Biomarker

Galactomannan and PCR versus culture and histology for directing use of antifungal treatment for invasive aspergillosis in high-risk haematology patients: a randomised controlled trial.

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Background

Empirical treatment with antifungal drugs is often used in haematology patients at high risk of invasive aspergillosis. We compared a standard diagnostic strategy (culture and histology) with a rapid biomarker-based diagnostic strategy (aspergillus galactomannan and PCR) for directing the use of antifungal treatment in this group of patients.

Methods

In this open-label, parallel-group, randomised controlled trial, eligible patients were adults undergoing allogeneic stem-cell transplantation or chemotherapy for acute leukaemia, with no history of invasive fungal disease. Enrolled patients were randomly assigned (1:1) by a computer-generated schedule to follow either a standard diagnostic strategy (based on culture and histology) or a biomarker-based diagnostic strategy (aspergillus galactomannan and PCR) to direct treatment with antifungal drugs. Patients, were followed up for 26 weeks or until death. Masking of the use of different diagnostic tests was not possible for patients, treating physicians, or investigators. The primary endpoint was empirical treatment with antifungal drugs in the 26 weeks after enrolment (for the biomarker-based diagnostic strategy, a single postive galactomannan or PCR result was deemed insufficient to confirm invasive aspergillosis, so treatment in this context was classified as empirical). This outcome was assessed by an independent data review committee from which the study allocations were masked. Analyses were by intention to treat and included all enrolled patients. This study is registered withClinicalTrial.gov, number NCT00163722.

Findings

240 eligible patients were recruited from six Australian centres between Sept 30, 2005, and Nov 19, 2009. 122 were assigned the standard diagnostic strategy and 118 the biomarker-based diagnostic strategy. 39 patients (32%) in the standard diagnosis group and 18 (15%) in the biomarker diagnosis group received empirical antifungal treatment (difference 17%, 95% CI 4—26; p=0·002). The numbers of patients who had hepatotoxic and nephrotoxic effects did not differ significantly between the standard diagnosis and biomarker diagnosis groups (hepatotoxic effects: 21 [17%] vs 12 [10%], p=0·11; nephrotoxic effects: 52 [43%] vs 60 [51%], p=0·20).

Interpretation

Use of aspergillus galactomannan and PCR to direct treatment reduced use of empirical antifungal treatment. This approach is an effective strategy for the management of invasive aspergillosis in high-risk haematology patients.

Source: lancet

Tobacco smoke biomarkers and cancer risk among male smokers in the Shanghai Cohort Study.

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Tobacco smoke constituent metabolites are established biomarkers of cigarette smoke exposure. ► This paper demonstrates that some of these metabolites are also biomarkers of cancer risk in male smokers from Shanghai. ► The biomarkers of cancer risk are total cotinine, total NNAL, PheT, and total NNN.

Abstract

Metabolites of tobacco smoke constituents can be quantified in urine and other body fluids providing a realistic measure of carcinogen and toxicant dose in a smoker. Many previous studies have demonstrated that these metabolites – referred to as biomarkers in this paper – are related to tobacco smoke exposure. The studies reviewed here were designed to answer another question: are these substances also biomarkers of cancer risk? Using a prospective study design comparing biomarker levels in cancer cases and controls, all of whom were smokers, the results demonstrate that several of these biomarkers – total cotinine, total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), r-1-,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), and total N′-nitrosonornicotine (NNN) – are biomarkers of cancer risk. Therefore, these biomarkers have the potential to become part of a cancer risk prediction algorithm for smokers.

 

Source: cancer letters

 

 

 

Inflammasome proteins in cerebrospinal fluid of brain-injured patients as biomarkers of functional outcome.

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Traumatic brain injury (TBI), the third most common CNS pathology, plagues 5.3 million Americans with permanent TBI-related disabilities. To evaluate injury severity and prognosis, physicians rely on clinical variables. Here, the authors seek objective, biochemical markers reflecting molecular injury mechanisms specific to the CNS as more accurate measurements of injury severity and outcome. One such secondary injury mechanism, the innate immune response, is regulated by the inflammasome, a molecular platform that activates caspase-1 and interleukin-1β.

Methods

The authors investigated whether inflammasome components were present in the CSF of 23 patients with TBI and whether levels of inflammasome components correlate with outcome. The authors performed an immunoblot analysis of CSF samples from patients who suffered TBI and nontrauma controls and assessed the outcomes 5 months postinjury by using the Glasgow Outcome Scale. Data were analyzed using Mann-Whitney U-tests and linear regression analysis.

Results

Patients with severe or moderate cranial trauma exhibited significantly higher CSF levels of the inflammasome proteins ASC, caspase-1, and NALP-1 than nontrauma controls (p < 0.0001, p = 0.0029, and p = 0.0202, respectively). Expression of each protein correlated significantly with the Glasgow Outcome Scale score at 5 months postinjury (p < 0.05). ASC, caspase-1, and NALP-1 were significantly higher in the CSF of patients with unfavorable outcomes, including death and severe disability (p < 0.0001).

Conclusions

NALP-1 inflammasome proteins are potential biomarkers to assess TBI severity, outcome, and the secondary injury mechanisms impeding recovery, serving as adjuncts to clinical predictors.

Source: Journal of Neurosurgery

 

 

 

 

Screening halves breast cancer deaths.

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Women who undergo screening halve their risk of dying from breast cancer, a new study from the University of Melbourne has found.

The study, published in Cancer Epidemiology, Biomarkers and Prevention is the largest of its kind in Australia and one of the largest in the world. It followed about 4,000 women in a study of the BreastScreen program in Western Australia.

University of Melbourne Research Fellow Dr Carolyn Nickson and colleagues from the Melbourne School of Population Health said the findings reaffirmed the importance and efficacy of mammography.

The study focused on women aged 50-69 years, who are in the target age range for screening. It included 427 cases where women had died from breast cancer and 3,650 control women who were still alive when the other women died.

The research team compared screening attendance between the two groups and found screening was much lower among women who had died from breast cancer, a finding that is consistent with a similar study from South Australia and with numerous studies from around the world. Comparison with similar studies showed an average estimate of a 49 per cent reduced risk of dying.

Some other studies including studies from Australia claim that screening doesn’t reduce risk of dying from breast cancer. However, these studies do not compare outcomes for individual women.

“Sound research methods have been used in this study. I believe it is time to move on from the debate about whether screening reduces mortality and to instead direct research resources to help improve the program for women who choose to use it,” Dr Nickson said.

“It is important that Australian women have accurate information about the pros and cons of participating in BreastScreen. The findings of this study may help women decide whether to participate.”

“Early detection is the key to early treatment and the free BreastScreen program is the best health service available to detect breast cancers earlier in women aged 50-69 years.”

Source: Science Alert