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Archive for March 3, 2013

‘Wrong’ immune response aids TB

TB in a patient's lung

Tuberculosis attacks the lungs


Some bacteria, including tuberculosis, are able to invade because the body launches the ‘wrong’ immune response, say researchers.

Instead of fighting off tuberculosis, people with a severe infection produce a protein which attacks viruses, the journal Science reports.

About 8.7 million people are infected with tuberculosis every year.

The findings may explain why viruses can make people more susceptible to bacterial infections.

A spring peak in tuberculosis infections may be linked to the effects of viruses circulating in winter, experts suggested.

US researchers first identified the phenomenon using leprosy – which is caused by a similar bacterium to tuberculosis.

Looking at skin lesions in leprosy patients, the team found that two different immune proteins were present.

In those with a milder form of the disease, they found a protein associated with a bacterial immune response – interferon-gamma.

Whereas in patients with a more serious form of leprosy, a protein associated with a viral response – interferon-beta – was prominent.

Further work showed the genes for interferon-beta – the virus-fighting protein – were more frequently expressed in the blood of tuberculosis patients with more severe disease.

In disguise

The researchers said in those with severe disease, the body was responding as if it was attacking a virus, enabling the bacteria to remain hidden and replicate unchallenged within cells.

Not only is interferon-beta an ineffective weapon against bacteria, it can block the action of interferon gamma – which is when bacteria can gain a foothold, the researchers said.

In the face of a real viral infection it may mean that the attention of the immune system is diverted letting a bacterial infection in.

Prof Robert Modlin, a dermatology and microbiology expert at the University of California, Los Angeles, said the study raises the possibility that a decrease or increase of one of these two proteins could shift the balance from mild to more serious disease.

“We may find that therapeutic interventions to block or enhance specific interferon responses may be an effective strategy to alter the balance in favour of protection against bacterial diseases.”

The results may also help to explain why outbreaks of tuberculosis in winter such as one currently spreading among homeless groups in Los Angeles are quick to take hold.

A potent combination of people sleeping in close quarters in shelters, flu outbreaks diverting the body’s immune response to the viral setting and a lack of vitamin D from sunlight, which also impacts the immune response, may be to blame, they suggested.

“With TB on the rise, this scenario could play out not only in cities in the United States but all over the world,” Prof Modlin said.

Prof Ajit Lalvani, director of the Tuberculosis Research Unit at Imperial College London said there is a spring peak in rates of tuberculosis which have been attributed to low levels of vitamin D.

“But this shows there could be at least one other reason – that other viral infections are leading some months down the line to progression from latent to active TB disease.

“The timing fits, but that remains to be proven.”


Late-stage breast cancer survival ‘lower in UK’

A mammography of a woman's breast

More women in the UK had missing information about the stage of their cancer at diagnosis

Women with late-stage breast cancer have lower survival rates in the UK than five other high-income countries, including Sweden and Canada, suggests a study in the British Journal of Cancer.

In the UK, 28% of women with the most advanced cancers survived for three years, compared with 42% in Sweden.

Researchers looked at more than 250,000 women diagnosed between 2000 and 2007.

Cancer Research UK questioned whether women were receiving the best treatment.

The study, carried out by the International Cancer Benchmarking Partnership, investigated whether international differences in survival could be explained by delays in diagnosis.

Led by researchers at the London School of Hygiene and Tropical Medicine, the study analysed data on women from Australia, Canada, Denmark, Norway and Sweden up to three years after diagnosis.

For all stages of breast cancer, the study found that three-year survival was 87-89% in the UK and Denmark, and 91-94% in the other four countries.

We know that UK women diagnosed with breast cancer are not routinely given CT scans to check if the disease has spread.”

Sara HiomCancer Research UK

One-year survival varied less, from 94.3% in the UK to 98.4% in Sweden.

But for women with the most advanced breast cancers, one-year survival ranged from 53% in the UK to 67% in Sweden – and there was still a 14% difference between the UK and Sweden in three-year survival for those with late-stage breast cancer.

In the UK, similar proportions of women were diagnosed in the early stages as in most of the other countries. One year after diagnosis, survival for women with early-stage breast cancer was close to 100% in all six countries.

It was only for women with late-stage breast cancer that survival percentages were lower in the UK.

This suggests that lower overall breast cancer survival in the UK is not because women are being diagnosed at a later stage than in other countries, the study says.

Missing information

In Denmark, only 30% of women with breast cancer were diagnosed at an early stage, compared with 42-45% elsewhere.

This suggests that low overall breast cancer survival in Denmark – the only country that had not fully implemented a national breast screening programme before 2007 – was due to women being diagnosed at a later stage of disease.

Generally, women eligible for screening (typically 50-69-year-olds) are diagnosed at an earlier stage than younger and older women.

The UK also had the highest proportion of women with missing information about their stage at diagnosis.

The study also found that international differences in survival were also wider for older women.

Three-year survival was 4% higher in Sweden (96%) than in the UK (92%) for women aged 50-69, but for women aged 70 years or more, the difference was 12% (Sweden 91% compared with 79% in the UK).

These findings suggest that older women with breast cancer and women with more advanced disease may be treated less aggressively in the UK than in the other five countries.

Dr Sarah Walters, lead author from the Cancer Research UK Cancer Survival Group at the London School of Hygiene and Tropical Medicine, said the reasons for low overall survival in the UK and Denmark were different and needed different solutions.

“The roll-out of national mammography screening will be expected to improve overall survival in Denmark.

“In the UK, we should now investigate whether the treatment of women with later-stage breast cancer meets international standards. There is particular concern that this is not the case, especially for older women.”

Sara Hiom, Cancer Research UK’s director of early diagnosis, said international comparisons were useful in helping to understand what was influencing cancer survival.

“We’re beginning to see some important clues now, but while we’re closing the survival gap for breast cancer, UK women continue to fare worse than in these other countries.

“We know that UK women diagnosed with breast cancer are not routinely given CT scans to check if the disease has spread, which could mean we aren’t always accurately staging more advanced disease.

But we also need to investigate the possibility that fewer women with later stage breast cancer in the UK receive the best treatment for their circumstances.”

Eluned Hughes, head of public health at Breakthrough Breast Cancer, said: “If breast cancer survival rates matched the best in Europe, 1,000 extra lives would be saved in England alone, so work to bridge the gap is crucial.”


Skin cancer ‘able to fight off body’s immune system’

Skin cancer

A deadly form of skin cancer is able to fend off the body’s immune system, UK researchers have found.

Analysis of tumour and blood samples shows that melanoma knocks out the body’s best immune defence.

A potential test could work out which patients are likely to respond to treatment, the Journal of Clinical Investigation reports.

Cancer Research UK said the body’s response was a “complex puzzle”.

Previous work from the team at King’s College London showed that while patients with melanoma produced antibodies that could attack tumour cells, the immune system often seemed powerless to stop the cancer progressing.

But in the latest research they discovered that the subtype of antibody attracted by the melanoma cells was the most ineffective at mounting the right sort of response.

In samples from 80 melanoma patients they say that the conditions created by the tumour attract IgG4 antibodies, which mount the weakest response and in turn interfere with any “strong” IgG1 antibodies that might be present.

Continue reading the main story

“Start Quote

This work is still at an early stage, but it’s a step towards developing more effective treatments for skin cancer”

Dr Kat ArneyCancer Research UK

By mimicking the conditions created by melanomas, they showed that in the presence of tumour cells, the immune system sent out IgG4 antibodies, but when faced with healthy cells it functioned as expected with IgG1 circulating.

They also confirmed that IgG4 was ineffective in launching an immune attack against cancer cells.

Potential test

In additional tests in 33 patients, they found that those with higher levels of the weak antibody IgG4 had a less favourable prognosis compared with those with levels nearer to normal.

Study author Dr Sophie Karagiannis said: “This work bears important implications for future therapies since not only are IgG4 antibodies ineffective in activating immune cells to kill tumours but they also work by blocking antibodies from killing tumour cells.”

She said not only was IgG4 stopping the patient’s more powerful antibodies from eradicating cancer, but it could also explain why some treatments based on boosting the immune response may be less effective in some patients.

Co-author Prof Frank Nestle said more work was needed on developing IgG4 as a potential test to improve patient care by helping to identify patients most likely to respond to treatments.

“This study can also inform the rational design of novel strategies to counteract IgG4 actions,” he added.

Dr Kat Arney, science communications manager at Cancer Research UK, said: “There’s a lot we don’t yet understand about how our immune system recognises and responds to cancer, so we’re pleased to have supported this new research that’s helping to solve such a complex puzzle.

“This work is still at an early stage, but it’s a step towards developing more effective treatments for skin cancer and potentially other types of cancer in the future.”


Many nurses ‘feel discouraged’ from raising care concerns

NHS staff
More than half of those who said they had spoken out said their concerns had been ignored

Many nurses believe the NHS has a culture that discourages staff from raising concerns about patient care, a survey suggests.

Almost 30% of 800 nurses polled by Nursing Times magazine said being seen as a troublemaker was the biggest barrier to them speaking out.

Inaction by managers was cited as a barrier by 23%.

The government said it had taken measures to support whistle-blowers and was considering further action.

The survey was sent out to the magazine’s database of nurses and was conducted online.

Some 84% of respondents to the poll said they had raised concerns about a colleague’s practice or attitude.

A total of 23% of the nurses said they had done so “several times” or “regularly”, and 23% “at least once”.

But of those who had raised concerns, 52% said there had been no appropriate outcome after they had spoken out and a similar percentage said they had faced negative consequences as a result of doing so.

‘Ostracised and bullied’

The poll comes after the public inquiry into the failings at Stafford Hospital – run by Mid Staffordshire NHS Trust – highlighted a lack of support for nurses who tried to raise concerns.

The inquiry report by Robert Francis QC argued for “fundamental change” in the culture of the NHS to make sure patients were put first.

We are determined that staff who have the courage and integrity to speak out in the interests of patient safety are protected and listened to”

Dan PoulterHealth minister

Nursing Times editor Jenni Middleton said: “If we want to make sure Mid Staffs does not happen again, we must welcome the input of staff and ensure they are heard, without fear of reprisal.”

She added: “I have personally spoken to nurses who, having raised concerns, have been sidelined and ostracised by their employers, bullied and marginalised by their colleagues – and end up feeling ashamed and guilty, as well as concerned that their careers are over.

“Regulation plays its part, of course, but the ability of staff to spot what’s going on is irreplaceable in ensuring that the NHS is a safe NHS.”

Dr Peter Carter, chief executive of the Royal College of Nursing, said: “It is extremely worrying that a large number of nurses still feel their concerns are going unheard, even worse that some have to live with the threat of reprisal.”

Dean Royles, chief executive of the NHS Employers organisation, said that while there had been “enormous efforts” by employers to encourage staff to speak out “we need to do more to build their confidence that they can voice concerns in safety”.

‘Duty of openness’

Health minister Dan Poulter said: “We are determined that staff who have the courage and integrity to speak out in the interests of patient safety are protected and listened to.

“We have already taken a range of measures to protect and support whistleblowers in the NHS, including funding a national helpline, embedding rights in their employment contracts and issuing new guidance in partnership with trades unions and employers.”

He said a new “contractual duty of openness” would apply to the NHS organisations from April when dealing with patients.

He added that ministers were also considering whether they needed to “go further” in the wake of the Stafford Hospital report.


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