Journals

Disruptive Behaviors Among Physicians.

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Disruptive Behaviors Among Physicians.

JAMA. 2014 Aug 21;

Authors: Sanchez LT

PMID: 25144182 [PubMed - as supplied by publisher]

Anti-interleukin 4 and 13 for asthma treatment in the era of endotypes.

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Anti-interleukin 4 and 13 for asthma treatment in the era of endotypes.

Curr Opin Allergy Clin Immunol. 2014 Aug 19;

Authors: Kau AL, Korenblat PE

Abstract

PURPOSE OF REVIEW: To summarize recent advances in IL-4 and IL-13 blockade in the treatment of asthma.

RECENT FINDINGS: Historically, anticytokine therapies have historically been unsuccessful in the treatment of asthma because of the heterogeneity of its pathogenesis. Recent advances in our understanding of asthma pathophysiology and our increased ability to phenotype patients have led to the identification of asthmatic subsets (endotypes) that are most likely to respond to anticytokine therapy. Several new biologic therapies targeting IL-13 or both IL-4 and IL-13 signaling are currently in clinical trials and both types of therapies have demonstrated therapeutic benefit.

SUMMARY: Anti-IL-4/13 therapies, guided by knowledge of an individual’s underlying pathophysiology, are a promising class of therapies for treatment of asthma.

PMID: 25144263 [PubMed - as supplied by publisher]

Cockroach allergy and allergen-specific immunotherapy in asthma: potential and pitfalls.

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Cockroach allergy and allergen-specific immunotherapy in asthma: potential and pitfalls.

Curr Opin Allergy Clin Immunol. 2014 Aug 19;

Authors: Bassirpour G, Zoratti E

Abstract

PURPOSE OF REVIEW: To provide a summary and discussion of cockroach allergy and clinical trials of cockroach allergen immunotherapy.

RECENT FINDINGS: Cockroach allergen exposure among sensitized children is increasingly recognized as a key factor contributing to asthma morbidity. Recent trials suggest that cockroach immunotherapy holds promise as a treatment strategy with studies demonstrating immunomodulatory and clinical effects. However, a few obstacles need to be overcome to realize the full potential of this treatment modality as cockroach-allergic patients often exhibit complex sensitization patterns to multiple cockroach-associated proteins, and an immunodominant allergen has not been identified. These factors have made it difficult to produce standardized cockroach allergen extracts that are potent and provide the broad allergen profiles needed for optimal treatment. There have been important advances in the identification and cloning of cockroach allergens, and several strategies are being developed to provide therapeutic cockroach allergen products with enhanced clinical efficacy.

SUMMARY: Allergen immunotherapy has the capability of modulating the immune response to cockroach allergen and has potential as a valuable treatment modality. Further studies of the clinical efficacy, along with the development of improved therapeutic products, are needed to advance our knowledge and realize the full potential of this promising therapy.

PMID: 25144264 [PubMed - as supplied by publisher]

Ebola Vaccination: If Not Now, When?

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Ebola Vaccination: If Not Now, When?

Ann Intern Med. 2014 Aug 21;

Authors: Galvani AP, Ndeffo-Mbah ML, Wenzel N, Childs JE

PMID: 25141813 [PubMed - as supplied by publisher]

Ebola Fever: Reconciling Ebola Planning With Ebola Risk in U.S. Hospitals.

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Ebola Fever: Reconciling Ebola Planning With Ebola Risk in U.S. Hospitals.

Ann Intern Med. 2014 Aug 21;

Authors: Klompas M, Diekema DJ, Fishman NO, Yokoe DS

PMID: 25141883 [PubMed - as supplied by publisher]

Tuberculin skin test negativity is under tight genetic control of the chromosomal region 11p14-15 in settings of different TB endemicity.

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Tuberculin skin test negativity is under tight genetic control of the chromosomal region 11p14-15 in settings of different TB endemicity.

J Infect Dis. 2014 Aug 20;

Authors: Cobat A, Poirier C, Hoal E, Boland-Auge A, de La Rocque F, Corrard F, Grange G, Migaud M, Bustamante J, Boisson-Dupuis S, Casanova JL, Schurr E, Alcaïs A, Delacourt C, Abel L

Abstract

A substantial proportion of subjects exposed to a contagious tuberculosis (TB) case display lack of tuberculin skin test (TST) reactivity. We previously mapped a major locus (TST1) controlling lack of TST reactivity in families from a South-African hyperendemic TB area. Here we conducted a household TB contact study in a French low endemic TB area. A genome-wide analysis of TST negativity identified a significant linkage signal (p<3×10(-5)) in close vicinity of TST1. Combined analysis of the two samples increased evidence of linkage (p=2.4×10(-6)), further implicating genetic factors located on 11p14-15. This region overlaps the TNF1 locus controlling mycobacteria-driven TNF-α production.

PMID: 25143445 [PubMed - as supplied by publisher]

The Invisible Issue of Organ Laundering.

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The Invisible Issue of Organ Laundering.

Transplantation. 2014 Aug 20;

Authors: Manzano A, Monaghan M, Potrata B, Clayton M

Abstract

Global institutions, although suggesting measures to deter organ trafficking, reiterate the lack of official statistics about this illegal trade. In this article, we explore the reasons why organ trafficking remains unreported. We argue that the complex factors that perpetuate invisibility facilitate trafficked organs being “laundered” in the health care systems of the purchaser’s country, hindering accurate estimation of the problem. The factors are as follows: (a) issues of globalization, jurisdiction, and law enforcement; (b) the power of health care professionals; (c) the reimbursement of transplantation costs abroad by insurers; (d) ambivalence of the victim status of the sellers; and (e) the buyers as vulnerable offenders.

PMID: 25144445 [PubMed - as supplied by publisher]

Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants.

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Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants.

Gut. 2014 Aug 20;

Authors: Jaeggi T, Kortman GA, Moretti D, Chassard C, Holding P, Dostal A, Boekhorst J, Timmerman HM, Swinkels DW, Tjalsma H, Njenga J, Mwangi A, Kvalsvig J, Lacroix C, Zimmermann MB

Abstract

BACKGROUND: In-home iron fortification for infants in developing countries is recommended for control of anaemia, but low absorption typically results in >80% of the iron passing into the colon. Iron is essential for growth and virulence of many pathogenic enterobacteria. We determined the effect of high and low dose in-home iron fortification on the infant gut microbiome and intestinal inflammation.

METHODS: We performed two double-blind randomised controlled trials in 6-month-old Kenyan infants (n=115) consuming home-fortified maize porridge daily for 4 months. In the first, infants received a micronutrient powder (MNP) containing 2.5 mg iron as NaFeEDTA or the MNP without iron. In the second, they received a different MNP containing 12.5 mg iron as ferrous fumarate or the MNP without the iron. The primary outcome was gut microbiome composition analysed by 16S pyrosequencing and targeted real-time PCR (qPCR). Secondary outcomes included faecal calprotectin (marker of intestinal inflammation) and incidence of diarrhoea. We analysed the trials separately and combined.

RESULTS: At baseline, 63% of the total microbial 16S rRNA could be assigned to Bifidobacteriaceae but there were high prevalences of pathogens, including Salmonella Clostridium difficile, Clostridium perfringens, and pathogenic Escherichia coli. Using pyrosequencing, +FeMNPs increased enterobacteria, particularly Escherichia/Shigella (p=0.048), the enterobacteria/bifidobacteria ratio (p=0.020), and Clostridium (p=0.030). Most of these effects were confirmed using qPCR; for example, +FeMNPs increased pathogenic E. coli strains (p=0.029). +FeMNPs also increased faecal calprotectin (p=0.002). During the trial, 27.3% of infants in +12.5 mgFeMNP required treatment for diarrhoea versus 8.3% in -12.5 mgFeMNP (p=0.092). There were no study-related serious adverse events in either group.

CONCLUSIONS: In this setting, provision of iron-containing MNPs to weaning infants adversely affects the gut microbiome, increasing pathogen abundance and causing intestinal inflammation.

TRIAL REGISTRATION NUMBER: NCT01111864.

PMID: 25143342 [PubMed - as supplied by publisher]

A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration.

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A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration.

Gut. 2014 Aug 20;

Authors: King LY, Canasto-Chibuque C, Johnson KB, Yip S, Chen X, Kojima K, Deshmukh M, Venkatesh A, Tan PS, Sun X, Villanueva A, Sangiovanni A, Nair V, Mahajan M, Kobayashi M, Kumada H, Iavarone M, Colombo M, Fiel MI, Friedman SL, Llovet JM, Chung RT, Hoshida Y

Abstract

OBJECTIVE: The number of patients with HCV-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression.

DESIGN: We developed a prognostic index, comprised of a 186-gene signature validated in our previous genome-wide profiling study, bilirubin (>1 mg/dL) and platelet count (<100 000/mm(3)), in an Italian HCV cirrhosis cohort (training cohort, n=216, median follow-up 10 years). The gene signature test was implemented using a digital transcript counting (nCounter) assay specifically developed for clinical use and the prognostic index was evaluated using archived specimens from an independent cohort of HCV-related cirrhosis in the USA (validation cohort, n=145, median follow-up 8 years).

RESULTS: In the training cohort, the prognostic index was associated with hepatic decompensation (HR=2.71, p=0.003), overall death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child-Turcotte-Pugh class (HR=6.70, p<0.001). The patients in the validation cohort were stratified into high-risk (16%), intermediate-risk (42%) or low-risk (42%) groups by the prognostic index. The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), overall death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001) and all liver-related adverse events (HR=4.98, p<0.001).

CONCLUSIONS: A genomic and clinical prognostic index readily available for clinical use was successfully validated, warranting further clinical evaluation for prognostic prediction and clinical trial stratification and enrichment for preventive interventions.

PMID: 25143343 [PubMed - as supplied by publisher]

Oral antiviral therapy for HBeAg negative chronic hepatitis B: better stop or continue?

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Oral antiviral therapy for HBeAg negative chronic hepatitis B: better stop or continue?

Gut. 2014 Aug 20;

Authors: Lampertico P

PMID: 25143344 [PubMed - as supplied by publisher]