Research Spotlight

Taylor, C.M., 2nd, Baer, H., Edgar, L., Jenkins, J.G., Harada, N., Helkowski, W.M., Zumsteg, J.M., Francisco, G.E., Sabharwal, S., Hamilton, R.G. and Mallow, M. (2020). “Improving the Assessment of Resident Competency: Physical Medicine and Rehabilitation Milestones 2.0.” Am J Phys Med Rehabil.

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In 2015, the Accreditation Council for Graduate Medical Education (ACGME) published the Physical Medicine and Rehabilitation (PM&R) Milestones 1.0 as part of the Next Accreditation System (NAS). This was the culmination of over 20 years of work on the part of the ACGME to improve graduate medical education competency assessments. The six core competencies were patient care (PC), medical knowledge (MK), systems-based practice (SBP), practice-based learning and improvement (PBLI), professionalism (PROF), and interpersonal and communication skills (ICS). While providing a good foundation for resident assessment, the PM&R Milestones 1.0 wasn’t without faults. With input from program directors, national organizations, and the public, the PM&R Milestones 2.0 strives to further advance resident assessment, providing improvements through the integration of the harmonized Milestones and the addition of a Supplemental Guide.

Anker, S.D., Butler, J., Filippatos, G., Khan, M.S., Ferreira, J.P., Bocchi, E., Böhm, M., Rocca, H.P.B., Choi, D.J., Chopra, V., Chuquiure, E., Giannetti, N., Gomez-Mesa, J.E., Janssens, S., Januzzi, J.L., Gonzalez-Juanatey, J.R., Merkely, B., Nicholls, S.J., Perrone, S.V., Piña, I.L., Ponikowski, P., Senni, M., Seronde, M.F., Sim, D., Spinar, J., Squire, I., Taddei, S., Tsutsui, H., Verma, S., Vinereanu, D., Zhang, J., Jamal, W., Schnaidt, S., Schnee, J.M., Brueckmann, M., Pocock, S.J., Zannad, F. and Packer, M. (2020). “Baseline Characteristics of Patients with Heart Failure with Preserved Ejection Fraction in the EMPEROR-Preserved Trial.” Eur J Heart Fail Nov 20. [Epub ahead of print.].

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BACKGROUND: EMPEROR-Preserved is an ongoing trial evaluating the effect of empagliflozin in patients with heart failure with preserved ejection fraction (HFpEF). This report describes the baseline characteristics of the EMPEROR-Preserved cohort and compares it with patients enrolled in prior HFpEF trials. METHODS: EMPEROR-Preserved is a phase III randomized, international, double-blind, parallel-group, placebo-controlled trial in which 5988 symptomatic HFpEF patients (left ventricular ejection fraction [LVEF] >40%) with and without type 2 diabetes mellitus (T2DM) have been enrolled. Patients were required to have elevated N-terminal pro B-type natriuretic peptide (NT-proBNP) concentrations (i.e. >300 pg/mL in patients without and >900 pg/mL in patients with atrial fibrillation) along with evidence of structural changes in the heart or documented history of HF hospitalization. RESULTS: Among patients enrolled from various regions (45% Europe, 11% Asia, 25% Latin America, 12% North America), the mean age was 72±9 years, 45% were women. Almost all patients had New York Heart Association (NYHA) Class II or III symptoms (99.6%), and 23% had prior HF hospitalization within 12 months. Thirty-three percent of the patients had baseline LVEF of 41-50%. The mean LVEF (54±9%) was slightly lower while the median NT-proBNP (974 [499-1731] pg/mL) was higher compared with previous HFpEF trials. Presence of comorbidities such as diabetes (49%) and chronic kidney disease (50%) were common. The majority of the patients were on angiotensin converting enzyme inhibitors/angiotensin receptor blockers/ARNi’s (80%) and beta-blockers (86%), and 37% of patients were on mineralocorticoid receptor antagonists. CONCLUSION: When compared with prior trials in HFpEF, the EMPEROR-Preserved cohort has a somewhat higher burden of co-morbidities, lower LVEF, higher median NT-proBNP and greater use of mineralocorticoid receptor antagonists at baseline. Results of the EMPEROR-Preserved trial will be available in 2021.

Anker, S.D., Butler, J., Filippatos, G., Khan, M.S., Marx, N., Lam, C.S.P., Schnaidt, S., Ofstad, A.P., Brueckmann, M., Jamal, W., Bocchi, E., Ponikowski, P., Perrone, S.V., Januzzi, J.L., Verma, S., Böhm, M., Ferreira, J.P., Pocock, S.J., Zannad, F. and Packer, M. (2020). “Effect of Empagliflozin on Cardiovascular and Renal Outcomes in Patients With Heart Failure by Baseline Diabetes Status – Results from the EMPEROR-Reduced Trial.” Circulation Nov 29. [Epub ahead of print.].

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Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve outcomes in patients with heart failure with reduced ejection fraction, but additional information is needed about whether glycemic status influences the magnitude of their benefits on heart failure and renal events. Methods: Patients with class II-IV heart failure and a left ventricular ejection fraction ≤40% were randomized to receive empagliflozin (10 mg daily) or placebo in addition to recommended therapy. We prespecified a comparison of the effect of empagliflozin in patients with and without diabetes. Results: Of the 3730 patients enrolled, 1856 (50%) had diabetes, 1268 (34%) had prediabetes (HbA1c 5.7-6.4%), and 606 (16%) had normoglycemia (HbA1c <5.7%). The risks of the primary outcome (cardiovascular death or hospitalization for heart failure), total hospitalizations for heart failure, and adverse renal outcomes were higher in patients with diabetes, but were similar between patients with prediabetes and normoglycemia. Empagliflozin reduced the risk of the primary outcome in patients with and without diabetes (hazard ratio 0.72 [95% CI 0.60-0.87] and 0.78 [95% CI 0.64-0.97], respectively, interaction P =0.57). Patients with and without diabetes also did not differ with respect to the effect of empagliflozin on total hospitalizations for heart failure, on the decline in estimated glomerular filtration rate over time, and on the risk of serious adverse renal outcomes. Among these endpoints, the effects of the drug did not differ in patients with prediabetes or normoglycemia. When analyzed as a continuous variable, baseline HbA1c did not significantly modify the benefits of empagliflozin on the primary outcome (P-interaction=0.40). Empagliflozin did not lower HbA1c in patients with prediabetes or normoglycemia and was not associated with increased risk of hypoglycemia. Conclusions: In the EMPEROR-Reduced trial, empagliflozin significantly improved cardiovascular and renal outcomes in patients with heart failure and a reduced ejection fraction, independent of baseline diabetes status and across the continuum of HbA1c.

Avila, M., Okai, A., Thakolwiboon, S., O’Bryan, C., Reddy Gopireddy, M.M. and Gorantla, S. (2020). “The effect of tonsillectomy on John Cunningham virus serological status in multiple sclerosis patients: A retrospective case-control study.” Mult Scler Nov 12;1352458520971822. [Epub ahead of print.].

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Tonsils are believed to be the initial site of the John Cunningham virus (JCV) infection. The long-term effect of childhood tonsillectomy on JCV status in multiple sclerosis (MS) patients has not been investigated. In this retrospective case-control study, we analyzed data of 144 JCV seropositive cases and 82 JCV seronegative controls from three outpatient MS clinics in the United States. Early tonsillectomy (before the age of 8) was reported among 8 (5.56%) JCV seropositive subjects and 19 (23.17%) controls. Early tonsillectomy was associated with JCV negative status (adjusted odds ratio = 5.39, 95% confidence interval = 2.13-13.62, p < 0.001) independent of age and gender.

Ustaoglu, A., Nguyen, A., Spechler, S., Sifrim, D., Souza, R. and Woodland, P. (2020). “Mucosal pathogenesis in gastro-esophageal reflux disease.” Neurogastroenterol Motil 32(12): e14022.

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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.