Discovery of hormone essential for iron supply

US researchers have discovered a new hormone that regulates the iron supply needed for the production of red blood cells. According to a study published in "Nature Genetics", the erythroferrone hormone is produced by red blood-cell progenitors in the bone marrow.

Stimulating the production of erythrocytes increases the release of erythroferrone. Subsequently, the hormone regulates the hormone hepcidin, which controls the absorption of iron from food and its distribution in the body. The higher the erythroferrone level, the higher the likelihood that hepcidin is blocked, which, in turn, makes more iron available for the production of red blood cells.

Both too much as well as too little iron can make a person ill. "Modulating the activity of erythroferrone could be a viable strategy for the treatment of iron disorders of both overabundance and scarcity", explained senior author Tomas Ganz from the University of California, Los Angeles.

The discovery may lead to treatments of other diseases associated with anaemia, such as chronic kidney disease, rheumatic disorders or inflammatory diseases. Under these conditions, hepcidin is increased due to inflammation, whereby the iron is practically "locked up". Erythroferrone, or drugs that have the same effect, could suppress hepcidin and thereby make more iron available for the production of red blood cells.

Tomado de Univadis.com

Ref: Nature Genetics 46, 678–684 (2014)

Cortical bone microstructure, tibia density deficits seen with type 2 diabetes, high HbA1c

Type 2 diabetes and increased HbA1c are associated with deficits in cortical bone microstructure and bone density at the distal tibia, according to research presented at the American Society for Bone and Mineral Research 2014 Annual Meeting
Although it is still uncertain whether the cortical bone deficits explain increased lower leg fracture risks seen in patients with diabetes, the findings identify target areas to investigate the mechanism responsible for skeletal fragility.

“Diabetic bone may be characterized by specific deficits to cortical bone, which are not captured by traditional DXA bone mineral density tests,” Elizabeth J. Samelson, PhD, of the Institute for Aging Research at Hebrew SeniorLife, Harvard Medical School,

amelson and colleagues conducted a community-based study involving 627 adults (367 women, 260 men; mean age, 65 years) to compare bone microarchitecture by high-resolution peripheral quantitative computed tomography (HRpQCT) in patients with type 2 diabetes (31 women, 40 men) and healthy individuals and determine relationships with HbA1c.

Participants, all from the Framingham Offspring Cohort, were evaluated for type 2 diabetes and had HbA1c measured at baseline; diabetes was defined as glucose >126 mg/dl or use of diabetes medication. They all underwent HRpQCT scanning at the tibia and radius at 6 years.

The researchers used linear regression to calculate means and correlations for the association between volumetric bone mineral density (vBMD), geometry and microstructure indices of trabecular and cortical bone and type 2 diabetes and HbA1C. Adjustments were made for age, sex and weight. 

Patients with type 2 diabetes exhibited higher numbers than healthy patients at the tibia for

total vBMD (291.06 mg/cm3 vs. 284 .53 mg/ cm3), trabecular vBMD (184.13 mg/cm3 vs. 175.09 mg/cm3) and trabecular number (2.15 1/mm vs. 2.07 1/mm); the differences were not significant.

Conversely, patients with type 2 diabetes demonstrated significantly lower numbers than healthy patients for cortical vBMD (796.74 mg/cm3 vs. 814 mg/cm3) and cortical porosity (11.17% vs. 10.03%).

Similar results were seen with increasing HbA1c, with trabecular indices better with higher levels but cortical bone indices worse; the significance was limited to trabecular number.
No other differences were seen in HRpQCT bone indices between groups or based on HbA1c level. At the radius, no significant associations were seen between bone HRpQCT indices and type 2 diabetes or HbA1C.

“Older adults with type 2 diabetes have increased risk of fracture but higher bone mass density than those without diabetes,” Samelson said. “ If deficits to cortical bone explain increased skeletal fragility in type 2 diabetes, then future therapies that target cortical bone strength can reduce fracture risk in this vulnerable and growing population.” — by Allegra Tiver

For more information: Samelson E. Abstract 1083. Presented at: American Society for Bone and Mineral Research 2014 Annual Meeting; Sept. 12-15, 2014; Houston.

Tomado de http://www.healio.com/endocrinology/bone-mineral-metabolism

Cannabis use in adolescence has negative impact on education

A study looks to add more fuel to the heated debate around the use of marijuana, as researchers have linked the frequent use of cannabis among adolescents with reduced educational attainment. The study also links frequent use of the drug with other negative health outcomes, such as suicide attempts.


The study's lead author, Dr. Edmund Silins, says that the results "provide strong evidence that the prevention or delay of cannabis use is likely to have broad health and social benefits."

The team, comprised of researchers from Australia and New Zealand, received funding from the Australian Government National Health and Medical Research Council, and the study has been published in The Lancet Psychiatry.


Many researchers are pushing for cannabis to be used in a therapeutic capacity, as a form of pain relief or to alleviate symptoms of conditions such as multiple sclerosis (MS) and post-traumatic stress disorder(PTSD).

However, study author Richard Mattick believes that moves toward the decriminalization and legalization of cannabis also contribute toward "raising the possibility that the drug might become more accessible to young people."

Outside of legal avenues, cannabis is the most widely used illicit drug worldwide. The National Institute on Drug Abuse (NIDA) report that around 7% of US high-school seniors are daily or near-daily cannabis users, with around 46% having tried the drug at some point during their lifetime.

Although the study uses data from adolescents in Australia and New Zealand, the authors state that the rates of cannabis use are similar across high-income countries. For example, they cite that the rates of cannabis use among adults in Australia and New Zealand are 10% and 15% respectively, compared with a rate of 15% in the US.

Does early cannabis use compromise education?

For the study, the researchers utilized the data of 3,765 participants from three large, long-term longitudinal studies, tracking cannabis use alongside several developmental outcomes from before the age of 17 up to the age of 30.

They recorded the frequency of cannabis use as never, less than monthly, monthly or more, weekly or more, or daily. The researchers chose to record the following developmental outcomes:

• Cannabis dependence
• Completing high school
• Depression
• Obtaining a university degree
• Suicide attempts
• Use of other illicit drugs
• Welfare dependence.

The researchers found significant associations between the frequency of adolescent cannabis use and all of the designated developmental outcomes. After adjusting for potential confounding factors such as socioeconomic status and mental illness, they found that five of the associations remained significant.

Individuals who had used cannabis daily before the age of 17 were 60% less likely to complete high school or obtain a degree than those who had never used cannabis. They were also 18 times more likely to become dependent on cannabis, eight times more likely to use other illicit drugs and seven times more likely to attempt suicide by the age of 25.

Most significantly, the researchers found that the risk of negative developmental outcomes increased relative to the frequency of the cannabis dose. Daily cannabis users experienced the strongest effects of the association.

Impact on reforming legislation


In a linked commentary, Prof. Merete Nordentoft, of the University of Copenhagen, Denmark, explains why these results may have occurred:

"Persistent cannabis use has adverse effects, such as low energy and initiative, and impairment of cognitive functions, and these factors are likely to mediate the harmful effect of cannabis on educational attainment."

The authors say that these findings are consistent with the results of previous studies investigating early cannabis use alongside these developmental outcomes. They suggest that preventing or delaying cannabis use in adolescents could have far-reaching benefits, both socially and with regard to health.

One measure that the authors suggest could be implemented is screening for cannabis use in adolescents as standard practice during visits to doctors, child psychiatrists, school nurses and other health care practitioners. This is due to an estimated lack of self-reporting among adolescent cannabis users.

"Efforts to reform cannabis legislation should be carefully assessed to ensure they reduce adolescent cannabis use and prevent potentially adverse effects on adolescent development," says Dr. Silins.

In spite of this, the authors also acknowledge that within US states where cannabis has been made increasingly available for medical use, there has been no reported increase in use among young people.

The study still urges caution. The landscape is undeniably changing with regard to how cannabis is perceived and utilized, and the authors believe that as this framework changes, the needs of the youth must always be considered in order to prevent adverse developmental outcomes.

Tomado de: Medical News Today. Written by James McIntosh

Inflammatory marker signals diabetic nephropathy development

Measuring serum levels of high-sensitivity C-reactive protein (hs-CRP) could help to predict which patients with Type 2 diabetes will develop renal disease, research suggests.

Results of a prospective cohort study conducted in Japan show that patients with the highest hs-CRP levels were more likely to develop microalbuminuria than those with the lowest levels.

Over a median follow-up of 0.94 years, 197 patients developed diabetic nephropathy, with an incidence ratio of 155.4 per 1000 person–years. Adjusted hazard ratios (HR) for the risk of developing nephropathy associated with the second, third and fourth hs-CRP quartiles versus the first quartile were 1.31, 1.55 and 1.57, respectively.

However, hs-CRP levels did not appear to be associated with the progression from microalbuminuria to macroalbuminuria. During the same follow-up period, 109 patients experienced diabetic nephropathy progression, with an incidence ratio of 92.4 per 1000 patient–years. Adjusted HRs were 0.59, 1.14 and 1.03, respectively, for the lowest versus the second, third and fourth highest quartiles of hs-CRP, respectively.

“Our study identifies new information regarding CRP and disease outcomes”, observe Yasuaki Hayashino, from Tenri Hospital in Nara, Japan, and co-authors.

“There is a temporal association between elevated levels of hs-CRP and the subsequent risk of developing, not progressing, diabetic nephropathy”, they write in Diabetes Care, adding that this association is seen “even after adjusting for possible confounders, including medication use which may influence the natural course of renal function.”

Longitudinal data on 2518 patients with Type 2 diabetes were obtained from the Diabetes Distress and Care Registry at Tenri study to look at the association between baseline hs-CRP and subsequent risk of development or progression of diabetic nephropathy at 1 year.

Development of diabetic nephropathy was defined as the transition from normoalbuminuria (urinary albumin-to-creatinine ratio [UACR]  menor 3.4 mg/mmol) to microalbuminuria (UACR 3.4–33.9 mg/mmol), and progression as the transition from microalbuminuria to macroalbuminuria (UACR mayor o igual a33.9 mg/mmol).

Hayashino et al note that their results were obtained from studying patients seen at a single diabetes centre in Japan, and so it remains to be seen if they apply to multi-ethnic populations in North American and Europe.

“More research is needed to examine if there is an effective strategy to reduce the risk of diabetic nephropathy in a group of patients with diabetes and elevated levels of hs-CRP”, they conclude.

Tomado de:medwireNews (www.medwirenews.com

Noninvasive DNA Test for Colorectal Cancer Gets FDA Thumbs-up

Among cancers that affect both men and women, colorectal cancer is the third most common cancer and the second leading cause of cancer-related death in the United States, according to the CDC. The agency estimates that if everyone age 50 or older participated in recommended colorectal cancer screening(www.cdc.gov), at least 60 percent of colorectal cancer deaths could be avoided.

Now, family physicians and other clinicians have a singular new option for detecting this life-threatening condition. Moreover, CMS has already laid the groundwork for Medicare coverage for the test.

On Aug. 11, the FDA approved Cologuard, a stool-based colorectal screening test that detects red blood cells and DNA mutations that can indicate the presence of abnormal, possibly precancerous growths, according to an FDA news release(www.fda.gov). It is the first fecal DNA test for colorectal cancer to receive the agency's thumbs-up; previous candidates have lacked adequate sensitivity and specificity.

Specifically, Cologuard detects hemoglobin and mutations associated with colorectal cancer in DNA of cells shed by advanced adenomas as stool moves through the large intestine and rectum. Patients who receive a positive test result are advised to undergo a diagnostic colonoscopy.

"This approval offers patients and physicians another option to screen for colorectal cancer," said Alberto Gutierrez, Ph.D., director of the Office of In Vitro Diagnostics and Radiological Health at the FDA's Center for Devices and Radiological Health (CDRH), in the news release. "Fecal blood testing is a well-established screening tool, and the clinical data showed that (Cologuard) detected more cancers than a commonly used fecal occult test."

The FDA's approval of Madison, Wisc.-based Exact Sciences' Cologuard expands the options for colorectal cancer screening but does not change current related guidelines. The U.S. Preventive Services Task Force (USPSTF) does not recommend stool DNA testing as a method to screen for colorectal cancer. The USPSTF's current screening recommendation(www.uspreventiveservicestaskforce.org) for average-risk adults ages 50 to 75 calls for using fecal occult blood testing (FOBT), sigmoidoscopy or colonoscopy.

However, the USPSTF currently is reviewing its colorectal cancer screening recommendations; evaluation of fecal DNA screening was specifically included in the systematic evidence review(www.ncbi.nlm.nih.gov) the task force is using to inform that update.

Cologuard Study

A recent study(www.nejm.org) published in the New England Journal of Medicineexamined the safety and effectiveness of Cologuard, screening almost 10,000 asymptomatic participants ages 50 to 84 who were at average risk for colorectal cancer and were scheduled to undergo a screening colonoscopy. The trial compared Cologuard to fecal immunochemical testing (FIT).

Compared with FIT, Cologuard was more accurate in detecting colorectal cancers (92 percent versus 74 percent) and advanced adenomas (42 percent versus 24 percent). It was less accurate than FIT, however, at correctly identifying subjects negative for colorectal cancer or advanced adenomas (87 percent versus 95 percent).

Family physician Richard Wender, M.D., who is chair of the National Colorectal Cancer Roundtable and chief cancer control officer for the American Cancer Society (ACS), told AAFP News he was impressed with the sensitivity of Cologuard in the clinical trial. He added that a precursor to Cologuard had at one time been on an ACS-recommended list of colorectal cancer screening options, but the test is no longer available.

"Cologuard has more robust data than the older stool DNA test and better performance," Wender said, "so a good argument for including the test in guidelines can be made."

CMS Coverage

Cologuard is the first product to be reviewed through a joint FDA-CMS pilot program for parallel review,(www.fda.gov) under which the agencies concurrently review certain premarket medical devices to reduce the time between FDA approval and Medicare coverage.

"Parallel review allows the last part of the FDA process to run at the same time as the CMS process, cutting as many as six months from the time of study initiation to coverage," said Nancy Stade, CDRH's deputy director for policy, in the news release.

CMS proposes to cover the Cologuard test once every three years for asymptomatic individuals ages 50 to 85 who are at average risk of developing colorectal cancer.

"This new process (of parallel review) is a good step in developing a more efficient and streamlined approach to test approval," Wender said. "I applaud the FDA and CMS for developing this innovative process to accelerate the availability of the test.

"I think it is fair to say that having both agencies join in approving the test and paying for the test does constitute additional endorsement of the test."

The Future for Cologuard

For Cologuard to become widely used, it will need to be added to the USPSTF and other major colorectal cancer screening guidelines, Wender said. Otherwise, the test may not be covered by some commercial insurers.

As to Cologuard's limitations, Wender said that although CMS has decided to pay for the test every three years, the ideal testing interval has not yet been determined. Furthermore, at a cost of $500 (the preliminary payment amount established by CMS), the test is likely to be cost-effective but its relative cost-effectiveness compared to other screening options is unclear. Finally, the acceptability of the test to clinicians and patients also is not fully known.

Wender said it's important for physicians to remember that there are already two widely used screening options: colonoscopy every 10 years or FIT every year. He added that high-sensitivity guaiac FOBT and CT colonoscopy are additional options to consider. The variety of options should help the ACS reach its "80% by 2018"(nccrt.org) initiative's goal to have 80 percent of adults ages 50 and older screened for colorectal cancer by 2018.

"In short, we already have both more and less invasive, more and less costly options to screen everyone for colorectal cancer," said Wender. "We can achieve the 80 percent goal using available tests. But it is conceivable that having Cologuard available and approved may place the 80 percent goal more within our reach."

Tomado de: http://www.aafp.org/

Referencias:: American Cancer Society: How to Increase Colorectal Cancer Screening Rates in Practice: A Primary Care Clinician's Evidence-Based Toolbox and Guide 2008(www.cancer.org)