Primecuts – This Week In The Journals

June 29, 2015

waterlooBy Olivia Begasse De Dhaem, MD

Peer Reviewed

According to the latest data from UNHCR, the United Nations Refugee Agency, war and persecution displaced a total of 59.4 million people in 2014, primarily in developing countries. [1] As the number of asylum-seekers fleeing from countries like Syria and Eritrea to Europe increases, the E.U. gave up on the plan for mandatory quotas to spread the refugees across the 28 E.U. countries, and suggested a voluntary program instead. [2] Although there was no mass deportation after the recent immigration law deadline in the Dominican Republic, 12,000 Haitian migrants and children of migrants without official Dominican birth certificates crossed into Haiti in the past week. [3] At home, the mourning process for the victims of the mass shooting in Charleston continues as does the ongoing debate over race relations in modern America. In contrast to this disheartening news, the Supreme Court brought us hope of equality and fraternity by recognizing same-sex marriage as a federal right and also ruled to allow federal health insurance subsidies to poor and middle-class Americans, thereby upholding one of the main tenets of the Affordable Care Act. [4,5,6] Let’s now look at the significant developments in the medical world from the past few weeks.

Decreasing the bone loss associated with antiretroviral therapy initiation. [7]

The Annals just published a multicenter, randomized, double-blind, placebo-controlled study evaluating the effect of vitamin D3 and calcium supplementation on the bone mineral density (BMD) loss associated with treatment of HIV with efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). Previous studies have shown an initial 2-6% decrease in hip BMD during the first 24-48 weeks of treatment with this regimen. In this study, 165 patients were enrolled, 86 taking a daily placebo and 79 taking daily oral doses of 4000 IU of vitamin D3 and 1000 mg of calcium carbonate during their EFV/FTC/TDF treatment. Both groups showed a significant decrease in total hip BMD after 48 weeks of treatment. The primary endpoint was the percent change in total hip BMD between baseline and after 48 weeks of treatment, and was found to be significantly lower in the supplementation group than in the placebo group (1.36% median decline, IQR 3.43%-0.50% vs. 3.22% median decline, IQR 5.56%- 0.88%, p = 0.004). The supplementation group had no change in PTH level and a smaller increase in markers of bone turnover compared to the placebo group. In conclusion, this study suggests that vitamin D3 and calcium supplementation lowers the BMD decline associated with initiation of this important anti-retroviral treatment regimen, but further studies are needed to assess the potential long term benefits in terms of preventing fractures. 

A promising therapeutic target for pulmonary arterial hypertension. [8]

Nature Medicine recently published a study evaluating the efficacy of selective enhancement of endothelial bone morphogenetic protein type II receptor (BMPR-II) with the BMP9 ligand to reverse pulmonary arterial hypertension (PAH). Evidence has shown that loss of the endothelial BMPR-II signaling leads to excess proliferation of endothelial cells, which narrows the precapillary pulmonary arteries and thus increases pulmonary vascular resistance. In cultures, the BMP9 ligand was shown to prevent pathological angioproliferation and enhance the monolayer integrity of the pulmonary arterial endothelial cells. The researchers in this study created a BMPR-II deficiency in an experimental mouse model which subsequently led to spontaneous development of PAH. Treating the experimental mice for four weeks with daily BMP9 reversed their PAH and returned their right ventricular systolic pressure to the level of wild type mice. Similar results were obtained with BMP9 treatment in rat models with different causes of PAH: a monocrotaline model with decreased BMPR-II expression, and a PAH model in which rats were exposed to chronic hypoxia and a VEGF receptor blocker. This study is a proof of concept that recombinant BMP9 ligand might reverse established PAH regardless of whether or not patients have BMPR2 mutations.

Antibiotic therapy as initial management of acute appendicitis instead of appendectomy? [9]

The APPAC trial published in JAMA this week is a multicenter, noninferiority, randomized clinical trial with intention-to-treat analysis. 273 of the 529 enrolled patients with uncomplicated acute appendicitis confirmed by CT scan were assigned to the early appendectomy group. The other patients were given IV ertapenem 1g daily for 3 days followed by oral levofloxacin 500mg daily with metronidazole 500mg TID for the next 7 days. The primary endpoints were successful completion of the appendectomy for the surgical group, and resolution of the appendicitis with neither appendectomy nor recurrence during the one-year follow-up for the antibiotics group. The surgical group had a 99.6% success rate (95% CI, 98.0%-100.0%), whereas the antibiotics group had a 72.7% success rate (95% CI, 66.8%-78.0%). Given the antibiotic failure rate of 27.3% and the pre-specified noninferiority margin of 24%, this study is unable to demonstrate the noninferiority of antibiotics compared to appendectomy in this patient population. However, it is interesting to note that the majority of patients in the antibiotics group were successfully managed without surgery and thus had a lower complication rate than the appendectomy group. Further studies will need to be done and could focus on aspects such as using a more restrictive approach to antibiotics in order to minimize drug resistance.

Also in the medical news… 

The PermiT multicenter randomized control trial suggests that enteral feeding with full protein intake but moderate nonprotein calories in critically ill patients is not associated with a lower 90-day all-cause mortality compared to standard caloric intake. [10] 

Earlier this week, the FDA announced its decision to ban partially hydrogenated oils (PHOs) from processed foods within the next three years. PHOs are the main source of industrially produced trans fats, which present an increased risk of coronary heart disease and are hence no longer “generally recognized as safe.” [11]

The Middle East respiratory syndrome coronavirus (MERS-CoV) has unfortunately been spreading throughout Asia this past week. It was imported to South Korea by a man who had travelled to the Middle East recently, and was also brought to China by the son of a patient who visited his father in a hospital before traveling to China. [12] Nearly half of the South Koreans diagnosed with MERS visited or took care of patients in the Samsung Medical Center in Seoul. [13] As of June 26th, there was 181 confirmed cases in the Republic of Korea and 1 in China, with 31 confirmed deaths thus far. [14]

Dr. Olivia Begasse De Dhaem is an incoming medical intern at NYU Langone Medical Center

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

Image courtesy of[2]/1/


[1] Sengupta S. 60 Million People Fleeing Chaotic Lands, U.N. Says. New York Times. June 18, 2015.®ion=top-news&WT.nav=top-news

[2] Higgins A. In Testy Debate, E.U. Leaders Fail to Agree on Quotas to Spread Migrants Across Bloc. New York Times June 26, 2015.

[3] Reuters. PM Says Haiti Faces ‘Humanitarian Crisis’ as Thousands Cross Border. New York Times June 26, 2015.

[4] Liptak A. Gay Marriage Backers Win Supreme Court Victory. New York Times June 26, 2015.

[5] Liptak A. Supreme Court Allows Nationwide Health Care Subsidies. New York Times June 25, 2015.

[6] Goodnough A, Tavernise S. Health Law Ruling Elicits Sighs of Relief and Vows to Continue Fighting. New York Times June 25, 2015.

[7] Overton ET, Chan ES, Brown TT, Tebas P, McComsey GA, et al. Vitamin D and Calcium Attenuate Bone Loss With Antiretroviral Therapy Initiation: A Randomized Trial. Ann Intern Med. 2015;162(12):815-824.

[8]Long L, Ormiston ML, Yang X, Southwood M, Gräf S, et al. Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension. Nature Medicine, Advanced Online Publication, 15 June 2015.

[9] Salminen P, Paajanen H, Rautio T, Nordström P, Aarnio M, et al. Antibiotic Therapy vs Appendectomy for Treatment of Uncomplicated Acute Appendicitis: The APPAC Randomized Clinical Trial. JAMA. 2015;313(23):2340-2348.

[10] Arabi YM, Aldawood AS, Haddad SH, Al-Dorzi HM, Tamim HM, et al. Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults. N Engl J Med 2015; 372:2398-2408. June 18, 2015.

[11] FDA Consumer Health Information / U.S. Food and Drug Administration. FDA Cuts Trans Fat in Processed Foods. June 2015.

[12] Su S, Wong G, Liu Y, Gao GF, Li S, et al. MERS in South Korea and China: a potential outbreak threat? The Lancet, Vol 385, Issue 9985, pp2349 – 2350.

[13] Sang-Hun C. South Korean Hospital Scrutinized in MERS Outbreak. New York Times. June 17, 2015.

[14] WHO, global alert and response, Middle East respiratory syndrome coronavirus (MERS-CoV) – Republic of Korea, Disease outbreak news, 26 June 2015.