Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
N Engl J Med [journal]
- Clone Wars - The Emergence of Neoplastic Blood-Cell Clones with Aging. [JOURNAL ARTICLE]
- N Engl J Med 2014 Nov 26.
Blood cells originate from hematopoietic stem cells (HSCs). HSCs are infrequent (<2 per 10(8) bone marrow cells, or about 11,000 to 22,000 per person) and rarely divide.(1),(2) Because mutations occur with DNA replication during cell division, HSC quiescence maximizes genomic stability and thus safety. Mutations, however, can and do occur. Most are innocuous and do not substantially alter protein quantities or structure. Some make subtle changes that contribute to cellular diversity and allow HSCs or their offspring to react efficiently to differing environmental stresses. However, if a mutation speeds HSC self-renewal divisions or slows apoptosis, this results in more . . .
- Chimpanzee Adenovirus Vector Ebola Vaccine - Preliminary Report. [JOURNAL ARTICLE]
- N Engl J Med 2014 Nov 26.
Background The unprecedented 2014 epidemic of Ebola virus disease (EVD) has prompted an international response to accelerate the availability of a preventive vaccine. A replication-defective recombinant chimpanzee adenovirus type 3-vectored ebolavirus vaccine (cAd3-EBO), encoding the glycoprotein from Zaire and Sudan species that offers protection in the nonhuman primate model, was rapidly advanced into phase 1 clinical evaluation. Methods We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO. Twenty healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2×10(10) particle units or 2×10(11) particle units. Primary and secondary end points related to safety and immunogenicity were assessed throughout the first 4 weeks after vaccination. Results In this small study, no safety concerns were identified; however, transient fever developed within 1 day after vaccination in two participants who had received the 2×10(11) particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2×10(11) particle-unit dose than in the group that received the 2×10(10) particle-unit dose (geometric mean titer against the Zaire antigen, 2037 vs. 331; P=0.001). Glycoprotein-specific T-cell responses were more frequent among those who received the 2x10(11) particle-unit dose than among those who received the 2×10(10) particle-unit dose, with a CD4 response in 10 of 10 participants versus 3 of 10 participants (P=0.004) and a CD8 response in 7 of 10 participants versus 2 of 10 participants (P=0.07). Conclusions Reactogenicity and immune responses to cAd3-EBO vaccine were dose-dependent. At the 2×10(11) particle-unit dose, glycoprotein Zaire-specific antibody responses were in the range reported to be associated with vaccine-induced protective immunity in challenge studies involving nonhuman primates. Clinical trials assessing cAd3-EBO are ongoing. (Funded by the Intramural Research Program of the National Institutes of Health; VRC 207 ClinicalTrials.gov number, NCT02231866 .).
- Sodium Zirconium Cyclosilicate in Hyperkalemia. [JOURNAL ARTICLE]
- N Engl J Med 2014 Nov 21.
Background Hyperkalemia (serum potassium level, >5.0 mmol per liter) is associated with increased mortality among patients with heart failure, chronic kidney disease, or diabetes. We investigated whether sodium zirconium cyclosilicate (ZS-9), a novel selective cation exchanger, could lower serum potassium levels in patients with hyperkalemia. Methods In this multicenter, two-stage, double-blind, phase 3 trial, we randomly assigned 753 patients with hyperkalemia to receive either ZS-9 (at a dose of 1.25 g, 2.5 g, 5 g, or 10 g) or placebo three times daily for 48 hours. Patients with normokalemia (serum potassium level, 3.5 to 4.9 mmol per liter) at 48 hours were randomly assigned to receive either ZS-9 or placebo once daily on days 3 to 14. The primary end point was the exponential rate of change in the mean serum potassium level at 48 hours. Results At 48 hours, the mean serum potassium level had decreased from 5.3 mmol per liter at baseline to 4.9 mmol per liter in the group of patients who received 2.5 g of ZS-9, 4.8 mmol per liter in the 5-g group, and 4.6 mmol per liter in the 10-g group, for mean reductions of 0.5, 0.5, and 0.7 mmol per liter, respectively (P<0.001 for all comparisons) and to 5.1 mmol per liter in the 1.25-g group and the placebo group (mean reduction, 0.3 mmol per liter). In patients who received 5 g of ZS-9 and those who received 10 g of ZS-9, serum potassium levels were maintained at 4.7 mmol per liter and 4.5 mmol per liter, respectively, during days 3 to 15, as compared with a level of more than 5.0 mmol per liter in the placebo group (P<0.01 for all comparisons). Rates of adverse events were similar in the ZS-9 group and the placebo group (12.9% and 10.8%, respectively, in the initial phase; 25.1% and 24.5%, respectively, in the maintenance phase). Diarrhea was the most common complication in the two study groups. Conclusions Patients with hyperkalemia who received ZS-9, as compared with those who received placebo, had a significant reduction in potassium levels at 48 hours, with normokalemia maintained during 12 days of maintenance therapy. (Funded by ZS Pharma; ClinicalTrials.gov number, NCT01737697 .).
- A New Era for the Treatment of Hyperkalemia? [JOURNAL ARTICLE]
- N Engl J Med 2014 Nov 21.
The potassium concentration within human cells is approximately 70 mmol per liter, yet extracellular potassium concentration is normally 3.5 to 5.0 mmol per liter.(1),(2) Hyperkalemia is defined as a plasma potassium level of greater than 5.0 mmol per liter. Mild hyperkalemia (>5.0 to 5.9 mmol per liter) requires monitoring and the avoidance of a high intake of potassium and, often, changing therapies that may be increasing potassium levels. Greater degrees of hyperkalemia - potassium levels of 6.0 to 7.0 mmol per liter (moderate hyperkalemia) and more than 7.0 mmol per liter (marked hyperkalemia) - may lead to cardiac arrhythmias . . .
- Patiromer in Patients with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors. [JOURNAL ARTICLE]
- N Engl J Med 2014 Nov 21.
Background Hyperkalemia increases the risk of death and limits the use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) in high-risk patients. We assessed the safety and efficacy of patiromer, a nonabsorbed potassium binder, in a multicenter, prospective trial. Methods Patients with chronic kidney disease who were receiving RAAS inhibitors and who had serum potassium levels of 5.1 to less than 6.5 mmol per liter received patiromer (at an initial dose of 4.2 g or 8.4 g twice a day) for 4 weeks (initial treatment phase); the primary efficacy end point was the mean change in the serum potassium level from baseline to week 4. Eligible patients at the end of week 4 (those with a baseline potassium level of 5.5 to <6.5 mmol per liter in whom the level decreased to 3.8 to <5.1 mmol per liter) entered an 8-week randomized withdrawal phase in which they were randomly assigned to continue patiromer or switch to placebo; the primary efficacy end point was the between-group difference in the median change in the serum potassium level over the first 4 weeks of that phase. Results In the initial treatment phase, among 237 patients receiving patiromer who had at least one potassium measurement at a scheduled visit after day 3, the mean (±SE) change in the serum potassium level was -1.01±0.03 mmol per liter (P<0.001). At week 4, 76% (95% confidence interval, 70 to 81) of the patients had reached the target potassium level (3.8 to <5.1 mmol per liter). Subsequently, 107 patients were randomly assigned to patiromer (55 patients) or placebo (52 patients) for the randomized withdrawal phase. The median increase in the potassium level from baseline of that phase was greater with placebo than with patiromer (P<0.001); a recurrence of hyperkalemia (potassium level, ≥5.5 mmol per liter) occurred in 60% of the patients in the placebo group as compared with 15% in the patiromer group through week 8 (P<0.001). Mild-to-moderate constipation was the most common adverse event (in 11% of the patients); hypokalemia occurred in 3%. Conclusions In patients with chronic kidney disease who were receiving RAAS inhibitors and who had hyperkalemia, patiromer treatment was associated with a decrease in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemia. (Funded by Relypsa; OPAL-HK ClinicalTrials.gov number, NCT01810939 ).
- Testicular Cancer - Discoveries and Updates. [JOURNAL ARTICLE]
- N Engl J Med 2014 Nov 20.
Testicular Cancer - Discoveries and Updates Review Article, N Engl J Med 2014;371:2005-2016. In the final sentence of the Relapsed Disease section (page 2013), ". . . ifosfamide plus cisplatin . . ." should have been ". . . ifosfamide plus paclitaxel . . .." The article is correct at NEJM.org.
- Images in clinical medicine. Corkscrew esophagus. [Journal Article]
- N Engl J Med 2014 Nov 20; 371(21):e33.
- Videos in clinical medicine. Reduction of pulled elbow. [Journal Article]
- N Engl J Med 2014 Nov 20; 371(21):e32.
- Mitotane for 21-hydroxylase deficiency in an infertile man. [Letter, Research Support, Non-U.S. Gov't]
- N Engl J Med 2014 Nov 20; 371(21):2042-4.
- Donor activating KIR2DS1 in leukemia. [Comment, Letter]
- N Engl J Med 2014 Nov 20; 371(21):2042.