Research Spotlight

Alam, A., Milligan, G.P. and Joseph, S.M. (2020). “Reconsidering the Diagnostic Criteria of Right Ventricular Primary Graft Dysfunction.” J Card Fail Aug 7;S1071-9164(20)30901-5. [Epub ahead of print.].

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Primary graft dysfunction is defined as left and/or right ventricular (RV) failure occurring in the immediate post-transplant period in the absence of an immunologic or anatomic etiology. It is the leading cause of peri-operative mortality among patients receiving heart transplants1 making early and accurate diagnosis critical to optimizing outcomes. Diagnostic criteria were proposed by the International Society of Heart and Lung Transplantation,2 however the diagnosis of right ventricular primary graft dysfunction (RV-PGD) remains controversial. We review the currently accepted diagnostic criteria for RV-PGD, detail their inherent limitations, and propose a simplified approach to diagnosis and classification of RV-PGD severity. [No abstract available; excerpt from article.].

Upchurch, K., Wiest, M., Cardenas, J., Skinner, J., Nattami, D., Lanier, B., Millard, M., Joo, H., Turner, J. and Oh, S. (2020). “Whole blood transcriptional variations between responders and non-responders in asthma patients receiving omalizumab.” Clin Exp Allergy 50(9): 1017-1034.

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BACKGROUND: Anti-IgE (omalizumab) has been used for the treatment of moderate-to-severe asthma that is not controlled by inhaled steroids. Despite its success, it does not always provide patients with significant clinical benefits. OBJECTIVE: To investigate the transcriptional variations between omalizumab responders and non-responders and to study the mechanisms of action of omalizumab. METHODS: The whole blood transcriptomes of moderate-to-severe adult asthma patients (N = 45:34 responders and 11 non-responders) were analysed over the course of omalizumab treatment. Non-asthmatic healthy controls (N = 17) were used as controls. RESULTS: Transcriptome variations between responders and non-responders were identified using the genes significant (FDR < 0.05) in at least one comparison of each patient response status and time point compared with control subjects. Using gene ontology and network analysis, eight clusters of genes were identified. Longitudinal analyses of individual clusters revealed that responders could maintain changes induced with omalizumab treatment and become more similar to the control subjects, while non-responders tend to remain more similar to their pre-treatment baseline. Further analysis of an inflammatory gene cluster revealed that genes associated with neutrophil/eosinophil activities were up-regulated in non-responders and, more importantly, omalizumab did not significantly alter their expression levels. The application of modular analysis supported our findings and further revealed variations between responders and non-responders. CONCLUSION AND CLINICAL RELEVANCE: This study provides not only transcriptional variations between omalizumab responders and non-responders, but also molecular insights for controlling asthma by omalizumab.

Roberts, W.C. (2020). “Proceedings from the Editorial Board Meeting of The AJC in 2019.” Am J Cardiol 129: 120-121.

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Usually the editorial board of The American Journal of Cardiology (AJC) meets at the Annual Scientific Sessions of the American College of Cardiology which takes place usually in March of each year. The 2020 meeting was canceled because of the Covid-19 pandemic. Nevertheless, the following data summarize the journal’s performance in 2019. [No abstract available; excerpt from Editorial.].

Ward, M.A., Whitfield, E.P., Hasan, S.S., Ogola, G.O. and Leeds, S.G. (2020). “Objectively Confirmed Gastroesophageal Reflux Disease Following Per Oral Endoscopic Myotomy Higher in Obese Patients (BMI>30).” Surg Laparosc Endosc Percutan Tech Sep 2. [Epub ahead of print.].

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INTRODUCTION: Per oral endoscopic myotomy (POEM) is a promising minimally invasive therapy in the treatment of achalasia and other esophageal motility disorders. A concern surrounding POEM is the development of gastroesophageal reflux disease (GERD) postoperatively. This study was designed to report outcomes and identify risk factors for the development of postoperative GERD. METHODS: Patients who underwent POEM between January 1, 2015 and December 12, 2019 were prospectively followed in an Institutional Review Board approved database. All patients were invited for a full comprehensive workup 6 months post-POEM including symptom scores, pH testing, manometry and esophagogastroduodenoscopy. In a retrospective review of this database, those who developed postoperative GERD were compared with those who did not. RESULTS: There were 82 patients that met study criteria (median age 59). Indications for POEM include 35 type I achalasia, 16 type II achalasia, 21 type III achalasia and other spastic esophageal motility disorders, and 10 esophagogastric junction outflow obstruction. Mean Eckardt scores post-POEM were 2.67 compared with 6.79 pre-POEM (P<0.05). Mean integrated relaxation pressure improvement decreased from 27 to 13.1 (P<0.05). The presence of postoperative GERD was defined as an abnormal DeMeester score (>14.7) with pH testing off-medications or the presence of Grade C/D esophagitis on endoscopy. Thirty-five percent (29/82) of patients developed postoperative GERD following POEM. Negative predictive factors for the development of postoperative GERD include myotomy length and normal body mass index (BMI). Obesity (BMI>30) was a positive predictive risk factor in the development of GERD (P=0.029). CONCLUSIONS: POEM provides symptomatic relief and reduced Eckardt scores in patient with achalasia and other esophageal motility disorders. Patients who undergo POEM are at risk for developing gastroesophageal reflux disease especially in obese patients.

Ward, M.A., Ebrahim, A., Clothier, J.S., Prajapati, P.K., Ogola, G.O., Davis, D.G. and Leeds, S.G. (2020). “Factors that promote successful endoscopic management of laparoscopic sleeve gastrectomy leaks.” Surg Endosc Aug 11. [Epub ahead of print.].

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INTRODUCTION: Staple line leaks following laparoscopic sleeve gastrectomy (LSG) are associated with significant morbidity and mortality. Endoluminal techniques, including stent placement and endoluminal vacuum therapy (EVAC), have become viable options to treat these patients without the need for additional surgery. The purpose of this study was to define the conditions where certain endoscopic therapies are most likely to succeed compared to surgery. METHODS: An IRB approved prospectively maintained database was retrospectively reviewed for all patients treated for gastrointestinal leaks from July 2013 to March 2019. All patients who were treated for gastrointestinal leaks following LSG were included. Endpoints include success of leak closure and hospital-related morbidity for the patients treated solely by endoscopic only methods (EP) compared to the additional surgery group (SP). RESULTS: There were 39 patients (33 females; 6 males) with a median age of 45.9 years. The EP group included 23 patients (59%), whereas SP included 16 patients (31%). On average, the SP had longer days from sentinel surgery to our hospital admission (70 vs 41), a higher percentage of previous bariatric surgery prior to sentinel LSG (50% vs 17%), and a higher readmission rates following discharge (50% vs 39%). Total length of stay was also higher in the SP compared to the EP (45.4 vs 11). Using this data, a treatment algorithm was developed to optimally treat future patients who suffer from gastrointestinal leaks following LSG. CONCLUSIONS: Endoscopic therapies, such as EVAC, stent placement, internal drainage, and over-the-scope clips, have a higher chance of success if performed earlier to their sentinel surgery and if patients have had no prior bariatric surgeries. Patients who require additional surgery tend to have longer hospital stays and readmission rates. Using the treatment algorithm provided can help determine when endoscopic therapies are likely to succeed.