Research Spotlight

Baylor Health Sciences Library brings to you each month the latest published research from the Baylor Scott & White and Texas A&M College of Dentistry communities. Each newly published article features the researcher, the abstract, and link to the full text. For information on including your own research, please contact Sudha Ramakrishnan at Sudha.Ramakrishnan@BSWHealth.org for BSWH or at sudharamakrishnan@tamu.edu for COD.


Posted June 17th 2021

Forkhead box F1 induces columnar phenotype and epithelial-to-mesenchymal transition in esophageal squamous cells to initiate Barrett’s like metaplasia.

Qiuyang D. Zhang Ph.D.

Qiuyang D. Zhang Ph.D.

De, A., Zhou, J., Liu, P., Huang, M., Gunewardena, S., Mathur, S.C., Christenson, L.K., Sharma, M., Zhang, Q. and Bansal, A. (2021). “Forkhead box F1 induces columnar phenotype and epithelial-to-mesenchymal transition in esophageal squamous cells to initiate Barrett’s like metaplasia.” Lab Invest 101(6): 745-759.

Full text of this article.

Multiple genome-wide association studies (GWAS) have linked Forkhead Box F1 (FOXF1) to Barrett’s esophagus (BE). Understanding whether FOXF1 is involved in initiation of Barrett’s metaplasia could allow FOXF1 to be used for risk stratification and for therapy. Two-dimensional cell cultures and three-dimensional organoid cultures and well-annotated human biopsies were used to determine the role of FOXF1 in BE pathogenesis. Multiple established esophageal squamous and BE cell lines were tested in gain- and loss-of-function studies. Initiation of a BE-like metaplastic change was evaluated by measuring characteristic cytokeratins and global gene expression profiling and by culturing organoids. Epithelial-mesenchymal transition (EMT) was evaluated by immunostaining for E-cadherin, vimentin and Snail, and by cell motility assay. Columnar esophageal epithelium of BE patients exhibited higher expression of FOXF1 compared to normal squamous esophageal epithelium of GERD patients (P < 0.001). Acidic bile salts induced nuclear FOXF1 in esophageal squamous cells. FOXF1 overexpression in normal esophageal squamous cells: (a) increased columnar cytokeratins and decreased squamous cytokeratins, (b) converted squamous organoids to glandular organoids, and (c) switched global gene profiles to resemble that of human BE epithelium (P = 2.1685e - 06 for upregulated genes and P = 8.3378e - 09 for downregulated genes). FOXF1 inhibition in BE cell lines led to loss of BE differentiation markers, CK7, and mucin 2. Also, FOXF1 induced EMT and promoted cell motility in normal esophageal squamous epithelial cells. FOXF1-induced genes mapped to pathways such as Cancer, Cellular Assembly and Organization, DNA Replication, Recombination, and Repair. In conclusion, FOXF1 promotes a BE-like columnar phenotype and cell motility in esophageal squamous epithelial cells, which may have a critical role in BE development. FOXF1 should be studied further as a biomarker for BE and as a target for BE treatment.


Posted June 17th 2021

Uterus transplantation and pregnancy induction: Approved protocol at the Royal Prince Alfred Hospital.

Giuliano Testa, M.D.

Giuliano Testa, M.D.

Georgevsky, D., Li, Y., Pather, S., Tejada-Berges, T., Robinson, D., Laurence, J., Campbell, N., Wyburn, K., Liyanagama, K., Narayan, R., Lutz, T., Chan, A., Heaney, S.A., Kitzing, Y.X., Anderson, L., Testa, G., Johannesson, L. and Marren, A. (2021). “Uterus transplantation and pregnancy induction: Approved protocol at the Royal Prince Alfred Hospital.” Aust N Z J Obstet Gynaecol may 6. [Epub ahead of print].

Full text of this article.

Absolute uterine factor infertility (AUFI) is defined as the absence of a uterus or the presence of a non-functional uterus. Before the first live birth from a uterus transplant in 2014, the only fertility options for women with AUFI were surrogacy and adoption. In November 2019, our team was granted approval for the first uterus transplant trial in Australia using known living donors. Our program is based on that of our overseas collaborators in Dallas, Texas; this team will also be proctoring us for our first two cases.


Posted June 17th 2021

2-Year Outcomes for Transcatheter Repair in Patients With Mitral Regurgitation From the CLASP Study.

Molly Szerlip M.D.

Molly Szerlip M.D.

Szerlip, M., Spargias, K.S., Makkar, R., Kar, S., Kipperman, R.M., O’Neill, W.W., Ng, M.K.C., Smith, R.L., Fam, N.P., Rinaldi, M.J., Raffel, O.C., Walters, D.L., Levisay, J., Montorfano, M., Latib, A., Carroll, J.D., Nickenig, G., Windecker, S., Marcoff, L., Cohen, G.N., Schäfer, U., Webb, J.G. and Lim, D.S. (2021). “2-Year Outcomes for Transcatheter Repair in Patients With Mitral Regurgitation From the CLASP Study.” JACC Cardiovasc Interv May 7;S1936-8798(21)00675-0. [Epub ahead of print].

Full text of this article.

OBJECTIVES: The study reports 2-year outcomes from the multicenter, prospective, single-arm CLASP study with functional mitral regurgitation (FMR) and degenerative MR (DMR) analysis. BACKGROUND: Transcatheter repair is a favorable option to treat MR. Long-term prognostic impact of the PASCAL transcatheter valve repair system in patients with clinically significant MR remains to be established. METHODS: Patients had clinically significant MR ≥3+ as evaluated by the echocardiographic core laboratory and were deemed candidates for transcatheter repair by the heart team. Assessments were performed by clinical events committee to 1 year (site-reported thereafter) and core laboratory to 2 years. RESULTS: A total of 124 patients (69% FMR, 31% DMR) were enrolled with a mean age of 75 years, 56% were male, 60% were New York Heart Association functional class III to IVa, and 100% had MR ≥3+. At 2 years, Kaplan-Meier estimates showed 80% survival (72% FMR, 94% DMR) and 84% freedom from heart failure (HF) hospitalization (78% FMR, 97% DMR), with 85% reduction in annualized HF hospitalization rate (81% FMR, 98% DMR). MR ≤1+ was achieved in 78% of patients (84% FMR, 71% DMR) and MR ≤2+ was achieved in 97% (95% FMR, 100% DMR) (all p < 0.001). Left ventricular end-diastolic volume decreased by 33 ml (p < 0.001); 93% of patients were in New York Heart Association functional class I to II (p < 0.001). CONCLUSIONS: The PASCAL repair system demonstrated sustained favorable outcomes at 2 years in FMR and DMR patients. Results showed high survival and freedom from HF rehospitalization rates with a significantly reduced annualized HF hospitalization rate. Durable MR reduction was achieved with evidence of left ventricular reverse remodeling and significant improvement in functional status. The CLASP IID/IIF randomized pivotal trial is ongoing.


Posted June 17th 2021

Inpatient management and post-discharge outcomes of hyperkalemia.

RESEARCHER'S NAME AS LISTED IN THE ALT TEXT BOX GOES HERE

Harold M. Szerlip M.D.

Davis, J., Israni, R., Mu, F., Cook, E.E., Szerlip, H., Uwaifo, G., Fonseca, V. and Betts, K.A. (2021). “Inpatient management and post-discharge outcomes of hyperkalemia.” Hosp Pract (1995) May 26;1-7. [Epub ahead of print]. 1-7.

Full text of this article.

OBJECTIVES: Patients with hyperkalemia are commonly treated in the inpatient setting; however, real-world evidence is limited. The purpose of this study was to describe the inpatient management and post-discharge outcomes among patients with hyperkalemia. METHODS: Electronic medical record data (2012-2018) were used to analyze US adult patients with an inpatient stay with hyperkalemia (≥1 potassium value >5.0mEq/L). Patient characteristics, treatments, and monitoring six months prior to and during the inpatient stay, and hyperkalemia recurrence and inpatient readmissions post-discharge were summarized and compared among patients with mild (>5.0-5.5mEq/L), moderate (>5.5-6.0), and severe (>6.0) hyperkalemia. RESULTS: Of the 21,793 patients, 69.2% had mild, 19.0% had moderate, and 11.8% had severe hyperkalemia during inpatient care. The most common inpatient treatments were temporizing agents (mild: 28.9%; moderate: 46.0%; severe: 73.0%), diuretics (32.7%; 37.1%; 34.6%), and sodium-polystyrene sulfonate (11.7%; 27.8%; 45.3%). Almost no patients (0.1%) received a potassium binder at discharge. Most patients (86.8%) had their potassium levels return to ≤5.0mEq/L during the inpatient stay. Death during the inpatient stay occurred in 12.3% of mild, 15.5% of moderate, and 19.5% of severe hyperkalemic patients. Within 30 days of discharge, hyperkalemia recurred in 13.3%, 15.4%, and 18.4% of patients with mild, moderate, and severe hyperkalemia, respectively. Additionally, 19.7%, 21.5%, and 19.6% of patients were readmitted to inpatient care within 30 days post-discharge. CONCLUSION: Among patients with hyperkalemia in the inpatient setting, treatment and normalization of serum potassium levels were common. However, death, readmission, and hyperkalemia recurrence were also fairly common across all cohorts. Future studies examining measures to reduce inpatient death, readmission, and hyperkalemia recurrence among patients with hyperkalemia in inpatient care are warranted.


Posted June 17th 2021

Safety and efficacy of Everolimus-Eluting bioabsorbable Polymer-Coated stent in patients with long coronary lesions: The EVOLVE 48 study.

Robert C. Stoler M.D.

Robert C. Stoler M.D.

Karmpaliotis, D., Stoler, R., Walsh, S., El-Jack, S., Potluri, S., Moses, J., Oldroyd, K., Banning, A., Webster, M., Zaman, A., Wu, W., Ahmed, M., Underwood, P. and Allocco, D. (2021). “Safety and efficacy of Everolimus-Eluting bioabsorbable Polymer-Coated stent in patients with long coronary lesions: The EVOLVE 48 study.” Catheter Cardiovasc Interv May 29. [Epub ahead of print].

Full text of this article.

OBJECTIVES: The EVOLVE 48 study evaluated the safety and effectiveness of the SYNERGY 48 mm stent for the treatment of long lesions. BACKGROUND: Clinical evidence supporting the use of very long stents during percutaneous coronary intervention (PCI) is limited. The bioabsorbable polymer SYNERGY stent has shown good long-term data in a broad population of patients undergoing PCI. METHODS: Patients with lesion length >34- ≤44 mm and reference vessel diameter (RVD) ≥2.5- ≤ 4.0 mm were enrolled in this prospective, multicenter, single-arm study. The primary endpoint was 12-month target lesion failure (TLF; composite of target lesion revascularization [TLR], target-vessel myocardial infarction [TV-MI], or cardiac death) compared to a prespecified performance goal (PG). RESULTS: A total of 100 patients with mean lesion length of 35.34 ± 7.15 mm (26 patients with lesion length > 40 mm) and mean RVD 2.72 ± 0.44 mm were enrolled. Moderate to severe calcification was present in 30% of the patients and 89% had pre-TIMI flow grade 3. The rates of technical and clinical procedural success were 100%. One-year TLF was observed in 4.1% patients compared to a prespecified PG of 19.5% (95% upper confidence bound = 9.1%; p < 0.0001). Cardiac death and TLR were each observed in one patient, and TV-MI in two patients treated with SYNERGY 48 mm stent. Between the 1-2-year timeframe, TV-MI occurred in one additional patient. None of the patients experienced a definite or probable stent thrombosis through 2 years. CONCLUSIONS: PCI of long coronary lesions with the 48 mm SYNERGY stent demonstrated good procedural and clinical outcomes through 2 years, supporting its clinical safety and efficacy.