Primecuts – This Week In The Journals

April 13, 2015


By Arvind Devanabanda, MD

Peer Reviewed

Last week, the president stated:“No challenge poses more of a public threat than climate change” at a round table discussion at Howard University. We are now four years into California’s drought and Governor Jerry Brown announced mandatory water restrictions ordering urban water use to be decreased by 25 percent. Many parts of Texas and Oklahoma also continue to experience severe droughts. The issue is again making global headlines, with the Pope to join the battle against climate change. Pope Francis, in his papal letter, will reach out to the United Nations Climate Change conference meeting to reduce global warming in Paris. For now, San Diego and much of California has started to look toward the sea as it plans to build additional desalination plants[1].

Does red cell storage duration affect cardiac surgery outcomes? [2]

Staying on the topic of essential needs, this week, the New England Journal of Medicine (NEJM) published a prospective, multi-centered trial focused red blood cell storage-time in transfusion for patients undergoing cardiac surgery. In this trial, 1100 adults were randomized to receive blood that was stored either for 10 days or less or 21 days or more. Participants in both groups received a median of 3 units of blood by postoperative day 7. Survival was assessed via the multiple organ dysfunction score (MODS), a measure sensitive to minor changes in clinical status that also incorporates mortality, ranging from 0 to 24, with higher scores indicating more severe disease. No significant difference in the increase in MODS was found between the short-term storage and longer-term storage groups (8.5 vs. 8.7, 95%CI -0.6 to 0.3, p=0.44). All-cause mortality between the two groups was also similar at day 7 (2.8% and 2.0%) and 28 days (4.4% and 5.3%). Further, the only adverse event with notable difference was hyperbilirubinemia, occurring more frequently in the longer-term storage group (1.5 mg per deciliter vs 0.8 mg per deciliter). Thus, the trial provides reassurance that dispensing older red blood cells is not significantly more harmful to patients.

Is manual thrombectomy beneficial during a percutaneous coronary intervention (PCI)? [3]

To date, several small trials concluded that thrombectomy during PCI, prior to stent deployment, decreases distal embolization and improves microvascular perfusion. In fact, practice guidelines were even changed to recommend routine manual thrombectomy if indicated, although new evidence questions if this is indeed beneficial. The Trial of Routine Aspiration Thrombectomy with PCI versus PCI alone in patients with STEMI (TOTAL) was published this week in NEJM to assess composite death from cardiovascular causes, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association class IV heart failure within 180 days of stent placement. The study randomized 10,732 patients with STEMI undergoing primary PCI to a strategy of upfront manual thrombectomy prior to PCI versus PCI alone. There was no significant difference in composite death (6.9% in thrombectomy group vs. 7% in PCI alone group, hazard ratio [HR], 0.99) or cardiovascular death between the two groups (3.1% with thrombectomy vs. 3.5% with PCI alone. HR 0.90). Despite lack of mortality difference, there was a notable increase in stroke within 30 days in the thrombectomy group (0.7% vs 0.3%. HR 2.06.) These findings caution against changing clinical practice prematurely and emphasize the importance of large multicenter trials to verify findings of smaller trials.

P53 induces cell cycle arrest, senescence and apoptosis and now also Ferroptosis. [4]

We already know that p53 is a binding transcription factor important in cell cycle mediated arrest, senescence and apoptosis. According to a study by Le Jiang, et al. now published in Nature, p53 also plays a significant role in ferroptosis, a non apoptotic and iron dependent form of oxidative cell death. New research shows that p53 inhibits cystine uptake and sensitizes cells to ferroptosis by repressing the expression of SLC7A11 a key component of the cystine/glutamate antiporter. This allows p53 to inhibit cystine uptake and sensitize the cell to death by ferroptosis, suggesting a novel p53 mediated mechanism of tumor suppression.

EMG guided biofeedback mechanisms in treating functional abdominal distention. [5]

Functional bloating, irritable bowel syndrome and functional dyspepsia are often associated with sensation and visibility of abdominal bloating via a mechanism that remains poorly understood. A prospective study by Barba et al., published in Gastroenterolgy, seeks to clarify the muscular activity behind the morphological changes involved in abdominal distention. Forty-two patients with functional intestinal disorders (Irritable Bowel Syndrome or Functional Bloating) were assessed with CT and EMG of the abdominothoracic wall during basal states compared to episodes of severe abdominal distention. Episodes of abdominal distention were associated with diaphragmatic and intercostal contraction, increase in lung volume and anterior abdominal wall protrusion. The EMG guided biofeedback treatment arm showed a reduction in the activity of the intercostal and diaphragm muscles by 19% and 18% respectively, and a reduced abdominal girth by 2.5 cm. For patients with functional gut disorders, this article suggests that abdominal distension is a behavioral response that can be reduced with EMG-guided, respiratory targeted biofeedback therapy that potentially improves patient symptoms.

Other interesting questions answered in this week’s literature

What is the impact of antithrombotic therapy on stroke and bleeding risk for otherwise low risk patients with atrial fibrillation? The American Journal of Academic Cardiology published a study showing that antithrombotic therapy for low-risk patients [defined as CHADS2-VASc score less than 0 for men and 2 for women] with the presence of 1 additional stroke risk factor increased the stroke rate at 1 year to 1.55 per 100 people. Bleeding risk also increased by 2.35-fold, and death increased by 3.12-fold, bringing into question the risk-benefit analysis of therapeutic anticoagulation in low-risk patients with atrial fibrillation. [6] http://content.onlinejacc.org/article.aspx?articleID=2196166

Would you consider atrial fibrillation ablation and mitral valve surgery at the same time? NEJM published a study from Icahn School of Medicine suggesting an increased rate of freedom from persistent atrial fibrillation during concurrent ablation and valvular surgery, but higher risk for implantation of a permanent pacemaker.7 Ultimately, this remains a personal decision in which several factors, including this new data, should be considered.[7]  http://www.nejm.org/doi/pdf/10.1056/NEJMoa1500528

And lastly, can dragons truly be dismissed as creatures of fantasy? If you too are wondering about this, be sure to check out this recent Nature article on how anthropogenic effects on the world’s climate may inadvertently pave the way for resurgence of these beasts. Or, if you are not in the mood for a good read, you can just enjoy dragons in the new season of Game of Thrones starting on HBO this week.[8] http://www.nature.com/nature/journal/v520/n7545/full/520042a.html

Dr. Arvind Devanabanda is a 1st year resident at NYU Langone Medical Center

Peer reviewed by Jessica Taff, MD, Chief Resident, Internal Medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References:

1. Gillis, J. “For Drinking Water in Drought, California Looks Warily to Sea” http://www.nytimes.com/2015/04/12/science/drinking-seawater-looks-ever-more-palatable-to-californians.html?hp&action=click&pgtype=Homepage&module=second-column-region&region=top-news&WT.nav=top-news.  Published April 11 , 2015

2. Steiner et al., “Effects of Red-Cell storage duration on Patients Undergoing Cardiac Surgery” New N Engl J Med 2015; 372:1419-1429 April 9, 2015 http://www.nejm.org/doi/full/10.1056/NEJMoa1414219

3. Jolly et al., “Randomized Trial of Primary PCI with or without routine manual thrombectomy” N Engl J Med 2015; 372:1389-1398 April 9, 2015 http://www.nejm.org/doi/full/10.1056/NEJMoa1415098

4. Le Jiang et al., “Ferroptosis as a p53-mediated activity during tumor suppression”. Nature 520,57–62, 02 April 2015  http://www.nature.com/nature/journal/v520/n7545/abs/nature14344.html

5. Barba et al., “Abdominothoracic mechanisms of functional abdominal distention and correction by biofeedback” Gastroenterology April 2015; Vol 148, issue 4, pages 732-739 http://www.sciencedirect.com/science/article/pii/S0016508514015315

6. Gregory Y.H. et al., “Oral anticoagulation , aspirin, or no therapy in patients with non valvular AF with 0 or 1 stroke risk factor based on the CHADS2-VASc score.” JACC . 2015; 65 (14): 1385- 1394. http://content.onlinejacc.org/article.aspx?articleID=2196166

7. Gillinov A et al., “ Surgical ablation of atrial fibrillation during Mitral valve surgery” N Engl J Med 2015; 372:1399-1409April 9, 2015 http://www.nejm.org/doi/pdf/10.1056/NEJMoa1500528

8. Hamilton A., et al., “ Zoology: Here be dragons” Nature 520 42-43 (02-April 2015) http://www.nature.com/nature/journal/v520/n7545/full/520042a.html