Study: can a few cherries a day keep gout away?

Cherries may no longer be just for topping off ice-cream sundaes - a U.S. study of people with gout linked eating the fruit with a 35 percent to 75 percent lower risk of having an attack.

Doctors have reported that some patients recommend cherries to prevent gout attacks, but the connection has only been studied a few times before, said lead researcher Yuqing Zhang, a professor at the Boston University School of Medicine.

"These findings suggest that cherry intake is associated with a lower risk of gout attacks," Zhang and colleagues wrote in the journal Arthritis & Rheumatism.

But Zhang warned that the study does not prove that cherries alone prevent gout attacks, and that patients should stick with their present gout medications.

"They can go out and eat the cherries, but they shouldn't abandon their medical treatment at all," Zhang added.

Gout arises with uric acid crystals build up in the joints. The body produces uric acid when it breaks down purines - substances found naturally in the body but also in certain foods, like organ meats, anchovies, mushrooms and some seafoods.

For the study, Zhang and his colleagues recruited patients over the Internet to take online surveys about their attacks.

All the 633 participants had had a gout attack in the last 12 months, had been diagnosed with gout by a doctor, lived in the United States and were at least 18 years old. They also had to release their medical records to the researchers.

For the next year, the patients filled out surveys every time they had an attack. The survey asked about symptoms, the drugs used in treatment and about certain risk factors, including what they had eaten.

The patients also took similar surveys at the beginning of the study, and every three months when it was underway.

Of the 633 patients, 224 said they had eaten fresh cherries during the year, 15 said they had consumed cherry extract and 33 had both.

During the year, the researchers collected information on 1,247 gout attacks, which works out to about two per patient.

Overall, the researchers found that eating cherries over a given two-day period was linked to a 35 percent decrease in the risk of having a gout attack during that period, compared to not eating cherries.

Consuming cherry extract was tied to a 45 percent risk reduction, and eating both fresh cherries and extract was tied to a 37 percent lower risk.

The biggest reduction, though, came with eating fresh cherries while taking the anti-gout medication allpurinol (Lopurin, Zyloprim.) That combination was linked to a 75 percent reduction in risk.

Researchers say there are a few possible reasons. One is that vitamin C, which is found in cherries, can influence the amount of uric acid in a person's blood, according to Allan Gelber, who co-wrote an editorial accompanying the study.

NEW ANTIBIOTIC FOR DRUG RESISTANT INFECTION

 A new potential class of antibiotics called LpxC inhibitors was recently found to block the ability of bacteria to initiate the septic cascade, saving mice from lethal infection, although agents did not kill the bacteria in vitro, as is the typical mechanism of action of antibiotics.

Senior author, Brad Spellberg, MD, from the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and the David Geffen School of Medicine, Los Angeles, California, and colleagues report their findings in an article published online October 2 in mBio.

"Traditionally, people have tried to find antibiotics that rapidly kill bacteria," noted Dr. Spellberg in an American Society for Microbiology news release. "But we found a new class of antibiotics which has no ability to kill Acinetobacter that can still protect, not by killing the bug, but by completely preventing it from turning on host inflammation."

Acinetobacter baumannii is a Gram-negative bacillus (GNB) that is one of the most drug-resistant pathogens in the United States and around the world. Strains of the bacterium have become resistant to every US Food and Drug Administration–approved antibiotic; thus, infections caused by this bacterium can be untreatable, and as a result the risk for in-hospital mortality for A baumannii infections is among the highest of all GNB.

The researchers first compared wild-type mice with toll-like receptor 4 (TLR-4)-deficient mice and found that TLR-4 deficient mice were highly resistant to lethal infection, whereas 100% of wild-type mice died from infection. This indicated a role for TLR-4 and an inflammatory immune response in the lethal effects of the bacteria. Surprisingly, despite the fact that wild-type mice had 100% mortality and TLR4-deficient mice had no mortality, there was no significant difference between the 2 groups in bacteria burden. Thus, the lethality of infection was not related to how much bacteria were present but, rather, to how much host inflammation occurred in response to infection.

A baumannii is also known to express lipopolysaccharide (LPS) on its surface, which binds to TLR4 and thereby induces host production of inflammatory cytokines, such as tumor necrosis factor and interleukin 6. According to the researchers, more-virulent strains of A baumannii shed more LPS than less-virulent strains, which prompted them to investigate whether LpxC-1, an inhibitor of LpxC, an enzyme involved in LPS synthesis, could affect the pathogenicity of A baumannii.

The researchers report that LpxC-1 treatment did not kill the bacteria in vitro, but treatment with LpxC-1 did suppress LPS levels in A baumannii in vitro and in vivo in mice during infection. As a result, the treated infected mice also showed decreased markers of inflammation (P < .01) and a higher survival rate (100% vs 0% compared with the placebo group at 72 hours).

"Since there are few if any drugs in development with the potential to treat lethal [drug-resistant] A baumanniiinfections, the discovery that an entirely new class of compounds has therapeutic potential is of great potential clinical importance," the authors write.

Block Organism's Lethal Action

"Unlike traditional antibiotics, LpxC-1 doesn't kill the bacteria, it just shuts down the manufacture of the endotoxin and stops the body from mounting the inflammatory immune response to it that is the actual cause of death," Dr. Spellberg told Medscape Medical News.

He adds, "Resistance is caused by us trying to kill bacteria, and bacteria not wanting to die." Traditional antibiotic screens seek to find antibiotics that rapidly kill bacteria, which creates selective pressure that drives antibiotic resistance. Finding antibiotics that do not kill the bacteria but, rather, prevent them from causing illness is a new and important direction to take to find treatments for highly resistant infections and has the promise of driving resistance more slowly.

"There's a growing movement in infectious disease therapy to control the host inflammation response in treatment rather than just 'murdering' the organism," Liise-anne Pirofski, MD, from the Albert Einstein College of Medicine in New York City, and a reviewer of the study for mBio, stated in the news release. She adds, "This is a very elegant and important validation that this approach can work — at least in mice."

In an independent comment to Medscape Medical News, Jian Li, PhD, from Monash University's Institute of Pharmaceutical Sciences in Parkville, Victoria, Australia, stated that this study supports the idea that even though the LPS inhibitor LpxC-1 itself does not kill bacterial cells, treatment with LpxC-1 reduced immunopathogenesis, thereby enhancing bacterial killing by the immune system.

"This approach is similar to antivirulence compounds (eg, Quorum sensing inhibitors), which don't kill bacterial cells but make bacterial cells less virulent. It is generally believed that such approaches may not lead to development of resistance," Dr. Li told Medscape Medical News.

According to Dr. Li, "clearly more preclinical and clinical studies are required, and "it is important to examine if, like traditional antibiotics, resistance to LPS inhibition would emerge after suboptimal treatment with LPS inhibitors," he said.

"We believe it is important to combine anti-immunopathogenic compounds (eg, LPS inhibitors) with traditional antibiotics, an approach which would not only kill bacterial cells but also make bacterial cells less virulent and pathogenic, thereby enhancing clearance by the immune system."

Financial support was received from the National Institute of Allergy and Infectious Diseases and from Pfizer. Several authors report that they are employed by Pfizer and one author receives support from the Canadian Institutes for Health Research. Dr. Li has disclosed no relevant financial relationships.

ESMO 2012-SIGLE OR COMBINATION CHEMOTHERAPY IN SARCOMA?

A large trial comparing single and combination chemotherapy in the first-line treatment of soft tissue sarcoma failed to meet its primary overall survival end point. However, the results were of borderline significance, and secondary end points favored the combination, so was the trial really negative?

This was the question raised here at the 2012 European Society for Medical Oncology Congress by one commentator.

Speaking at a Best of ESMO summary session, Alessandro Gronchi, MD, a surgical oncologist from the Instituto Nazionale Tumori in Milan, Italy, suggested that the results can be interpreted as providing evidence for both treatment options.

In the palliative setting, single-agent chemotherapy with doxorubicin should be used, he said. However, if there is a chance of cure or if a reduction of tumor size is needed to improve symptoms and quality of life, then the combination of doxorubicin plus ifosfamide should be used, he said.

Although there have been several previous trials comparing single and combination chemotherapy, none have given a definitive answer, he noted.

There has been a lot of transatlantic and transcultural debate about which is the best first-line option, explained study author Winette van der Graaf, MD, from Radboud University Medical Center in Nijmegen, the Netherlands. This is the reason her team conducted this large randomized phase 3 study.

The trial, conducted by the European Organization for Research and Treatment of Cancer (EORTC), involved 455 patients recruited from 9 countries. Patients had grade 2 or 3 advanced or metastatic soft tissue sarcoma, and were 18 to 60 years of age.

Both of these factors are notable, said George Demetri, MD, from the Dana-Farber Cancer Center in Boston, Massachusetts, who was not involved with the study. He noted that sarcoma is disproportionately common in children, and in adults sarcoma is more common in the elderly. He explained that all sarcomas are of mesenchymal origin but that they cover a very broad range of different histologic subtypes.

Single vs Combo Chemotherapy

Patients were randomized to receive doxorubicin (75 mg/m² as a bolus or 72-hour infusion) either alone or in combination with ifosfamide (10 g/m² over 4 days with the colony-stimulating factor pegfilgrastim), and were treated every 3 weeks until disease progression or the completion of 6 cycles of therapy.

After a median follow-up of 56 months, there was no significant difference in median overall survival, the primary end point, between the combination and single-agent groups (14.3 vs 12.8; hazard ratio [HR], 0.83; P = .0076).

Secondary end points were significantly better with the combination. Median progression-free survival was 7.4 months with the combination and 4.6 months with the single agent (HR, 0.74; P = .003). Most of this effect was seen in patients 40 to 50 years of age, Dr. van der Graaf noted. In addition, the overall response rate with the combination was double that with doxorubicin alone (26.5% vs 13.6%).

However, the combination was "considerably more toxic," Dr. van der Graaf said. Grade 3 or higher adverse events reported in the combination and single-agent groups included febrile neutropenia (45.9% vs 13.5%), leucopenia (43.3% vs 17.9%), anemia (34.9% vs 19.7%), and thrombocytopenia (33.5% vs 0.4%).

The lack of significant survival results means that single-agent doxorubicin remains the standard treatment for first-line use, Dr. van der Graaf concluded.

However, she noted that "if surgery for unresectable tumors or (curative) metastasectomy is foreseen, combination therapy can be considered."

"In highly symptomatic disease in patients without comorbidity, combination treatment is optional. The pros and cons should, as always, be discussed with the patients," she said, adding that "this is easier now that we have the results of this study."

Poor Prognosis

Dr. Demetri reminded the audience that metastatic soft tissue sarcomas have variable clinical behaviors, but they are nearly all incurable. "Therefore, our intention is to palliate and prolong life with the highest possible quality," he explained.

The median survival for these patients is about 1 year, he said. In this study, after 1 year, 60% of patients in the combination group were still alive, compared with 51% in the single-agent group. During the first year of the study, there was some divergence between the 2 curves, he noted; disease control was longer with the combination than with doxorubicin alone (7.4 vs 5.0 months). For a patient who may have only 1 year to live, there is a chance that more of that time will be disease-free when treated with the combination, he said.

Dr. Demetri concluded that, in his opinion, if a patient is asymptomatic, the best first-line therapy remains single-agent doxorubicin. However, if a patient is symptomatic or if tumor shrinkage is required because the tumor is causing pain, then he would suggest using the combination of doxorubicin plus ifosfamide.

But there is another option, he reminded the audience; the targeted agent pazopanib (Votrient) was approved for use in sarcoma in April in the United States and in August in Europe.

"This is an important step," Dr. Demetri explained in a previous interview, because it offers an alternative to chemotherapy. Pazopanib is an oral drug with a milder adverse-effect profile, and might be preferable for patients who have small asymptomatic tumors, he said.

Can it! Soda studies cite stronger link to obesity

As Americans debate what is most to blame for the nation's obesity epidemic, researchers say they have the strongest evidence yet that sugary drinks play a leading role and that eliminating them would, more than any other single step, make a huge difference.
Three studies published Friday in the New England Journal of Medicine represent the most rigorous effort yet to see if there is a link between sugar-sweetened beverages and expanding U.S. waistlines.
"I know of no other category of food whose elimination can produce weight loss in such a short period of time," said Dr. David Ludwig, director of the New Balance Foundation Obesity Prevention Center at Boston Children's Hospital, who led one of the studies. "The most effective single target for an intervention aimed at reducing obesity is sugary beverages."
Previous research on the subject has been mixed, and beverage makers fiercely contest the idea that a single source of daily calories can bear so much responsibility.
"We know, and science supports, that obesity is not uniquely caused by any single food or beverage," said the American Beverage Association (ABA) in a statement. "Studies and opinion pieces that focus solely on sugar-sweetened beverages, or any other single source of calories, do nothing meaningful to help address this serious issue."
The NEJM studies, as well as an editorial and opinion pieces on the topic of sugary drinks and obesity, land as concern about obesity and its impact on public health is rising.
A report released this week projected that at least 44 percent of U.S. adults could be obese by 2030, compared to 35.7 percent today, bringing an extra $66 billion a year in obesity-related medical costs.
Last week, New York City adopted a regulation banning the sale of sugary drinks in containers larger than 16 ounces at restaurants and other outlets regulated by the city health department.
Sugary drinks are in the crosshairs because from 1977 to 2002 the number of calories Americans consumed from them doubled, government data show, making them the largest single source of calories in the diet. Adult obesity rates, 15 percent in the late 1970s, more than doubled in that period. The ABA points out, however, that consumption has since fallen, yet obesity rates keep rising.
Although most observational studies find that people who drink sugary beverages are more likely to be obese than people who do not, no cause-and-effect has been proved. People who drink sugary beverages, especially children, also watch more TV and eat more calorie-dense fast food, raising the possibility that liquid sugar is not the main culprit.
A 2008 analysis of 12 studies, led by a scientist who went on to work for the ABA, concluded that the association between sugary drinks and body-mass index (BMI) "was near zero."
Studies in which children cut their intake of sugary drinks found modest benefits, but "they were considered unconvincing," said Martijn Katan of VU University in Amsterdam: "Most had a small number of subjects and followed them for only a short time." He and his colleagues aimed to do better.
BUILDING A BETTER STUDY
For DRINK (Double-Blind Randomized Intervention in Kids), they gave 641 children aged about 5 to 12 and with a healthy BMI of just under 17 one 8-ounce (250 milliliter) noncarbonated drink per day, sweetened artificially or with sugar. The sugar-free drinks were specially formulated to look and taste like sugary ones so the kids would not know which they had.
About a quarter of the kids stopped drinking the beverages. Among those who stuck it out for 18 months, the sugar-free kids gained less body fat, 2.2 pounds (1 kilogram) less weight, and 0.36 units less BMI than the sugary-drink kids, the researchers report in the NEJM.
Why? There is good evidence that liquid sugar does not produce a feeling of fullness that other calories do. "When children substituted a sugar-free drink, their bodies did not sense the absence of calories, and they did not replace them with other food or drinks," said Katan.
DRINK doesn't answer whether switching to zero-calorie drinks would help obese kids. But another study in the same issue of NEJM suggests it might.
Researchers at Boston Children's had zero-calorie drinks delivered to 110 obese 15-year-olds who had BMIs of about 30 (where obesity starts), counseled them not to drink sugary beverages and offered other support.
After a year the teens had cut their intake of sugary drinks from almost two a day to zero and their daily calorie intake by 454. They had gained an average of 3.5 pounds (1.6 kilograms). By comparison, 114 teens who continued to consume sugar-sweetened beverages gained 7.7 pounds (3.5 kg) on average and ten times the BMI units: 0.63 compared to 0.06.
Once the deliveries stopped the two groups diverged less. After two years, teens who had received the no-cal drink deliveries had gained 9.5 pounds (4.3 kg) and 0.71 unit of BMI, compared to the control group's 11.2 pounds (5.5 kg) and 1.0 unit of BMI.
"It isn't surprising that after the intervention stopped, old behaviors crept back," said Ludwig of the New Balance Center. An "obesogenic" environment that promotes calorie-laden foods "overwhelms individuals' ability to maintain behavioral change" such as avoiding sugary drinks.
Hispanic teens benefited the most: Those receiving no-cal deliveries gained 14 fewer pounds after one year and almost 20 fewer pounds after two. That raised the possibility that genetic factors influence the effect of sugary drinks.
To investigate gene-environment-obesity links, scientists at Harvard School of Public Health looked at 33,097 people from long-term ongoing health studies, such as the Nurses' Health Study, identifying how many sugary drinks they consume and whether they have any of 32 genes linked to obesity.
The effect of genes on the likelihood of becoming obese was twice as large among people who drank one or more sugary drinks per day as among those who had less than one a month, the scientists report in the NEJM. In other words, belting back soda and sugary tea may turbocharge the genetic risk of obesity.
Conversely, eating a healthy diet devoid of sugary drinks keeps fat genes inactive. People with "fat genes" can be thinner if they avoid sugary drinks and other high-calorie foods.

CANCER ON THE RISE IN PREGNANT WOMEN

NEW YORK (Reuters Health) Sep 19 - The number of pregnant women diagnosed with cancer has increased over the past couple of decades, a new study from Australia suggests.

In 2007, the most recent year studied, researchers found 192 out of every 100,000 pregnant and postpartum women received a cancer diagnosis - up from 112 per 100,000 women in 1994.

Researchers couldn't determine what was behind that increase in risk, but said it could be due in part to the older average age of expectant moms combined with better cancer detection.

Another explanation could be "the increased interaction with health services during pregnancy," said Dr. Christine Roberts, an obstetrics researcher at the University of Sydney who worked on the study.

Dr. Roberts said some doctors in her department had seen a few cases of expectant moms with cancer and wanted to know whether this was indicative of any increase in risk.

To try to answer that question, her group collected information from three large databases on births, cancer cases and hospital admissions in New South Wales, Australia. They had data on roughly 780,000 women who gave birth more than 1.3 million times between 1994 and 2008.

During the same period, there were about 1,800 new cancers diagnosed in pregnant women and those who'd given birth within the last year.

As diagnoses became more common over the years, pregnant women also got older, on average, the researchers noted in the obstetrics and gynecology journal BJOG.

For example, in 1994, 13% of pregnant women were over age 35, compared to almost 24% in 2007.

The risk of cancer is known to increase with age - and 35-plus women in the study were over three times more likely to get cancer compared to those under 30 in 2007. But age only accounted for a fraction of the increased cancer risk over time, the researchers found.

Dr. Lloyd Smith, who treats gynecologic cancers at the University of California, Davis, agreed that improved detection likely accounts for some portion of the increase in cases.

He pointed out that melanoma was the most common cancer diagnosed, affecting 45 out of every 100,000 pregnant or postpartum women.

Australia claims the highest rate of melanoma diagnoses in the world.

Given increasing awareness of the problem of melanoma in Australia, "they probably also have ramped up their surveillance of melanoma, so they're going to detect more," Dr. Smith, who wasn't involved in the new study, told Reuters Health.

Dr. Roberts said that despite the increase in cancer risk, it is still considered a rare event among pregnant or postpartum women.

Women in the study with cancer were more likely to plan an early birth, but "importantly there was no evidence of harm to the babies of women with cancer - they were not at increased risk of reduced growth or death," Dr. Roberts wrote in an email to Reuters Health.

She said more research on cancer treatments for pregnant women is needed.

Dr. Smith said that in his experience, treating pregnant patients has been extremely difficult. "When you have a pregnant woman who has cancer, the infant's at risk, the woman's at risk, the family is in extreme distress and they're seeking the best advice, which is often confused because no one knows quite what to do," he said.

One recent study found that chemotherapy does not appear to harm the fetus, while planning an early delivery to avoid chemo exposure to the baby is actually more risky (see Reuters report of September 27, 2011).