Archive for month: July, 2024

Research on thousands of proteins measured from a drop of blood demonstrates the ability of proteins to predict the onset of many diverse diseases.

The research, published in Nature Medicine, was carried out as part of an international research partnership between GSK, Queen Mary University of London, University College London, Cambridge University and the Berlin Institute of Health at Charité Universitätsmedizin, Germany.

The researchers used data from the UK Biobank Pharma Proteomics Project (UKB-PPP), the largest proteomics study to date with measurements for approximately 3,000 plasma proteins from a randomly selected set of over 40,000 UK Biobank participants. The protein data is linked to the participants’ electronic health records. The authors used advanced analytical techniques to pinpoint, for each disease, a ‘signature’ of between the 5 and 20 proteins most important for prediction.

The researchers report the ability of protein ‘signatures’ to predict the onset of 67 diseases including multiple myeloma, non-Hodgkin lymphoma, motor neurone disease, pulmonary fibrosis, and dilated cardiomyopathy.

The protein prediction models out-performed models based on standard, clinically recorded information. Prediction based on blood cell counts, cholesterol, kidney function and diabetes tests (glycated haemoglobin) performed less well than the protein prediction models for most examples.

The patient benefits of measuring and discussing the risk of future heart attack and stroke (‘cardiovascular risk scores’) are well established. This research opens up new prediction possibilities for a wide range of diseases, including rarer conditions. Many of these can currently take months and years to diagnose, and this research offers wholly new opportunities for timely diagnoses.

These findings require validation in different populations including people with and without symptoms and signs of diseases and in different ethnic groups.

Lead author Professor Claudia Langenberg, Director of the Precision Healthcare University Research Institute (PHURI) at Queen Mary University of London and Professor of Computational Medicine at the Berlin Institute of Health at Charité Universitätsmedizin, said:

“Measuring one protein for a specific reason, such as troponin to diagnose a heart attack, is standard clinical practice. We are extremely excited about the opportunity to identify new markers for screening and diagnosis from the thousands of proteins circulating and now measurable in human blood. What we urgently need are proteomic studies of different populations to validate our findings, and effective tests that can measure disease relevant proteins according to clinical standards with affordable methods.”

First author Dr Julia Carrasco Zanini Sanchez, research student at GSK and the University of Cambridge at the time and now postdoctoral researcher at PHURI, said:

“Several of our protein signatures performed similar or even better than proteins already trialled for their potential as screening tests, such a prostate specific antigen for prostate cancer. We are therefore extremely excited about the opportunities that our protein signatures may have for earlier detection and ultimately improved prognosis for many diseases, including severe conditions such as multiple myeloma and idiopathic pulmonary fibrosis. We identified so many promising examples, the next step is to select high priority diseases and evaluate their proteomic prediction in a clinical setting.“

Co-lead author Dr Robert Scott, Vice President and Head of Human Genetics and Genomics, at GSK, said:

“A key challenge in drug development is the identification of patients most likely to benefit from new medicines. This work demonstrates the promise in the use of large-scale proteomic technologies to identify individuals at high risk across a wide range of diseases, and aligns with our approach to use tech to deepen our understanding of human biology and disease. Further work will extend these insights and improve our understanding of how they are best applied to support improved success rates and increased efficiency in drug discovery and development.”

Reference:

Carrasco-Zanini, J., Pietzner, M., Davitte, J. et al. Proteomic signatures improve risk prediction for common and rare diseases. Nat Med (2024). https://doi.org/10.1038/s41591-024-03142-z.

Patients living in “high-sun” climates may require higher doses of Botox to achieve good results in cosmetic treatment of facial lines and wrinkles, reports a study in the July issue of Plastic and Reconstructive Surgery®, the official medical journal of the American Society of Plastic Surgeons (ASPS). The journal is published in the Lippincott portfolio by Wolters Kluwer.

“In countries with higher sun exposure, higher doses of Botox may be needed to achieve the same degree of forehead muscle paralysis, compared to less-sunny countries,” comments lead author Kim L. Borsky, MBBS, MD, MRCS, of Stoke Mandeville Hospital, Aylesbury, UK. “Our results suggest that plastic surgeons may need to adjust their Botox dosing protocols to account for the effects of climate on the results of this cosmetic treatment.”

Could sun exposure affect responses to cosmetic Botox?

Administration of “injectables” is the most common minimally invasive cosmetic procedure performed by plastic surgeons. According to ASPS statistics, injection of neuromodulators such as botulinum toxin type A – best known by the brand name Botox – was performed more than 8.7 million times in 2022. Botox blocks nerve signals to the injected muscles, causing reversible muscle paralysis. This allows softening and relaxation of lines and wrinkles of the overlying skin.

Plastic surgeons have noticed variations in the improvement achieved by Botox injections. While several factors are known to affect the response – including muscle mass, gender, age, and ethnicity – other, unidentified factors may also play a role.

Could climate contribute to differences in the response to cosmetic Botox injection? Dr. Borsky and colleagues compared outcomes of Botox treatment in two groups of patients: a “high-sun” group of 292 women in the Mediterranean island nation of Malta and a “low-sun” group of 231 women treated in London, UK. Patients in Malta were treated during the summer months while the UK patients were treated in the winter months.

Botox treatments ‘may need to account for climate’

The patients underwent Botox injections into the glabellar muscles of the lower forehead; all treatments were performed by experienced plastic surgeons following a standardized technique. At follow-up visits, patients received “top-up” doses as needed to achieve “full clinical paralysis.” Total Botox dose needed to achieve this result was compared between the high-sun and low-sun groups.

The results showed a higher average total Botox dose in the high-sun group: 29.2 versus 27.3 units. Patients in Malta also received a higher average top-up dose: 2.24 versus 1.98 units. The differences in Botox dose remained significant after adjustment for age and other factors.

Why would patients in sunny climates need more Botox? Noting that the glabellar muscles are the main muscle group involved in squinting, Dr. Borsky and colleagues speculate that the difference may reflect greater development and functional activation of these muscles. Other possibilities include effects of higher temperatures or direct effects of sunlight on the response to Botox.

The researchers note that the small difference in their study isn’t likely to have a large impact on treatment costs, but it may have implications for training and treatment. “Rigid protocols about doses and distributions may lead to undertreatment if applied in sunnier climates,” Dr. Borsky and coauthors conclude. “Treatment protocols may need to account for the climate in which treatments are being undertaken to achieve more predictable results.” 

Reference:

Borsky, Kim L.,  Rodrigues, Jeremy N, Rodrigues, Raina, The Effect of Climate on the Dose Requirements of Botulinum Toxin A in Cosmetic Interventions, Plastic and Reconstructive Surgery, DOI: 10.1097/PRS.0000000000010913.

USA: Research on the pericapsular nerve group (PENG) block in total hip arthroplasty (THA) indicated no significant reduction in immediate postoperative pain or opioid use compared to conventional methods. However, patients who received the PENG block had shorter hospital stays and quicker mobilization times, likely influenced more by evolving discharge practices than direct pain management benefits.

Early natural menopause (early-M; <45 years of age) increases the risk of lung morbidities and mortalities in smokers. However, it is largely unknown whether early-M due to surgery demonstrates similar effects and whether menopausal hormone therapy (MHT) is protective against lung diseases.

The researchers conducted the study to assess the associations of early-M and MHT with lung morbidities and mortalities using the prospective Prostate, Lung, Colorectal and Ovarian (PLCO) trial.

The researchers aimed to  estimate the risk among 69 706 postmenopausal women in the PLCO trial, stratified by menopausal types and smoking status.

It was found that Early-M was associated with an increased risk of most lung disease and mortality outcomes in ever smokers with the highest risk seen for respiratory mortality (HR 1.98, 95% CI 1.34 to 2.92) in those with bilateral oophorectomy (BO). Early-M was positively associated with chronic bronchitis, and all-cause, non-cancer and respiratory mortality in never smokers with natural menopause or BO, with the highest risk seen for BO-respiratory mortality (HR 1.91, 95% CI 1.16 to 3.12). Ever MHT was associated with reduced all-cause, non-cancer and cardiovascular mortality across menopause types regardless of smoking status and was additionally associated with reduced risk of non-ovarian cancer, lung cancer (LC) and respiratory mortality in ever smokers. Among smokers, ever Menopausal hormone therapy use was associated with a reduction in HR for all-cause, non-cancer and cardiovascular mortality in a duration-dependent manner.

The study concluded that Smokers with early-Menopause should be targeted for smoking cessation and lung cancer screening regardless of menopause types. Menopausal hormone therapy users had a lower likelihood of dying from lung cancer and respiratory diseases in ever smokers.

Reference:

Gai X, Feng Y, Flores TM, et alEarly menopause and hormone therapy as determinants for lung health outcomes: a secondary analysis using the PLCO trialThorax Published Online First: 13 June 2024. doi: 10.1136/thorax-2023-220956

Researchers discovered that, in patients with atopic dermatitis, long-term use of oral corticosteroids was slightly associated with an increased risk for adverse events. This is an important finding that highlights the need for careful and close monitoring when prescribing and using oral corticosteroids in the treatment of AD. These findings were published in JAMA Network Open by Yong Hyun and colleagues.