A New Blood Test for Identifying IBS and the Importance of Providing Clear Answers for Patients

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Narrator: You are listening to ReachMD. Welcome to this Medical Industry Feature, sponsored by Quest Diagnostics. The following program is intended for healthcare professionals only. Your host is Mario Nacinovich.

Host: On today’s program, we will be discussing IBS and the importance of testing to help your patients understand their gut problems.

I’m your host Mario Nacinovich and joining me today is Dr. Christine Frissora, Gastroenterologist and leading IBS expert.

Dr. Frissora, welcome to the program. We’re looking forward to hearing your perspectives today.

Guest: Thank you so much Mario. I’m glad to be here to discuss something that affects millions of Americans and causes a lot of suffering in my patients.

Host: Dr. Frissora, let’s start with some foundational updates on irritable bowel syndrome. How do we define the disease, who does it affect, and what do we think may cause it?

Novel Oral Tx Dramatically Reduces Menopausal Flushing

https://goo.gl/nXCN2T

A neurokinin 3 receptor (NK3R) antagonist was effective at improving vasomotor symptoms without the need for estrogen exposure, both in the short and long-term, researchers reported.

The oral NK3R antagonist MLE4901 was able to reduce the frequency of hot flashes by 72% by day 3 of treatment versus baseline symptoms (95% CI -81.3% to -63.5%) and a 51% improvement in frequency with the oral treatment compared with those on placebo, according to Julia K. Prague, MBBS, of Imperial College London, and colleagues.

Without tapering off, this effect was maintained throughout the 4-week study, they wrote in Menopause: The Journal of The North American Menopause Society.

"We conducted this study because menopausal flushing is a major problem, which affects the lives of millions of women worldwide and current treatments have side effects or are not effective," co-author Waljit S Dhillo, MBBS, PhD, also of Imperial College London, explained to MedPage Today. "We expected the neurokinin 3 receptor antagonist to reduce hot flushes based on previous data in animals, which suggested this approach should work to relieve menopausal flushing. However we were surprised at how effective the drug worked -- almost a miracle drug for this condition."

Neurokinin B/NK3R signaling is critical in menopausal flushing, and may be attenuated by administration of an oral NK3R antagonist, but without the addition of estrogen, according to the authors.

Low-Dose Combo Pill Successfully Takes Down High BP

https://goo.gl/wpKRrH

Patients with untreated or uncontrolled hypertension reached blood pressure goals after treatment with a low-dose "triple pill," researchers reported here.

In a study conducted in Sri Lanka and among 647 patients with data at 6 months, the triple-pill was associated with greater achievement of blood pressure target levels compared with usual care (70% versus 55%, RR 1.23, [95% CI 1.09, 1.39, P=0.0007), according to Ruth Webster, PhD, MBBS, of the George Institute for Global Health at the University of New South Wales in Sydney, and colleagues.

The triple pill was a fixed-dose combination of telmisartan (20 mg), amlodipine (2.5 mg), and chlorthalidone (12.5 mg). An option for a a double dose version at or after 6 weeks was allowed.

The maximum difference in treatment arms was observed at 6 weeks (68% versus 44%, RR 1.53, 95% CI 1.33, 1.76, the authors reported in a presentation at the American College of Cardiology annual meeting.

"Based on our findings, we conclude that this new method of using blood pressure-lowering drugs was more effective and just as safe as current approaches," Webster said.


Everyone with the sickle cell gene mutation descended from the same ancestor 7,300 years ago

Just for context, the first half dozen expeditions into pre-revolutionary war Michigan resulted in a high death rate from malaria.

https://goo.gl/5HsY9L

A one-time gene mutation in a West African human millennia ago gave them immunity to malaria and doomed some of their descendants to sickle cell anaemia, according to new research.

Today, about 300,000 children are born with sickle cell anaemia every year, with that number expected to rise to 400,000 in the next 30 years. The majority of these cases occur in Nigeria, the Democratic Republic of Congo, and India, and many of these babies are likely to die from the disease in which their red blood cells break apart, leaving their bodies starved of oxygen. It is caused by two copies of a gene mutation in their DNA. One copy is harmless; two copies can be deadly. Millions of people worldwide, frequently those with African heritage, are carriers of this mutant gene, but there are large gaps in our knowledge of the disease and its characteristic mutations.

Sickle cell anaemia contributes the equivalent of 5% of deaths of under-five-year-old children on the African continent, according to the W.H.O, more than 9% of such deaths in west Africa, and up to 16% of under-five deaths in individual west African countries.

The new research, published in scientific journal Cell, has found that this disease began with a single ancestor who developed the mutation to fend of malaria.

Translocation of a gut pathobiont drives autoimmunity in mice and humans

A bug from the gut can get into body organs and trigger autoimmune reactions....

The composition of the commensal microbiota is known to influence autoimmune disease development and persistence. Manfredo Vieira et al. identified a gut microbe, Enterococcus gallinarum, that translocates from the gut into the organs of mice with a genetic predisposition to lupus-like autoimmunity (see the Perspective by Citi). Molecular signatures of gut barrier disintegration and pathogenic T helper cells were evident in the gut, liver, and lymphoid organs during colonization with the pathobiont. The ensuing pathology could be reversed by vancomycin treatment and by vaccination against E. gallinarum. The same bug was also found in liver biopsies of autoimmune patients, but not in healthy controls.


Concentrating on the causes of insulin resistance

After we eat, our blood sugar levels increase. To counteract this, the pancreas releases a hormone called insulin. Part of insulin’s effect is to promote the uptake of sugar from the blood into muscle and fat tissue for storage. Under certain conditions, such as obesity, this process can become defective, leading to a condition known as insulin resistance. This condition makes a number of human diseases more likely to develop, including type 2 diabetes. Working out how insulin resistance develops could therefore unveil new treatment strategies for these diseases.

Mitochondria — structures that produce most of a cell’s energy supply — appear to play a role in the development of insulin resistance. Mitochondria convert nutrients such as fats and sugars into molecules called ATP that fuel the many processes required for life. However, ATP production can also generate potentially harmful intermediates often referred to as ‘reactive oxygen species’ or ‘oxidants’. Previous studies have suggested that an increase in the amount of oxidants produced in mitochondria can cause insulin resistance.

Fazakerley et al. therefore set out to identify the reason for increased oxidants in mitochondria, and did so by analysing the levels of proteins and oxidants found in cells grown in the laboratory, and mouse and human tissue samples. This led them to find that concentrations of a molecule called coenzyme Q (CoQ), an essential component of mitochondria that helps to produce ATP, were lower in mitochondria from insulin-resistant fat and muscle tissue. Further experiments suggested a link between the lower levels of CoQ and the higher levels of oxidants in the mitochondria. Replenishing the mitochondria of the lab-grown cells and insulin-resistant mice with CoQ restored ‘normal’ oxidant levels and prevented the development of insulin resistance.

Strategies that aim to increase mitochondria CoQ levels may therefore prevent or reverse insulin resistance. Although CoQ supplements are readily available, swallowing CoQ does not efficiently deliver CoQ to mitochondria in humans, so alternative treatment methods must be found. It is also of interest that statins, common drugs taken by millions of people around the world to lower cholesterol, also lower CoQ and have been reported to increase the risk of developing type 2 diabetes. Further research is therefore needed to investigate whether CoQ might provide the link between statins and type 2 diabetes.


Strict Eating Schedule Can Lower Huntington’s Protein: Mouse Study

This is an astounding mechanism....

New research from the University of British Columbia suggests that following a strict eating schedule can help clear away the protein responsible for Huntington disease in mice.

Huntington disease (HD) is an inherited, progressive disorder that causes involuntary movements and psychiatric problems. Symptoms appear in adulthood and worsen over time. Children born to a parent with HD have a one in two chance of inheriting the disease, which is caused by a buildup of mutant huntingtin protein (mHTT).

In research published today, scientists stimulated autophagy–a process in which the cell cleans out debris and recycles cellular material such as proteins–by restricting access to food in mice with HD to a six-hour window each day. This led to significantly lower levels of mHTT in the brain.

“We know that specific aspects of autophagy don’t work properly in patients with Huntington disease,” said study lead author Dagmar Ehrnhoefer, who conducted the study while she was a researcher with the UBC Centre for Molecular Medicine and Therapeutics. “Our findings suggest that, at least in mice, when you fast, or eat at certain very regulated times without snacking in between meals, your body starts to increase an alternative, still functional, autophagy mechanism, which could help lower levels of the mutant huntingtin protein in the brain.”


Folic Acid in Utero Tied to Food Allergy Risk

A similar problem with un-metabolized folic acid occurs in adults as well, producing higher body histamine levels...

Newborns with high levels of unmetabolized folic acid had a higher risk for food allergy later in childhood than newborns with lower circulating folic acid levels -- suggesting that increased exposure to synthetic folic acid in utero could be a risk factor for food allergy.

In a nested case-control study performed using data from the Boston Birth Cohort, mean folate levels at birth were found to be lower among children who went on to develop food allergies, while mean levels of unmetabolized folic acid were higher.

The research was presented here at the joint meeting of the American Academy of Allergy, Asthma & Infectious Disease (AAAAI) and the World Allergy Organization (WAO).

"Food allergy prevalence seems to be increasing, and it has been hypothesized that increased [in utero] folic acid exposure may be a central contributor to this," said study co-author Corinne Keet, MD, PhD, of Johns Hopkins Hospital in Baltimore.

In a press conference at the meeting Keet said early research suggests that unmetabolized folic acid could have a negative impact on health. In the early 1990s folic acid was found to be protective of neural tube birth defects, and in 1998 the U.S. mandated the fortification of flour and other grain products with folic acid. Supplementation with 400 micrograms of folic acid is also recommended for women in their childbearing years.

"When the synthetic form of folate is metabolized, only a certain amount is able to be processed through the normal pathways, and the excess circulates as unmetabolized folic acid," Keet said.


New Way to Classify Adult-Onset Diabetes, Explained

A novel classification system for adult-onset diabetes, eschewing the usual type 1 and type 2 designation in favor of five subgroups, distinguishes unique disease progression and risk for related complications, researchers reported.

The five unique subgroups based on severity and underlying disease mechanism analysis -- reported by Emma Ahlqvist, PhD, of Lund University in Sweden, and colleagues in the Lancet Diabetes & Endocrinology -- were:

  • Cluster 1: Severe autoimmune diabetes (SAID)
  • Cluster 2: Severe insulin-deficient diabetes (SIDD)
  • Cluster 3: Severe insulin-resistant diabetes (SIRD)
  • Cluster 4: Mild obesity-related diabetes (MOD)
  • Cluster 5: Mild age-related diabetes (MARD)

The first cluster -- defined as severe autoimmune diabetes -- was the least common, with only 6.4% of the cohort fitting this type. Clinical characteristics included early-onset of the disease and being GADA positive, along with a lower BMI, poor metabolic control, and insulin deficiency. This group had the largest proportion of patients prescribed insulin (42%), as well as the shortest time to insulin use (HR 26.87 versus cluster 5, 95% CI 21.17-34.11).

Cluster 2 was mainly defined as severely insulin-deficient as well as GADA negative. Other clinical characteristics were similar to cluster 1, although this group had the highest proportion of patients on metformin.

The third cluster, accounting for 15.3% of the cohort, was marked by both a high degrees of insulin resistance -- specifically a high HOMA2-IR index -- paired with a high BMI. This group had relatively low use of metformin, despite the authors noting that this group would likely see the most benefit from such treatment.

Around one-fifth of patients belonged to cluster 4, defined by a presence of obesity without insulin resistance.

The fifth and most common cluster, which comprised nearly 40% of patients with adult-onset diabetes, was marked by an older age of diabetes onset, without as poor a metabolic profile as other clusters.


Pedestrian Deaths in Road Accidents Hit 25-Year High


Nearly 6,000 pedestrians were killed in the U.S. in 2017, according to a new study, and some experts have linked the accidents to distractions such as smartphones and marijuana.

Richard Retting, the director of safety for Sam Schwartz Consulting and author of the report, said: “People outside cars are dying at levels we haven’t seen in 25 years.” It’s not certain why so many more people are dying outside cars than a few years ago, but the report noted that, in the seven states that legalized pot for recreational purposes, as well as the District of Columbia, pedestrian deaths spiked 16.4 percent in the first half of 2017, while deaths fell elsewhere.

“We’re not making a definitive link here and saying this is an ‘aha’ moment, but it’s a source of concern and we think greater attention needs to be paid to this issue,” Retting said. Rebecca Lindland, a Kelley Blue Book auto analyst, said pedestrians distracted by smartphones could be to blame.

“At some point in time people both behind the wheel and walking in the street have to take responsibility for their behavior and put down the phone,” she said.