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See detailA Highly Durable RNAi Therapeutic Inhibitor of PCSK9
LANCELLOTTI, Patrizio ULiege; Oury, Cécile ULiege

in New England Journal of Medicine (2017), 376

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See detailKidney-Failure Risk Projection for the Living Kidney-Donor candidate.
DELANAYE, Pierre ULiege; Glassock, Richard

in New England Journal of Medicine (2016), 374(21), 2093-2094

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See detailPredictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia.
Zeisler, Harald; Llurba, Elisa; CHANTRAINE, Frédéric ULiege et al

in New England Journal of Medicine (2016), 374(1), 13-22

BACKGROUND: The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is elevated in pregnant women before the clinical onset of preeclampsia, but its predictive value in ... [more ▼]

BACKGROUND: The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is elevated in pregnant women before the clinical onset of preeclampsia, but its predictive value in women with suspected preeclampsia is unclear. METHODS: We performed a prospective, multicenter, observational study to derive and validate a ratio of serum sFlt-1 to PlGF that would be predictive of the absence or presence of preeclampsia in the short term in women with singleton pregnancies in whom preeclampsia was suspected (24 weeks 0 days to 36 weeks 6 days of gestation). Primary objectives were to assess whether low sFlt-1:PlGF ratios (at or below a derived cutoff) predict the absence of preeclampsia within 1 week after the first visit and whether high ratios (above the cutoff) predict the presence of preeclampsia within 4 weeks. RESULTS: In the development cohort (500 women), we identified an sFlt-1:PlGF ratio cutoff of 38 as having important predictive value. In a subsequent validation study among an additional 550 women, an sFlt-1:PlGF ratio of 38 or lower had a negative predictive value (i.e., no preeclampsia in the subsequent week) of 99.3% (95% confidence interval [CI], 97.9 to 99.9), with 80.0% sensitivity (95% CI, 51.9 to 95.7) and 78.3% specificity (95% CI, 74.6 to 81.7). The positive predictive value of an sFlt-1:PlGF ratio above 38 for a diagnosis of preeclampsia within 4 weeks was 36.7% (95% CI, 28.4 to 45.7), with 66.2% sensitivity (95% CI, 54.0 to 77.0) and 83.1% specificity (95% CI, 79.4 to 86.3). CONCLUSIONS: An sFlt-1:PlGF ratio of 38 or lower can be used to predict the short-term absence of preeclampsia in women in whom the syndrome is suspected clinically. (Funded by Roche Diagnostics.). [less ▲]

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See detailGigantism, acromegaly, and GPR101 mutations.
Daly, Adrian ULiege; Trivellin, Giampaolo; Stratakis, Constantine

in New England Journal of Medicine (2015), 372(13), 1265

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See detailFracture risk and zoledronic acid therapy in men with osteoporosis
Boonen, S.; REGINSTER, Jean-Yves ULiege; Kaufman, J.-M. et al

in New England Journal of Medicine (2012), 367(18), 1714-1723

BACKGROUND: Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk ... [more ▼]

BACKGROUND: Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1199 men with primary or hypogonadism-associated osteoporosis who were 50 to 85 years of age to receive an intravenous infusion of zoledronic acid (5 mg) or placebo at baseline and at 12 months. Participants received daily calcium and vitamin D supplementation. The primary end point was the proportion of participants with one or more new morphometric vertebral fractures over a period of 24 months. RESULTS: The rate of any new morphometric vertebral fracture was 1.6% in the zoledronic acid group and 4.9% in the placebo group over the 24-month period, representing a 67% risk reduction with zoledronic acid (relative risk, 0.33; 95% confidence interval, 0.16 to 0.70; P = 0.002). As compared with men who received placebo, men who received zoledronic acid had fewer moderate-to-severe vertebral fractures (P = 0.03) and less height loss (P = 0.002). Fewer participants who received zoledronic acid had clinical vertebral or nonvertebral fractures, although this difference did not reach significance because of the small number of fractures. Bone mineral density was higher and bone-turnover markers were lower in the men who received zoledronic acid (P<0.05 for both comparisons). Results were similar in men with low serum levels of total testosterone. The zoledronic acid and placebo groups did not differ significantly with respect to the incidence of death (2.6% and 2.9%, respectively) or serious adverse events (25.3% and 25.2%). CONCLUSIONS: Zoledronic acid treatment was associated with a significantly reduced risk of vertebral fracture among men with osteoporosis. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00439647.) Copyright © 2012 Massachusetts Medical Society. [less ▲]

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See detailDyspnea and stress testing
PIERARD, Luc ULiege; Lancellotti, Patrizio ULiege

in New England Journal of Medicine (2006), 354(8), 871-872

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See detailAutoantibodies to folate receptors in the cerebral folate deficiency syndrome
Ramaekers, Vincent ULiege; Rothenberg, S. P.; Sequeira, J. M. et al

in New England Journal of Medicine (2005), 352(19), 1985-1991

In infantile-onset cerebral folate deficiency, 5-methyltetrahydrofolate (5MTHF) levels in the cerebrospinal fluid are low, but folate levels in the serum and erythrocytes are normal. We examined serum ... [more ▼]

In infantile-onset cerebral folate deficiency, 5-methyltetrahydrofolate (5MTHF) levels in the cerebrospinal fluid are low, but folate levels in the serum and erythrocytes are normal. We examined serum specimens from 28 children with cerebral folate deficiency, 5 of their mothers, 28 age-matched control subjects, and 41 patients with an unrelated neurologic disorder. Serum from 25 of the 28 patients and 0 of 28 control subjects contained high-affinity blocking autoantibodies against membrane-bound folate receptors that are present on the choroid plexus. Oral folinic acid normalized 5MTHF levels in the cerebrospinal fluid and led to clinical improvement. Cerebral folate deficiency is a disorder in which autoantibodies can prevent the transfer of folate from the plasma to the cerebrospinal fluid. Copyright © 2005 Massachusetts Medical Society. [less ▲]

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See detailThe role of ischemic mitral regurgitation in the pathogenesis of acute pulmonary edema
Pierard, Luc ULiege; Lancellotti, Patrizio ULiege

in New England Journal of Medicine (2004), 351(16), 1627-1634

BACKGROUND: Acute mitral regurgitation may cause pulmonary edema, but the pathogenetic role of chronic ischemic mitral regurgitation, a dynamic condition, has not yet been characterized. METHODS: We ... [more ▼]

BACKGROUND: Acute mitral regurgitation may cause pulmonary edema, but the pathogenetic role of chronic ischemic mitral regurgitation, a dynamic condition, has not yet been characterized. METHODS: We prospectively studied 28 patients (mean [+/-SD] age, 65+/-11 years) with acute pulmonary edema and left ventricular systolic dysfunction and 46 patients without a history of acute pulmonary edema. The two groups were matched for all baseline characteristics. Patients underwent quantitative Doppler echocardiography during exercise. Exercise-induced changes in the left ventricular volume, the ejection fraction, the mitral regurgitant volume, the effective regurgitant orifice area, and the transtricuspid pressure gradient were compared in patients with and without acute pulmonary edema. RESULTS: The two groups had similar clinical and baseline echocardiographic characteristics. They also had similar exercise-induced changes in heart rate, systolic blood pressure, and left ventricular volumes. In the univariate analysis, patients with recent pulmonary edema had a much higher increase than did the patients without pulmonary edema in mitral regurgitant volume (26+/-14 ml vs. 5+/-14 ml, P<0.001), the effective regurgitant orifice area (16+/-10 mm(sup 2) vs. 2+/-9 mm(sup 2), P<0.001), and the transtricuspid pressure gradient (29+/-10 mm Hg vs. 13+/-11 mm Hg, P<0.001). In the multivariate analysis, exercise-induced changes in the effective regurgitant orifice area (P<0.001), in the transtricuspid pressure gradient (P=0.001), and in the left ventricular ejection fraction (P=0.02) were independently associated with a history of recent pulmonary edema. CONCLUSIONS: In patients with left ventricular systolic dysfunction, acute pulmonary edema is associated with the dynamic changes in ischemic mitral regurgitation and the resulting increase in pulmonary vascular pressure. [less ▲]

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See detailThe effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis
Meunier, Pierre J.; Roux, Christian; Seeman, Ego et al

in New England Journal of Medicine (2004), 350(5), 459-468

BACKGROUND: Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that ... [more ▼]

BACKGROUND: Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. METHODS: To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months. RESULTS: New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P<0.001 for both comparisons). There were no significant differences between the groups in the incidence of serious adverse events. CONCLUSIONS: Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures. [less ▲]

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See detailTransmission of chronic myeloid leukemia through peripheral-blood stem-cell transplantation.
Baron, Frédéric ULiege; DRESSE, Marie-Françoise ULiege; Beguin, Yves ULiege

in New England Journal of Medicine (2003), 349(9), 913-4

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See detailImages in Clinical Medicine. A Medical Mystery: Alkaptonuric ochronosis
Nikkels, Arjen ULiege; Pierard, Gérald ULiege

in New England Journal of Medicine (2001), 344(21), 1642-1643

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