Tag: 21/5/24

Categories : Environmental Effects Respiratory DiseasesTags :

Extreme Heat Linked to Children’s Asthma Hospital Visits

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Credit: Pixabay CC0

For children seeking care at a California urban paediatric health centre, extreme heat events were associated with increased asthma hospital visits, according to research published at the ATS 2024 International Conference.

“We found that both daily high heat events and extreme temperatures that lasted several days increased the risk of asthma hospital visits,” said corresponding author Morgan Ye, MPH, research data analyst, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco School of Medicine. “Understanding the impacts of climate-sensitive events such as extreme heat on a vulnerable population is the key to reducing the burden of disease due to climate change.”

Ms Ye and colleagues looked at 2017-2020 electronic health records from the UCSF Benioff Children’s Hospital Oakland, which included data on asthma hospital visits by patients of the hospital, some of whom are from Benioff Oakland’s Federally Qualified Health Center, and demographics including patients’ zip codes. They used data from the PRISM Climate Group of Oregon State University to determine the timing of daily maximum (daytime heat waves) and minimum (nighttime heat waves) for each zip code. The researchers restricted their analyses to the region’s warm season (June to September). To evaluate the potential range of effects of different heat wave measurements, they used 18 different heat wave definitions, including the 99th, 97.5th and 95th percentile of the total distribution of the study period for one, two or three days.

They designed the study in a way that allowed them to determine the association between each heat wave definition and a hospital visit. They repeated the analysis for Bay Area and Central California zip codes.

The team discovered that daytime heat waves were significantly associated with 19% higher odds of children’s asthma hospital visits, and longer duration of heat waves doubled the odds of hospital visits. They did not observe any associations for night-time heat waves.

According to Ye, “We continue to see global temperatures rise due to human-generated climate change, and we can expect a rise in health-related issues as we observe longer, more frequent and severe heat waves. Our research suggests that higher temperatures and increased duration of these high heat days are associated with increased risk of hospital visits due to asthma. Children and families with lower adaptation capacity will experience most of the burden. Therefore, it is important to obtain a better understanding of these heat-associated health risks and susceptible populations for future surveillance and targeted interventions.”

The authors note that past research has suggested positive associations between extreme heat and asthma, but findings regarding hospitalisations and emergency room visits have been conflicting. Additionally, many other studies have focused on respiratory hospitalizations and not hospitalizations for asthma, specifically, and have not included or had a focus on children. This study is also unique because it investigated the effect of daily high temperatures but also the effects of persistent extreme temperatures.

The San Francisco Bay Area and California overall are unique areas of interest because the state is considered a coastal region with less prevalence of cooling units, such as air conditioners. While temperatures may not reach the extremes experienced in other parts of the country, this study demonstrates that even milder extreme heat temperatures may significantly impact health. These effects are more pronounced in climate-susceptible populations, including children and those who are medically vulnerable, such as those served by the urban paediatric health centre in this study. The authors hope these study results will lead to more equitable health outcomes and reduce racial/ethnic disparities observed in climate-sensitive events.

“These results can be used to inform targeted actions and resources for vulnerable children and alleviate health-related stress during heat waves,” they conclude.

Source: American Thoracic Society

Categories : Diseases, Syndromes and ConditionsTags :

First Test of Drug in a Patient with Rare Blood Clotting Disorder is a Success

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Source: Wikimedia CC0

A team led by investigators from Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system, used a new drug to save the life of a patient with immune thrombotic thrombocytopenic purpura (iTTP), a rare disorder characterised by uncontrolled clotting throughout the small blood vessels. The group describes the first clinical use of the drug for iTTP in the New England Journal of Medicine.

“The drug is a genetically engineered version of the missing enzyme in iTTP, and we showed that it was able to reverse the disease process in a patient with an extremely severe form of this condition,” said lead author Pavan K. Bendapudi, MD, an investigator in the Division of Hematology and Blood Transfusion Service at Massachusetts General Hospital and an assistant professor of Medicine at Harvard Medical School.

iTTP results from an autoimmune attack against an enzyme called ADAMTS13 that is responsible for cleaving a large protein involved in blood clotting. The current mainstay of therapy for this life-threatening blood disorder is plasma exchange, which removes the harmful autoantibodies and provides extra ADAMTS13. Plasma exchange induces a clinical response in most patients but can restore at best only about half of normal ADAMTS13 activity. By contrast, a recombinant form of human ADAMTS13 (rADAMTS13) offers the possibility of greatly increased ADAMTS13 delivery.

rADAMTS13 was recently approved for patients with congenital thrombotic thrombocytopenic purpura, which occurs in patients born with complete loss of the ADAMTS13 gene. It’s questionable whether rADAMTS13 could be effective in iTTP given the presence of inhibitory anti-ADAMTS13 autoantibodies, but Bendapudi and his colleagues received permission from the US Food and Drug Administration to utilize rADAMTS13 donated from the manufacturer under a compassionate use protocol in a dying patient with treatment-resistant iTTP.

“We found that rADAMTS13 rapidly reversed this patient’s disease process despite the current dogma that inhibitory autoantibodies against ADAMTS13 would render the drug useless in this condition,” said Bendapudi. “We were the first physicians to use rADAMTS13 to treat iTTP in the United States, and in this case it helped to save the life of a young mother.”

Bendapudi noted that the infused rADAMTS13 overwhelmed the inhibitory autoantibodies in the patient and reversed the thrombotic effects of iTTP. This impact was observed almost immediately upon administration of rADAMTS13, after daily plasma exchange had failed to induce remission.

“I think rADAMTS13 has the potential to replace the current standard of care in acute iTTP. We will need larger, well-designed trials to evaluate this possibility,” said Bendapudi.

A phase 2b randomized clinical trial of rADAMTS13 in iTTP was recently initiated.

Source: Massachusetts General Hospital

Categories : COVID OphthalmologyTags :

SARS-CoV-2 can Cross the Blood–Retinal Barrier, Infecting the Eyes

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Photoreceptor cells in the retina. Credit: Scientific Animations

The blood-retinal barrier is designed to protect vision from infections by preventing microbial pathogens from reaching the retina where they could trigger an inflammatory response with potential vision loss. But researchers at the University of Missouri School of Medicine have discovered that SARS-CoV-2 can breach this protective retinal barrier with potential long-term consequences in the eye. Their findings are reported in PLOS Pathogens.

Pawan Kumar Singh, PhD, an assistant professor of ophthalmology, leads a team researching new ways to prevent and treat ocular infectious diseases. Using a humanised ACE2 mice model, the team found that SARS-CoV-2, can infect the inside of the eyes even when the virus doesn’t enter the body through the surface of the eyes. Instead, they found that when viruses enter the body through inhalation, it not only infects organs like lungs, but also reaches highly protected organs like eyes through the blood-retinal barrier by infecting the cells lining this barrier.

This finding is important as we increase our understanding of the long-term effects of SARS-CoV-2 infection,” said Singh. “Earlier, researchers were primarily focused on the ocular surface exposure of the virus. However, our findings reveal that SARS-CoV-2 not only reaches the eye during systemic infection but induces a hyperinflammatory response in the retina and causes cell death in the blood-retinal barrier. The longer viral remnants remain in the eye, the risk of damage to the retina and visual function increases.”

Singh also discovered that extended presence of SARS-CoV-2 spike antigen can cause retinal microaneurysm, retinal artery and vein occlusion, and vascular leakage.

“For those who have been diagnosed with COVID-19, we recommend you ask your ophthalmologist to check for signs of pathological changes to the retina,” Singh said. “Even those who were asymptomatic could suffer from damage in the eyes over time because of COVID-19 associated complications.”

While viruses and bacteria have been found to breach the blood-retinal-barrier in immunocompromised people, this research is the first to suggest that the virus that causes COVID-19 could breach the barrier even in otherwise healthy individuals, leading to an infection that manifests inside the eye itself. Immunocompromised patients or those with hypertension or diabetes may experience worse outcomes if they remain undiagnosed for COVID-19 associated ocular symptoms.

“Now that we know the risk of COVID-19 to the retina, our goal is to better understand the cellular and molecular mechanisms of how this virus breaches the blood-retinal barrier and associated pathological consequences in hopes of informing development of therapies to prevent and treat COVID-19 induced eye complications before a patient’s vision is compromised,” Singh said.

Source: University of Missouri-Columbia

Categories : CancerTags :

Researchers Identify New Marker for Breast Cancer Prognosis

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Photo by National Cancer Institute on Unsplash

A protein called retinitis pigmentosa GTPase regulator interacting protein 1-like (RPGRIP1L) performs various functions that are important for development and for health throughout life, and mutations in the RPGRIP1L gene have been linked to different diseases. New research published in The FASEB Journal indicates that expression levels of the RPGRIP1L gene might serve as a new prognostic marker for individuals with invasive breast cancer.

When investigators examined breast tissue specimens from different women, they found that the expression of RPGRIP1L was elevated in invasive breast cancer specimens compared with normal breast tissue specimens. Also, among patients with invasive breast cancer, those with higher RPGRIP1L gene expression had shorter survival times than those with low expression. Furthermore, elevated expression of RPGRIP1L corresponded with a spectrum of unfavourable clinicopathological features such as the presence of more aggressive forms of cancer and larger tumours.

The researchers also identified 50 genes and 15 proteins whose expression was positively related to RPGRIP1L expression, with most of these proteins and genes being involved in different aspects of the immune response and metabolism.

Finally, the team found that 4 compounds used against cancer – abrine, epigallocatechin gallate, gentamicin, and tretinoin – showed potential for reducing the expression of RPGRIP1L in lab experiments.

“The findings of our research underscore the potential of RPGRIP1L as a significant prognostic biomarker for breast cancer and suggest the viability of novel therapeutic strategies that may modify disease progression, thus potentially enhancing survival rates among affected individuals,” said co–corresponding author Jie Zeng, PhD, of the First Affiliated Hospital of Hunan Normal University, in China.

Source: Wiley