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Research Briefs March 2018

Omalizumab Helps Relieve Food Allergies

More than 80% of children who were given omalizumab (Xolair, Genentech/Novartis) with oral immunotherapy (OIT) for 36 weeks could safely consume portions of at least two foods they were allergic to, according to findings from a phase 2 study funded by the National Institute of Allergy and Infectious Diseases (NIAID). Omalizumab, an injectable monoclonal antibody approved for moderate-to-severe allergic asthma, blocks the activity of immunoglobulin E.

Researchers from Stanford University enrolled 48 children 4 to 15 years of age with confirmed allergies to multiple foods, including milk, eggs, wheat, soy, sesame seeds, peanuts, and tree nuts. The children received omalizumab or placebo injections for the first 16 weeks. At week 8, all participants began eating small, gradually increasing amounts of an allergenic food. They continued OIT until week 36, when they underwent an oral food challenge.

Of the 36 children who received omalizumab, 30 were able to eat at least 2 g of two or more of allergenic foods compared with only four of the 12 children (33%) who received placebo. Children who received omalizumab also had fewer adverse events from OIT.

Source: NIAID, December 2017

Uncovering Clues to Explain Cisplatin’s Ototoxicity

Cisplatin and other platinum-based drugs are prescribed for 10% to 20% of cancer patients. The drugs cause permanent hearing loss in as many as 80% of adult patients and at least half of children. Why is cisplatin so toxic to the inner ear?

Researchers from the National Institute on Deafness and Other Communication Disorders (NIDCD) may have found the answer: The inner ear readily takes up cisplatin, they say, but has very little ability to remove the drug. In most areas of the body, cisplatin is eliminated within days or weeks after treatment; in the inner ear, it remains for much longer.

Using a mouse model, the researchers found cisplatin remained in the inner ear much longer than in most other body tissues and built up with each treatment. They also studied inner ear tissue donated by deceased patients who had been treated with cisplatin and found cisplatin remained in the inner ear for many months or even years after treatment. They also examined inner ear tissue from one child and found even greater cisplatin buildup than that seen in adults.

The highest buildup of cisplatin was in the stria vascularis, which helps maintain the positive electrical charge in inner ear fluid that certain cells need to detect sound, the researchers say. They believe that accumulation contributed to the hearing loss. “If we can prevent cisplatin from entering the stria vascularis in the inner ear during treatment,” says Lisa Cunningham, PhD, lead investigator, “we may be able to protect cancer patients from developing cisplatin-induced hearing loss.”

Source: NIDCD, December 2017

Self-Reported Cognitive Impairment Is Rising

More people are reporting cognitive impairment, according to researchers from the Centers for Disease Control and Prevention. Overall, the rate of self-reported cognitive impairment rose from 5.7% in 1997 to 6.7% in 2015. Among non-Hispanic white respondents, the rate went from 5.2% to 6.1%. The researchers found no significant trends in cognitive impairment among Native American, Hispanic, non-Hispanic African-American, or Asian respondents.

Respondents to the National Health Survey were asked whether any family member was “limited in any way because of difficulty remembering or because of experiencing periods of confusion.” The rate of cognitive impairment increased with age in all five racial/ethnic groups. The rate was lowest among non-Hispanic Caucasian respondents until the 1943–1947 birth cohort. The data are “interesting,” the researchers say, because other recent studies that used data from cognitive tests and clinical assessments found a declining trend in dementia in the U.S. They note that direct comparison among studies is inappropriate, however, because of different study designs. Their own findings “might suggest that awareness of cognitive impairment has improved in the United States, especially in recent years,” in part due to heightened public attention to Alzheimer’s disease.

More public education may be needed to promote awareness, the researchers say, especially among minority groups. Minorities had lower rates of self-reporting, perhaps because of different cultural beliefs about disease and aging, or because they are less likely to seek treatment for depression, which can contribute to cognitive decline.

Source: Preventing Chronic Disease, January 2018

Linking Metabolic Health, Psychiatric Disease, and Oxytocin Levels

African-American men with diabetes may be at risk for significantly low levels of oxytocin (OT), according to a study of 92 veterans by researchers from the Jesse Brown VA Medical Center. Research has recently been revealing oxytocin’s role in energy homeostasis; OT derangements have also been implicated in a variety of disease states, including schizophrenia, autism, depression, and attention-deficit/hyperactivity disorder.

The researchers note that the study participants represent a “unique population” of African-American male veterans for whom no data on OT levels exist in the literature. The population has a disproportionately high rate of obesity and dysglycemia, as well as high rates of comorbid psychiatric disease.

In the study, urinary OT was higher in men with lower weight, body mass index (BMI), and hemoglobin A1c and better renal function. Men with the highest levels of OT were about 80% less likely to have type-2 diabetes. The researchers say several studies have appeared to show that intranasal OT may reduce reward-driven food intake, and that OT administration may result in weight reduction.

Men with high oxytocin levels were four times more likely to be using psychiatric medications. Although there was no difference in psychiatric conditions based on OT levels, the use of psychiatric medications remained significant after adjustment for BMI. The influence of psychiatric medications on oxytocinergic systems is not well understood, the researchers say. However, they add that medication-related improved psychological health outcome might result in OT changes.

Interestingly, men with high oxytocin levels were also four times more likely to be smokers. The researchers note that chronic administration of nicotine appears to upregulate OT receptor binding in regions of the brain involved in stress and emotion regulation, and these neuroadaptations likely influence nicotine-seeking behavior. Intranasal OT is being investigated for smoking cessation.

Source: PLoS ONE, January 2018

When Guilt and Depression Hinder PTSD Treatment

Guilt and depression put an added burden on a patient with severe post-traumatic stress disorder (PTSD)—enough to make a critical difference in response to treatment, say researchers from the University of Melbourne and University of New South Wales. The triad of conditions interferes with an individual’s capacity to fully engage in trauma-focused treatment or successfully process trauma memories, they conclude.

The researchers analyzed patterns and predictors of treatment response trajectories for 2,686 Australian veterans with PTSD. The veterans completed the PTSD Checklist at intake, discharge, and at three and nine months follow-up. The researchers found five distinct classes: Those veterans with the most severe PTSD at intake separated into a relatively large class (32.5%) with small change, and a small class (3.0%) with a large change. A third group included those with slightly less severe PTSD (49.9%) with large change effects and another group (7.9%) with extremely large treatment effects. The fifth class (6.7%) with least severe symptoms at intake also showed a large treatment effect.

Of the predictor variables the researchers used, only depression and guilt predicted differences in response trajectory.

When a patient has both PTSD and depression, PTSD treatment guidelines recommend that the two conditions be treated concurrently unless the severity of the depression precludes effective engagement in trauma-focused therapy, the researchers note. But when guilt is part of the mix, it is likely to be “integrally linked” to the traumatic event—meaning it may not be possible to address the guilt without addressing the trauma.

Their findings highlight the importance of assessing guilt and depression before deciding on treatment, the researchers say. For patients with severe symptoms, they suggest, it may be prudent to use a trauma-focused approach that directly targets the guilt-related cognitions or depression to improve the level of effective and cognitive flexibility needed for the PTSD treatment to be effective.

Source: Psychological Medicine, January 2018

Albumin/Globulin Levels Can Predict Cancer Prognosis

Does the albumin/globulin ratio (AGR) predict prognosis in digestive system cancers? No convincing conclusions had been made, say researchers from Nan Chang University, so they conducted a meta-analysis of 15 studies involving nearly 10,000 patients to find out. The results indicate that a low pretreatment AGR was significantly related to worse survival outcomes for patients with colorectal and other cancers of the digestive system.

Of the analyzed studies, 13 explored the association of AGR with overall survival and found a low AGR nearly doubled the risk of death. When the researchers adjusted for cancer type, region, sample size, treatment method, and other variables, a low AGR remained a predictor for worse overall survival in colorectal, esophageal, and gastric cancer, respectively. Two studies explored the association of a low AGR with cancer-specific survival; again, a low AGR was significantly related to worse outcome.

The researchers say effects of nutrition and inflammation may underlie the prognostic value of the AGR. They refer to the “mutual promotion effect” between cancer progression and inflammation, and to the fact that cancer patients are vulnerable to cachexia, which also contributes to tumor growth. Moreover, serum albumin not only reflects the body’s nutritional status but, according to recent research, the inflammatory status as well. The serum globulin level is closely associated with immune and inflammatory status and is easily affected by dehydration and fluid retention, common to cancer patients.

Thus, the AGR, which takes both levels into account concurrently, may mirror nutritional and inflammatory indices more precisely, the researchers say, and could be a helpful biomarker.

Source: PLoS ONE, January 2018