Medical Bulletin 28/ September/ 2024 - Video

The dynamics of blood nutrient and lipid levels after consuming a high-fat meal are crucial indicators of both current and future cardiovascular health. A promising, noninvasive approach to measure these circulating substances is a noncontact optical imaging technique called “spatial frequency domain imaging” (SFDI), which quantifies tissue properties and hemodynamics.

A recent study from Boston University, Harvard Medical School, and Brigham and Women's Hospital investigated how meal composition affects skin tissue properties shortly after eating. As reported in Biophotonics Discovery (BIOS), the research team focused on the peripheral tissue of the hand to understand the immediate impacts of low-fat and high-fat meals.

Using spatial frequency domain imaging, the researchers monitored 15 subjects who consumed both types of meals on separate days. The team imaged the back of each subject's hand hourly for five hours post-meal, analyzing three specific wavelengths to evaluate hemoglobin, water, and lipid concentrations.

The results revealed significant differences in tissue responses. The high-fat meal led to an increase in tissue oxygen saturation, while the low-fat meal caused a decrease, suggesting that dietary fat can affect not just overall health but also immediate physiological responses. The peak changes occurred three hours after eating, coinciding with spikes in triglyceride levels.

Alongside imaging, researchers tracked blood pressure and heart rate, and also performed blood draws to measure triglycerides, cholesterol, and glucose levels. The results indicated that the optical absorption changes at specific wavelengths accurately correspond to variations in lipid concentrations.

Building on these insights, the team then trained a machine learning model using spatial frequency domain imaging data to predict triglyceride levels, achieving an accuracy within 40 mg/dL. This precision could pave the way for noninvasive monitoring of cardiovascular health.

Senior author Darren Roblyer, professor of biomedical engineering at Boston University, remarks, “The research suggests that spatial frequency domain imaging could serve as a promising alternative, allowing for easier monitoring of how meals affect cardiovascular health.” He adds, “Overall, these findings highlight the intricate relationship between diet, body response, and cardiovascular risk, suggesting a need for further exploration of non-invasive assessment methods.”

Reference: Anahita Pilvar, Jorge Plutzky, Darren Roblyer, "Enhanced peripheral tissue oxygenation and hemoglobin concentration after a high-fat meal measured with spatial frequency domain imaging," Biophoton. Discovery 1(2) 025004 (12 September 2024) https://doi.org/10.1117/1.BIOS.1.2.025004

In a new study from the University of South Australia, researchers say that parents and doctors should be mindful of how they talk to and treat children experiencing pain – no matter how big or small the injury – knowing that these foundational experiences can be carried forward into adulthood.

Drawing from diverse research across developmental psychology, child mental health, and pain sciences, researchers say that it may be important to validate children’s pain by demonstrating that their pain-related experiences, emotions, or behaviours are acceptable, understood, and legitimate. By validating a child’s pain, the child feels heard and believed, which reinforces their trust and connection with their parent, or with a treating doctor.

“When a parent or doctor validates a child’s experiences in a way that matches their expressed vulnerability, it helps the child to feel accepted, builds connection and trust, and may help the child to develop critical skills in regulating their emotions,” UniSA researcher Dr Sarah Wallwork says.

“However, if these cues are missed, or the doctor questions the validity of their pain, this can have negative consequences for the child. Not only can it affect the clinician-patient relationship and trust but it can also impact future attendance at appointments and adherence to a pain management plan.

“By validating children’s experiences of pain, they are likely to hold fewer negatively biased memories of pain and be in better position to seek help in the future, when they need it.”

Dr Wallwork says that setting children up for success should cover all aspects of life, including pain management.

“Our research highlights an underemphasised element of child and youth pain treatment, especially for children in minoritised groups, who are systematically undertreated for pain,” Dr Wallwork says. “People with chronic pain often report that their pain-related experiences are met with disbelief or dismissal. This can have significant consequences, including poor mental health and reduced quality of life.

“Given the significant burden of chronic pain, and the clear intersection with the rising child mental health crisis, it’s important that we better manage pain earlier on, rather than waiting until it is too late.” Dr Wallwork says this review provides a building block for future empirical research.

Reference: Wallwork, Sarah B.a,*; Shenk, Chadb,c; McMurtry, C. Meghand; Hood, Anna M.e; Pavlova, Mariaf; Olson, Anneke E.b; Moseley, G. Lorimera; Noel, Melanieg. “I hear you”. Validation in the context of children's pain as an untapped opportunity to prevent chronic pain. PAIN ():10.1097/j.pain.0000000000003350, July 30, 2024. | DOI: 10.1097/j.pain.0000000000003350

The research, published in Human Reproduction, is the largest to investigate the link between autoimmune conditions and premature ovarian insufficiency and has followed nearly 20,000 women.

The researchers say their findings significantly strengthen the hypothesis that autoimmune processes play a “pivotal role” in the onset of premature ovarian insufficiency.

Dr Susanna Savukoski, a gynaecology and obstetrics doctor at Oulu University Hospital and University of Oulu, Finland, led the study. She said: “Estimates of the prevalence of premature ovarian insufficiency of autoimmune origin have ranged from 4% to 50%. Our study has found that autoimmune diseases were two-to-three-fold more common in women diagnosed with premature ovarian insufficiency at the time they were diagnosed, and incidence of these diseases was two-to-three-fold higher during the first years after being diagnosed with premature ovarian insufficiency, compared to a control group of similarly aged women from the general population. The incidence was higher than in the control group even more than a decade after being diagnosed with premature ovarian insufficiency.”

Dr Savukoski and her colleagues analysed health data from Finland’s comprehensive registries. From the medicine reimbursement registry maintained by the Social Insurance Institution of Finland, they identified 3972 women who had been granted the right to full reimbursement for hormone replacement therapy (HRT) because of premature ovarian insufficiency diagnosis under the age of 40 years, between the years 1988 and 2017. Each woman with premature ovarian insufficiency was matched with four women of similar ages, forming a control group of 15708 women. In both groups of women, they analysed data on severe autoimmune conditions – diseases that were diagnosed and treated in specialist health centres – between 1970 and 2017.

They found that among women who were diagnosed with premature ovarian insufficiency, 223 women (5.6%) had been diagnosed with at least one autoimmune disorder before the date when reimbursement for hormone replacement therapy because of premature ovarian insufficiency was granted, and 503 women (12.7%) were diagnosed with at least one autoimmune disorder after the date of hormone replacement therapy during the follow-up period.

Women were 2.6 times more likely to have an autoimmune disorder before a premature ovarian insufficiency diagnosis when compared to the control group. Among women with premature ovarian insufficiency, the risk of autoimmune conditions ranged from nearly double for over-active thyroid glands, to nearly 26 times for polyglandular autoimmune diseases – rare diseases of the endocrine system.

Women without existing autoimmune diseases at the time they were diagnosed with premature ovarian insufficiency were nearly three times as likely to be diagnosed with an autoimmune disease in the following three years, with the risk decreasing but still significantly higher than in the control group during the follow-up period of at least 12 years.

Reference: S M Savukoski, H Silvén, P Pesonen, E Pukkala, M Gissler, E Suvanto, M -M Ollila, M Niinimäki, Excess of severe autoimmune diseases in women with premature ovarian insufficiency: a population-based study, Human Reproduction, 2024;, deae213, https://doi.org/10.1093/humrep/deae213

Adults with hemophilia B saw their number of bleeding episodes drop by an average of 71 percent after a single infusion of gene therapy, according to the results of an international Phase III clinical trial published in the New England Journal of Medicine by researchers from the University of Pennsylvania Perelman School of Medicine and a multicenter group of investigators.

“What we saw from patients in this study was that within a few days of receiving the gene therapy infusion, it took root, and their bodies started making factor IX for the first time in their lives,” said study investigator and lead author Adam Cuker, MD, MS, section chief for Hematology, and clinical director of the Penn Blood Disorders Center and the Penn Comprehensive Hemophilia Program. “We always want to be careful about using the word ‘cure’ especially until we have longer follow-up data, but for many of these patients, it’s been life changing.”

Based on the results of this study, the FDA approved the gene therapy (fidanacogene elaparvovec) in April 2024. Cuker was the site lead for the clinical trial at Penn Medicine, which was one of the top-enrolling sites for the study. It represents the second form of gene therapy approved to treat hemophilia B. The first such therapy (etranacogene dezaparvovec-drlb) was approved in November 2022.

In the current study, the most common adverse effect was related to an immune system attack on liver cells that were targeted by the gene therapy, which can render the gene therapy ineffective, if not quickly treated. In the study, affected patients were treated with steroids to limit this immune reaction. Patients in the study will continue to be followed for at least five years to monitor potential long-term side effects.

The new gene therapy only requires a single dose in contrast to the standard therapy and most patients in the study did not need to resume prophylactic factor IX treatments.

“We hear from people born with hemophilia that—even if their disease is well-managed—there’s this burden that’s always in the back of their mind. The frequent infusions, the cost of treatment, the need to plan for infusions when traveling, what happens if they do experience a bleed, and so on, is always there,” Cuker said. “Now that we have patients who were treated on this study and are essentially cured of their hemophilia, they’re telling us about realizing a new, ‘hemophilia-free state of mind.’ As a physician, it’s amazing to see my patients so happy with their new reality.”

Reference: Cuker, A., Kavakli, K., Frenzel, L., Wang, J.-D., Astermark, J., Cerqueira, M. H., Iorio, A., Katsarou-Fasouli, O., Klamroth, R., Shapiro, A. D., Hermans, C., Ishiguro, A., Leavitt, A. D., Oldenburg, J. B., Ozelo, M. C., Teitel, J., Biondo, F., Fang, A., Fuiman, J., McKay, J., Sun, P., Rasko, J. E. J., & Rupon, J. (2024). Gene therapy with fidanacogene elaparvovec in adults with hemophilia B. New England Journal of Medicine, 391(12), 1108-1118. https://doi.org/10.1056/NEJMoa2302982