Medicine JournalFeeds

Stem-cell transplantation for sickle cell disease.

N Engl J Med. 2010 Mar 11;362(10):955-6; author reply 956

Authors: Walters MC, Sullivan KM

PMID: 20225347 [PubMed - in process]

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Insulin regimens in type 2 diabetes.

N Engl J Med. 2010 Mar 11;362(10):959-60; author reply 960

Authors: Margolis KL, O’Connor PJ, Sperl-Hillen JM

PMID: 20225350 [PubMed - in process]

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Biventricular pacing.

N Engl J Med. 2010 Mar 11;362(10):957-8; author reply 958-9

Authors: Lim HS

PMID: 20225349 [PubMed - in process]

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Biventricular pacing.

N Engl J Med. 2010 Mar 11;362(10):957; author reply 958-9

Authors: Tomoda H

PMID: 20225348 [PubMed - in process]

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Insulin regimens in type 2 diabetes.

N Engl J Med. 2010 Mar 11;362(10):960; author reply 960

Authors: Cordido F

PMID: 20225351 [PubMed - in process]

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How to Think about Future Health Care Spending.

N Engl J Med. 2010 Mar 10;

Authors: Fuchs VR

PMID: 20220179 [PubMed - as supplied by publisher]

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Individual Genomes on the Horizon.

N Engl J Med. 2010 Mar 10;

Authors: Lifton RP

PMID: 20220178 [PubMed - as supplied by publisher]

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Whole-Genome Sequencing in a Patient with Charcot-Marie-Tooth Neuropathy.

N Engl J Med. 2010 Mar 10;

Authors: Lupski JR, Reid JG, Gonzaga-Jauregui C, Rio Deiros D, Chen DC, Nazareth L, Bainbridge M, Dinh H, Jing C, Wheeler DA, McGuire AL, Zhang F, Stankiewicz P, Halperin JJ, Yang C, Gehman C, Guo D, Irikat RK, Tom W, Fantin NJ, Muzny DM, Gibbs RA

BACKGROUND: Whole-genome sequencing may revolutionize medical diagnostics through rapid identification of alleles that cause disease. However, even in cases with simple patterns of inheritance and unambiguous diagnoses, the relationship between disease phenotypes and their corresponding genetic changes can be complicated. Comprehensive diagnostic assays must therefore identify all possible DNA changes in each haplotype and determine which are responsible for the underlying disorder. The high number of rare, heterogeneous mutations present in all humans and the paucity of known functional variants in more than 90% of annotated genes make this challenge particularly difficult. Thus, the identification of the molecular basis of a genetic disease by means of whole-genome sequencing has remained elusive. We therefore aimed to assess the usefulness of human whole-genome sequencing for genetic diagnosis in a patient with Charcot-Marie-Tooth disease. METHODS: We identified a family with a recessive form of Charcot-Marie-Tooth disease for which the genetic basis had not been identified. We sequenced the whole genome of the proband, identified all potential functional variants in genes likely to be related to the disease, and genotyped these variants in the affected family members. RESULTS: We identified and validated compound, heterozygous, causative alleles in SH3TC2 (the SH3 domain and tetratricopeptide repeats 2 gene), involving two mutations, in the proband and in family members affected by Charcot-Marie-Tooth disease. Separate subclinical phenotypes segregated independently with each of the two mutations; heterozygous mutations confer susceptibility to neuropathy, including the carpal tunnel syndrome. CONCLUSIONS: As shown in this study of a family with Charcot-Marie-Tooth disease, whole-genome sequencing can identify clinically relevant variants and provide diagnostic information to inform the care of patients. Copyright 2010 Massachusetts Medical Society.

PMID: 20220177 [PubMed - as supplied by publisher]

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Tumor-associated macrophages and survival in classic Hodgkin’s lymphoma.

N Engl J Med. 2010 Mar 11;362(10):875-85

Authors: Steidl C, Lee T, Shah SP, Farinha P, Han G, Nayar T, Delaney A, Jones SJ, Iqbal J, Weisenburger DD, Bast MA, Rosenwald A, Muller-Hermelink HK, Rimsza LM, Campo E, Delabie J, Braziel RM, Cook JR, Tubbs RR, Jaffe ES, Lenz G, Connors JM, Staudt LM, Chan WC, Gascoyne RD

BACKGROUND: Despite advances in treatments for Hodgkin’s lymphoma, about 20% of patients still die from progressive disease. Current prognostic models predict the outcome of treatment with imperfect accuracy, and clinically relevant biomarkers have not been established to improve on the International Prognostic Score. METHODS: Using gene-expression profiling, we analyzed 130 frozen samples obtained from patients with classic Hodgkin’s lymphoma during diagnostic lymph-node biopsy to determine which cellular signatures were correlated with treatment outcome. We confirmed our findings in an independent cohort of 166 patients, using immunohistochemical analysis. RESULTS: Gene-expression profiling identified a gene signature of tumor-associated macrophages that was significantly associated with primary treatment failure (P=0.02). In an independent cohort of patients, we found that an increased number of CD68+ macrophages was correlated with a shortened progression-free survival (P=0.03) and with an increased likelihood of relapse after autologous hematopoietic stem-cell transplantation (P=0.008), resulting in shortened disease-specific survival (P=0.003). In multivariate analysis, this adverse prognostic factor outperformed the International Prognostic Score for disease-specific survival (P=0.003 vs. P=0.03). The absence of an elevated number of CD68+ cells in patients with limited-stage disease defined a subgroup of patients with a long-term disease-specific survival of 100% with the use of current treatment strategies. CONCLUSIONS: An increased number of tumor-associated macrophages was strongly associated with shortened survival in patients with classic Hodgkin’s lymphoma and provides a new biomarker for risk stratification.

PMID: 20220182 [PubMed - in process]

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The missing voice of patients in drug-safety reporting.

N Engl J Med. 2010 Mar 11;362(10):865-9

Authors: Basch E

PMID: 20220181 [PubMed - in process]

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