Research Spotlight

Webb, J.G., Hensey, M., Szerlip, M., Schäfer, U., Cohen, G.N., Kar, S., Makkar, R., Kipperman, R.M., Spargias, K., O’Neill, W.W., Ng, M.K.C., Fam, N.P., Rinaldi, M.J., Smith, R.L., Walters, D.L., Raffel, C.O., Levisay, J., Latib, A., Montorfano, M., Marcoff, L., Shrivastava, M., Boone, R., Gilmore, S., Feldman, T.E. and Lim, D.S. (2020). “1-Year Outcomes for Transcatheter Repair in Patients With Mitral Regurgitation From the CLASP Study.” JACC Cardiovasc Interv 13(20): 2344-2357.

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OBJECTIVES: The authors report the CLASP (Edwards PASCAL Transcatheter Mitral Valve Repair System Study) expanded experience, 1-year outcomes, and analysis by functional mitral regurgitation (FMR) and degenerative mitral regurgitation (DMR). BACKGROUND: The 30-day results from the CLASP study of the PASCAL transcatheter valve repair system for clinically significant mitral regurgitation (MR) have been previously reported. METHODS: Eligible patients had symptomatic MR ≥3+, were receiving optimal medical therapy, and were deemed candidates for transcatheter mitral repair by the local heart team. Primary endpoints included procedural success, clinical success, and major adverse event rate at 30 days. Follow-up was continued to 1 year. RESULTS: One hundred nine patients were treated (67% FMR, 33% DMR); the mean age was 75.5 years, and 57% were in New York Heart Association functional class III or IV. At 30 days, there was 1 cardiovascular death (0.9%), MR ≤1+ was achieved in 80% of patients (77% FMR, 86% DMR) and MR ≤2+ in 96% (96% FMR, 97% DMR), 88% of patients were in New York Heart Association functional class I or II, 6-min walk distance had improved by 28 m, and Kansas City Cardiomyopathy Questionnaire score had improved by 16 points (p < 0.001 for all). At 1 year, Kaplan-Meier survival was 92% (89% FMR 96% DMR) with 88% freedom from heart failure hospitalization (80% FMR, 100% DMR), MR was ≤1+ in 82% of patients (79% FMR, 86% DMR) and ≤2+ in 100% of patients, 88% of patients were in New York Heart Association functional class I or II, and Kansas City Cardiomyopathy Questionnaire score had improved by 14 points (p < 0.001 for all). CONCLUSIONS: The PASCAL transcatheter valve repair system demonstrated a low complication rate and high survival, with robust sustained MR reduction accompanied by significant improvements in functional status and quality of life at 1 year. (The CLASP Study Edwards PASCAL Transcatheter Mitral Valve Repair System Study [CLASP]; NCT03170349).

Swanson, G.P., Trevathan, S., Hammonds, K.A.P., Speights, V.O. and Hermans, M.R. (2020). “Gleason Score Evolution and the Effect on Prostate Cancer Outcomes.” Am J Clin Pathol Oct 20;aqaa130. [Epub ahead of print].

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OBJECTIVES: We evaluated how the changes in Gleason grading affected the long-term outcomes of a large prostatectomy cohort. METHODS: We obtained long-term follow-up (16.7 years) in 581 patients having undergone radical retropubic prostatectomy between 1985 and 1995. We excluded those with seminal vesicle and/or lymphatic involvement. We regraded the specimens according to contemporary guidelines and compared how this affected outcomes compared with their original (pre-1995) Gleason scoring. In total, 499 patients were evaluable. RESULTS: A Gleason score of 6 or less declined from 73% to 29%, and the number increased from 25% to 63% for a Gleason score of 7 and from 5% to 8% for a Gleason score of 8 to 9. As a result, for a Gleason score less than 7, biochemical failure decreased from 28% to 23%, metastatic disease 5% to 2%, and prostate cancer death from 5% to 3%. The same results were 50% to 37%, 11% to 7%, and 10% to 6% for a Gleason score of 7 and 86% to 71%, 43% to 32%, and 29% to 26% for a Gleason score more than 7, respectively. With the most recent grade grouping, for groups 1 to 5, biochemical failure occurred in 23%, 32%, 45%, 69%, and 78%, respectively. Metastatic disease occurred in 2%, 4%, 12%, 24%, and 56%, respectively. Prostate cancer-related death occurred in 2%, 4%, 9%, 21%, and 44%, respectively. CONCLUSIONS: The revised Gleason scores improved the outcomes in all risk groups. Based on Gleason score, patients with prostate cancer will appear to have better outcomes than they did before 2005, making any comparison tenable. The current grading system shows a consistent increased risk in biochemical failure, metastatic disease, and prostate cancer-related death with each successive grade.

Shearin, S.M., Medley, A., Trudelle-Jackson, E., Swank, C. and Querry, R. (2020). “Plantarflexor strength, gait speed, and step length change in individuals with Parkinson’s disease.” Int J Rehabil Res Oct 16. {Epub ahead of print].

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Parkinson’s disease affects the ability to walk often resulting in decreased independence and low quality of life. The purpose of this study was to examine differences in plantarflexor strength (PFS), gait speed, and step length in persons with Parkinson’s disease (PwP) and healthy peers using clinical measures. A secondary purpose was to examine the relationship between these gait components across disease severity. The study was a convenience sample of 71 PwP and 25 community healthy peers. Outcome measures included 10-Meter Walk, step length, and Calf-Raise Senior Test. PwP were separated into mild and moderate impairment groups using the Movement Disorders Society United Parkinson’s Disease Rating Scale Motor Subscale. Between group differences for gait speed (F2,93 = 24.560, P = 0.000), step length (F2,93 = 21.93, P = 0.000) and PFS (F2,93 = 19.49, P < 0.000) were observed. Post hoc testing determined a difference (P < 0.00) in gait speed, step length, and PFS testing between moderate impairment versus healthy peers and mild impairment. A difference (P = 0.045) in step length and a trend towards significance (P = 0.064) for PFS was found between healthy peers and mild impairment group. This study revealed that PwP with mild impairment also have significant changes in step length and trends toward plantarflexor weakness without a significant difference in gait speed. These early changes may warrant early assessment and intervention to prevent decline. This study may bring clinical focus onto the plantarflexor and step length for early comprehensive assessment and treatment of gait and mobility for PwP.

Ustaoglu, A., Nguyen, A., Spechler, S., Sifrim, D., Souza, R. and Woodland, P. (2020). “Mucosal pathogenesis in gastro-esophageal reflux disease.” Neurogastroenterol Motil Oct 28;e14022. [Epub ahead of print].

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BACKGROUND: Despite gastro-esophageal reflux disease affecting up to 20% of Western populations, relatively little is known about the molecular mechanisms underlying its most troublesome symptom: heartburn. Recent findings have unveiled the role of components of the esophageal mucosa in the pathogenesis of GERD including sensory nociceptive nerves and inflammatory mediators. Erosive esophagitis was long believed to develop as a result of acid injury at the esophageal lumen, but novel concepts suggest the generation of reflux-induced esophageal injury as a result of cytokine-mediated inflammation. Moreover, the localization and characterization of mucosal afferent nerves vary between GERD phenotypes and could explain the heterogeneity of symptom perception between patients who experience similar levels of acid reflux. PURPOSE: The purpose of this review is to consider the crosstalk of different factors of the esophageal mucosa in the pathogenesis of GERD, with a particular focus on mucosal innervation and molecular basis of acid-induced cytokine response. We discuss the current understanding of the mucosal response to acid injury, the nociceptive role of acid-sensitive receptors expressed in the esophageal mucosa, and the role of esophageal epithelial cells in initiating the onset of erosive esophagitis.

Souza, R.F. and Spechler, S.J. (2021). “Advances in Biomarkers for Risk Stratification in Barrett’s Esophagus.” Gastrointest Endosc Clin N Am 31(1): 105-115.

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Dysplasia currently is the primary biomarker used to risk stratify patients with Barrett’s esophagus, but dysplasia has a number of considerable limitations in this regard. Thus, investigators over the years have explored innumerable alternative molecular biomarkers for risk stratification in Barrett’s esophagus. This report focuses only on those biomarkers that appear most promising based on the availability of multiple published studies corroborating good results, and on the commercial availability of the test. These promising biomarkers include p53 immunostaining, TissueCypher, BarreGEN, and wide-area transepithelial sampling with computer-assisted 3-dimensional analysis