Research Spotlight

McCullough, P. A., G. David, T. M. Todoran, E. S. Brilakis, M. P. Ryan and C. Gunnarsson (2018). “Iso-osmolar contrast media and adverse renal and cardiac events after percutaneous cardiovascular intervention.” J Comp Eff Res 7(4): 331-341.

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AIM: To assess the relationship between type of contrast media (CM), iso-osmolar contrast media (IOCM) or low-osmolar contrast media (LOCM), and major adverse renal and cardiovascular events (MARCE). MATERIALS & METHODS: Coronary or peripheral angioplasty visits were stratified into CM cohorts: IOCM or LOCM. Multivariable regression analysis used hospital fixed effects to assess the relationship between MARCE events and type of CM. RESULTS: Among 333,533 visits (357 hospitals), the incidence of MARCE was 7.41%. After controlling for observable and unobservable time invariant within-hospital characteristics, administration of IOCM versus LOCM was associated with a 0.69% absolute and 9.32% relative risk reduction in MARCE rate. CONCLUSION: Our study indicates that as compared with LOCM, IOCM may be associated with reduction of MARCE events in coronary or peripheral angioplasty patients.

Manchio, J. V., S. M. Sentovich and W. R. Peters (2018). “What Every Colorectal Surgeon Should Know About: CMS Survey of Global Period Surgical Services.” Dis Colon Rectum 61(4): 419-420.

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What Surgeons Need to Do: Those surgeons in practices of 10 or more performing Medicare services in 1 of the 9 states included in the survey should submit the 99204 code for any care provided during the global period. This includes inpatient visits performed after the decision to perform the global procedure, postoperative inpatient care, visits to an extended care facility, outpatient visits for wound care, and any other office care provided in the global period. Failure to report these services may result in a 5% negative adjustment from CMS, although this penalty has not yet been implemented. Potential Issues and Implications of the Survey: There are a number of problems and implications related to this survey and the subsequent data analysis and potential revaluation of surgical services. Given the burdensome nature of the data reporting and survey participation, both required without additional surgeon compensation for the time and work involved, underreporting will certainly occur. How much underreporting will occur? Will the reporting accurately reflect the extent of postoperative care? Whereas these 293 procedures represent 87% of global services, how will the other 13% be adjusted, if at all? Another concern is that these procedure codes are used for all patients, not just Medicare fee-for-service patients. It is likely that other payers will apply the results of this CMS survey to all patients undergoing these procedures, with a corresponding decrease in reimbursement for all patients. If, however, the results are not generalized and applied to other patient populations, will the resulting relative decrease in reimbursement lead more practices to restrict the number of Medicare and Medicaid patients that they will care for? How will access to care be impacted by these changes? Conclusion: The Centers for Medicare and Medicaid Services has mandated that select surgeons in 9 states submit data that will be used to revalue the work provided by surgeons for 293 discrete Current Procedural Terminology codes, many of which are used by colorectal surgeons. Participants in the survey will not be compensated for the additional work required to collect and submit the requested data. Failure to accurately record all the work that is provided under the covered codes will likely result in undervaluation of the codes, decreased physician reimbursement for all surgeons, and, possibly, decreased access to care for Medicare and Medicaid patients. Therefore, all colorectal surgeons covered by this mandate are strongly encouraged to diligently report all services provided within the global period for the benefit of themselves and all of their surgical colleagues. (Excerpt from text, p. 410; no abstract available.)

Majtan, T., E. M. Bublil, I. Park, E. Arning, T. Bottiglieri, F. Glavin and J. P. Kraus (2018). “Pharmacokinetics and pharmacodynamics of PEGylated truncated human cystathionine beta-synthase for treatment of homocystinuria.” Life Sci 200: 15-25.

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AIMS: PEGylated human truncated cystathionine beta-synthase, lacking the C-terminal regulatory domain (PEG-CBS), is a promising preclinical candidate for enzyme replacement therapy in homocystinuria (HCU). It was designed to function as a metabolic sink to decrease the severely elevated plasma and tissue homocysteine concentrations. In this communication, we evaluated pharmacokinetics (PK), pharmacodynamics (PD) and sub-chronic toxicity of PEG-CBS in homocystinuric mice, wild type rats and monkeys to estimate the minimum human efficacious dose for clinical trials. MAIN METHODS: Animal models received single or multiple doses of PEG-CBS. Activity of PEG-CBS and sulfur amino acid metabolites were determined in plasma and used to determine PK and PD. KEY FINDINGS: The plasma half-lives of PEG-CBS after a single subcutaneous (SC) injection were approximately 20, 44 and 73h in mouse, rat and monkey, respectively. The SC administration of PEG-CBS resulted in a significant improvement or full correction of metabolic imbalance in both blood and tissues of homocystinuric mice. The PD of PEG-CBS in mouse was dose-dependent, but less than dose-proportional, with the maximal efficacy achieved at 8mg/kg. PEG-CBS was well-tolerated in mice and monkeys, but resulted in dose-dependent minimal-to-moderate inflammation at the injection sites and vacuolated macrophages in rats. Allometric scaling of animal data was linear and the estimated human efficacious dose was determined as 0.66mg/kg administered once a week. SIGNIFICANCE: These results provide critical preclinical data for the design of first-in-human PEG-CBS clinical trial.

Maisel, A. S., L. B. Daniels, I. S. Anand, P. A. McCullough and S. L. Chow (2018). “Utility of natriuretic peptides to assess and manage patients with heart failure receiving angiotensin receptor blocker/neprilysin inhibitor therapy.” Postgrad Med 130(3): 299-307.

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Levels of natriuretic peptides (NPs), such as B-type NP (BNP) and the N-terminal fragment of its prohormone (NT-proBNP), are well-established biomarkers for patients with heart failure (HF). Although these biomarkers have consistently demonstrated their value in the diagnosis and prognostication of HF, their ability to help clinicians in making treatment decisions remains debated. Moreover, some new HF drugs can affect concentrations of NPs, such as the prevention of BNP degradation by angiotensin receptor/neprilysin inhibitors (ARNIs), and may present a challenge in the interpretation of levels of BNP. Use of NT-proBNP measurement has been suggested in the context of ARNI therapy because its concentrations are not affected by neprilysin inhibition. As biomarkers are reconsidered in the context of ARNI therapy, cutoff levels and the effects of individual patient characteristics, such as renal function and age, on biomarker concentrations should be reassessed.