs (AADs), rate of cardioversions and cardiovascular hospitalization, Atrial Fibrillation Effect on Quality-of-Life (AFEQT) score, and Canadian Cardiovascular Society Severity of Atrial Fibrillation (CCS-SAF) score. Results – A total of 333 enrolled PsAF patients underwent ablation. The cardioversion rate decreased by 83% at the 9-15 months follow-up. AAD utilization decreased by 69% at 12-15 months post-ablation. The Kaplan-Meier estimate of freedom from cardiovascular hospitalization was 84.2% [95% confidence interval: 80.2%, 88.2%] at 15 months. Consistent improvements in mean AFEQT composite (+50.0) were seen at 6 months, sustained at 15 months, and exceeded the minimum clinically important difference. Improvements in AFEQT scores were significantly better among participants without documented atrial arrhythmia recurrences. By CCS-SAF symptom classification, over 80% of patients were asymptomatic (Class 0) at 15 months post-ablation compared to only 0.7% at baseline. Conclusions – Contact force-guided radiofrequency ablation of PsAF was associated with a significant decrease in AAD use, cardioversion rate and hospitalization. Clinically meaningful improvements in quality of life were observed in all patients. Majority of the patients (>80%) were asymptomatic at 15 months post-ablation. The positive clinical impact of improved quality of life and reduced healthcare utilization may help with shared decision making in PsAF treatment.


Posted January 15th 2021

Acute myocardial infarction secondary to mucormycosis after lung transplantation.

Chetan Naik M.D.

Chetan Naik M.D.

Naik, C.A., Mathai, S.K., Sandkovsky, U.S., Ausloos, K.A., Guileyardo, J.M., Schwartz, G., Mason, D.P., Gottlieb, R. and Grazia, T.J. (2021). “Acute myocardial infarction secondary to mucormycosis after lung transplantation.” IDCases 23: e01019.

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We present a case of a 57-year-old man who underwent bilateral lung transplantation for idiopathic pulmonary fibrosis. His immediately post-operative course was complicated by fever and cardiac arrest. Despite supportive care and broad-spectrum antibiotics, he experienced continued clinical decline. Autopsy results indicated angioinvasive mucormycosis and coronary arteritis resulting in acute myocardial infarction as the cause of death.


Posted January 15th 2021

Early multidrug regimens in new potentially fatal medical problems.

Peter McCullough, M.D

Peter McCullough, M.D

McCullough, P.A. and Oskoui, R. (2020). “Early multidrug regimens in new potentially fatal medical problems.” Rev Cardiovasc Med 21(4): 507-508.

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The SARS-CoV-2 (COVID-19) pandemic has been the greatest challenge to medical practice in decades. We have witnessed fear, panic, confusion, division, and a wide array of regulatory and public health responses to the crisis (National Institutes of Health, 2020). We believe it is important for all physicians to keep in mind this pandemic is an emergency crisis and is not a usual context for drug development, guidelines, and recommendations for patient practice. In cardiovascular medicine we have had many disruptive forces as the field has evolved and we have witnessed reasonable responses with respect to pharmacotherapy when there was an absence of randomized trials to first guide the approach. [No abstract; excerpt from article].


Posted January 15th 2021

Preclinical Pulmonary Fibrosis Circulating Protein Biomarkers.

Susan K. Mathai, M.D.

Susan K. Mathai, M.D.

Mathai, S.K., Cardwell, J., Metzger, F., Powers, J., Walts, A.D., Kropski, J.A., Eickelberg, O., Hauck, S.M., Yang, I.V. and Schwartz, D.A. (2020). “Preclinical Pulmonary Fibrosis Circulating Protein Biomarkers.” Am J Respir Crit Care Med 202(12): 1720-1724.

Full text of this article.

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive, irreversible scarring of the lung parenchyma that can require invasive diagnostic testing (1). Interstitial lung abnormalities (ILAs) have been described in the general population (2). Among asymptomatic first-degree relatives of patients with familial interstitial pneumonia (FIP), 14% have radiologic ILAs and 35% have interstitial abnormalities on biopsy (3). In the Framingham population, fibrotic ILAs were present in 1.8% of subjects ≥50 years of age (4) and associated with increased risk of death (5, 6), suggesting ILAs may be a harbinger of IPF. [No abstract; excerpt from article].