Primecuts – This Week In The Journals

April 25, 2016

tubman-20-us-money-billBy: Scott Statman, MD

 Peer Reviewed

The widely anticipated New York State presidential primaries were held this past Tuesday. In the Democratic contest Hilary Clinton won a 60% majority, solidifying her commanding lead over Bernie Sanders. On the Republican side Donald Trump also secured a decisive 60% majority. He maintains a significant lead over Ted Cruz, however significant doubt remains over Mr. Trump’s ability to secure enough delegates should he not win the 1,237 needed to avoid a contested convention in Cleveland this July [1].

In other news, the United States Treasury Department announced that Harriett Tubman will replace Andrew Jackson on the new $20 bill to be released in 2020 [2]. In response presidential candidate Donald Trump stated, “I think it’s pure political correctness…Andrew Jackson had a great history. I think it’s very rough when you take somebody off the bill [3].”

In medical news, the Centers for Disease Control (CDC) released a review acknowledging for the first time a causal relationship between Zika virus infection and birth defects such as microcephaly. This is intended to encourage increased focus on Zika virus prevention, diagnosis, and research [4].

Proton Pump Inhibitors Again Linked to Increased Risk of Chronic Kidney Disease

A large retrospective cohort study [5] used national Veteran’s Affairs databases to identify new users of proton-pump inhibitors (PPIs, n=173,321) and H2 blockers (H2Bs, n=20,270) with normal baseline estimated glomerular filtration rate (eGFR) and ≥ 1 additional measurement of renal function over a 5 year period after starting each medication. Results showed a statistically significant association between PPI use and risk of chronic kidney disease (CKD) compared to H2B use (36.8 vs 25.7/1000 person-years, HR 1.28, CI 1.23-1.34, attributable risk 1.11%, number needed to harm [NNTH] 90). Similarly, a significant association was found between PPI use and CKD progression, as evidenced by increased rates of eGFR decline >30% (61.7 vs 45.3 per 1000 person-years, HR 1.32, CI 1.28-1.37, attributable risk 1.63%, NNTH 61). PPIs also increased the risk progression to end-stage renal disease (4.13 vs 2.65 per 1000 person-years, HR 1.96, CI 1.21-3.18, attributable risk 0.01%, NNTH of 6780). Importantly, investigators found a graded association between duration of exposure and risk of renal outcomes. These results corroborate a recent cohort study [6] that showed an association between self-reported PPI use in 10,482 participants and risk of developing CKD. The pathophysiology behind these findings likely relates to the knowledge that PPIs increase the risk of acute intersitial nephritis (AIN), which is often subclinical, delaying diagnosis and allowing progression to chronic interstitial nephritis and CKD [7]. Despite the low incidence of outcomes reported in this study, it raises more concern over the frequent long-term use of PPIs, often without strong clinical indications.

Use of coronary CTA to guide management of angina due to suspected coronary artery disease

The 2015 SCOT-HEART Trial [8] showed that coronary computed tomography angiography (CCTA) is useful for clarifying the diagnosis of angina due to coronary artery disease (CAD) when added to the standard of care such as stress testing. In a follow up study [9] using the same data, investigators compared CCTA findings with those seen during invasive coronary angiography (ICA). The trial included 4,146 adult subjects referred to Scottish cardiology clinics with suspected angina due to CAD. They were randomized to receive either CCTA or standard care and followed for a median of 20 months. Between groups there was no difference in the number of ICA procedures however in the CCTA group results were less likely to show normal coronary arteries (20 vs 56, HR 0.39, p < 0.001) and more likely to show obstructive CAD (283 vs 230, HR 1.29, p=0.005). There was a non-significant trend towards more coronary revascularization procedures (233 vs 201, HR 1.20, p = 0.061). As a result of CCTA results, clinicians were more likely to discontinue (77 vs 8, OR 10.75, p < 0.001) or initiate (293 vs 84, OR 4.21, p < 0.001) preventative oral medications. Importantly, CCTA decreased rates of fatal and nonfatal myocardial infarction (26 vs 42, HR 0.62, p=0.053). This effect was more pronounced when only including events taking place ≥ 50 days after CCTA (17 vs 34, HR 0.50, p=0.020), coinciding with the timing of preventative therapy implementation. These results suggest that CCTA allows clinicians to more effectively select patients for ICA and choose more appropriate preventative medications. A major limitation of this study is the low event rate despite the large sample size, however the results suggest a potential future role for CCTA in the workup of suspected stable angina.

Controversial re-evaluation of the Minnesota Coronary Experiment suggests that decreasing dietary saturated fats may not lead to decreased mortality.

The diet-heart hypothesis suggests that replacing saturated fats with oils rich in linoleic acid (such as in corn, sunflower seeds, and soybeans) decreases mortality. Investigators called this into question with the recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE). This study [10], conducted from 1968-1973, included 9,570 adult subjects admitted to a nursing home and 6 state mental facilities in Minnesota. Subjects were randomized to receive either a control diet containing significant amounts of trans-fat or an experimental diet that used corn oil to decrease dietary saturated fat and increase linoleic acid. Investigators recovered serum cholesterol data from 2,355 of 2,403 participants enrolled in the study for ≥ 1 year. The experimental diet significantly lowered serum cholesterol (mean change -31.2 mg/dL or -13.8%, p < 0.001) compared to the control group (-5.0 mg/dL or -1.0%, p < 0.001). Surprisingly researchers found that a 30 mg/dL decrease in serum cholesterol was associated with increased risk of all-cause mortality in the experimental group (HR 1.22, CI 1.09-1.51), control group (HR 1.28, CI 1.09-1.51), and all groups combined (HR 1.22, CI 1.14-1.32). This appears to be driven by the subgroup age ≥ 65, in which for all groups combined the same decrease in cholesterol was associated with a 35% increased mortality (HR 1.35, CI 1.18-1.54). This may be explained by the fact that linoleic acid, an omega-6 fatty acid commonly found in processed foods, places great oxidative stress on the body. This post-hoc analysis of an incomplete data set has numerous limitations as pointed out by nutrition experts [11], however it highlights the need for further research into the diet-heart hypothesis.

Extended 10-year follow up of STICH trial shows that CABG is superior to medical therapy alone in ischemic cardiomyopathy  

In the 2011 Surgical Treatment for Ischemic Heart Failure (STICH) trial [12], investigators randomized 1,212 patients with an ejection fraction ≤ 35% and coronary artery disease (CAD) to receive either coronary artery bypass grafting (CABG) or medical therapy alone.  After a median of 4.7 years of follow up, results showed no significant difference between groups with respect to death from any cause. In the STICH-Extension Study (STICHES) [13] investigators followed the same subjects for a median of 9.4 years. Results showed that CABG significantly reduced the risk of death from any cause compared to medical therapy alone (58.9% vs 66.1%, HR 0.84, CI 0.73-0.97). The CABG group survived 1.44 years longer and the number needed to treat to prevent one death was 14. Similar results were found with respect to death from cardiovascular causes (40.5% vs 49.3%, HR 0.79, CI 0.66-0.93). It should be noted that 119 patients in the medical therapy group eventually underwent CABG, and 55 patients in the CABG group never underwent surgery. When analyzing the data as-treated (instead of intention-to-treat as above), results suggest that the crossovers led to an underestimation of the benefits of CABG. These results suggest that after accounting for the increased 30-day mortality following surgery (3.6% in this trial), CABG plus medical therapy provides significant benefit over medical therapy alone in patients with ischemic cardiomyopathy.


An international committee of thyroid experts changed the nomenclature for the encapsulated follicular variant of papillary thyroid carcinoma to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). They hope to prevent the aggressive treatment of this common indolent tumor, which represents 10-20% of all thyroid cancers [14].

A group of NYU researchers including Dr. Martin Blaser discovered that helminth infection protects susceptible mice from developing inflammatory bowel disease (IBD) by promoting changes in gut flora. This is further evidence that alterations in the microbiome contribute to the rising incidence of IBD in developed nations. [15].

An analysis of data from 3,387 US hospitals found that following passage of the Affordable Care Act (ACA) in 2010, readmission rates decreased while observation unit stays increased. After finding no significant association between these changes, investigators concluded that hospitals’ responses to financial incentives, not increased use of observation units, account for decreased readmissions following passage of the ACA [16].

Dr. Scott Statman is a 1st year internal medicine resident at NYU Langone Medical Center

Peer reviewed by Anish B. Parikh, MD, Chief Resident, Department of Medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons



  4. Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika Virus and Birth Defects – Reviewing the Evidence for Causality. N Engl J Med. Published Online: April 13, 2016. doi: 10.1056/NEJMsr1604338.
  5. Xie Y, Bowe B, Li T, Xian H, Balasubramanian S, Al-aly Z. Proton Pump Inhibitors and Risk of Incident CKD and Progression to ESRD. J Am Soc Nephrol. Published Online: April 14, 2016. doi:10.1681/ASN.2015121377.
  6. Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J, Grams ME: Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Intern Med 2016; 176: 238–246.
  7. Moledina DG, Perazella MA. Proton Pump Inhibitors and CKD. J Am Soc Nephrol. Published Online: April 14, 2016. doi:10.1681/ASN.2016020192.
  8. The SCOT-HEART Investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet 2015;385:2383–91.
  9. Williams MC, Hunter A, Shah AS, Assi V, Lewis S, Smith J, Berry C, Boon NA, Clark E, Flather M, Forbes J, McLean S, Roditi G, van Beek EJ, Timmis AD, Newby DE, SCOT-HEART investigators. Use of Coronary Computed Tomographic Angiography to Guide Management of Patients With Coronary Disease. J Am Coll Cardiol. 2016;67(15):1759-68.
  10. Ramsden CE, Zamora D, Majchrzak-Hong S, Faurot KR, Broste SK, Frantz RP, Davis JM, Ringel A, Suchindran CM, Hibbeln JR. Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73). BMJ. 2016;353:i1246.
  11. http://11.
  12. Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med. 2011;364:1607-1616.
  13. Velazquez EJ, Lee KL, Jones RH, et al. Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy. N Engl J Med. 2016;374(16):1511-1520.
  14. Nikiforov YE, Seethala RR, Tallini G, et al. Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA Oncol. Published online April 14, 2016. doi:10.1001/jamaoncol.2016.0386.
  15. Ramanan D, Bowcutt R, Lee SC, et al. Helminth infection promotes colonization resistance via type 2 immunity. Science. Published Online: April 14, 2016. doi: 10.1126/science.aaf3229.
  16. Zuckerman RB, Sheingold SH, Orav EJ, Ruhter J, Epstein AM. Readmissions, Observation, and the Hospital Readmissions Reduction Program. N Engl J Med. 2016;374(16):1543-1551.