Month: April 2022

Categories : Gender Injury & TraumaTags :

Low Sex Hormone Levels Linked to Rotator Cuff Tears

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Patients with lower levels of sex hormones are more likely to need to undergo surgery for rotator cuff tears, suggests a study in The Journal of Bone & Joint Surgery. 

Sex hormone deficiencies “was associated with a significantly increased incidence of RCR within [two] independent databases,” according to the new research by Peter N. Chalmers, MD, and colleagues at University of Utah. These findings add to previous evidence that hormone levels may be a systemic factor contributing to the development of rotator cuff tears, a common condition that is a major cause of shoulder pain.

The study used health insurance data for nearly 230 000 adults under age 65 who underwent surgery to repair a torn rotator cuff from 2008 through 2017. Patients were matched for age, sex, and type of insurance to patients who did not undergo rotator cuff surgery.

Patients undergoing rotator cuff repair had an average age of 54 years, and 58% were men. Most patient characteristics were similar between those who underwent rotator cuff repair and those who did not, except tobacco use, which was more common in the surgical cohort.

Dr Chalmers and colleagues found that 27% of women and 7% of men undergoing rotator cuff surgery had diagnosed sex hormone deficiency, compared with 20% and 4% respectively in the control group. Controlling for other factors, rotator cuff repair likelihood was 48% higher in women with oestrogen deficiency and 89% higher in men with testosterone deficiency.

To confirm their findings, the researchers then accessed the Veterans Administration Genealogy database which has data on millions of individuals. Here, they found that rotator cuff repair was about 2.5 times more likely for women with oestrogen deficiency and three times more likely for men with testosterone deficiency.

This study builds on a prior study by the same research group, which demonstrated that women with mutations in an oestrogen receptor gene were more likely to develop rotator cuff disease, with higher rates of failed rotator cuff surgery.

Despite limitations such as not accounting for hormone replacement therapy, the observed association between sex hormone deficiency and rotator cuff repair strongly supports the theory that low oestrogen and testosterone levels may contribute to the development of rotator cuff tears. The researchers concluded that “Future prospective studies will be necessary to understand the relationship of sex hormones to the pathophysiology of rotator cuff disease.”

Source: EurekAlert!

Categories : COVIDTags :

Kids are a Significant Source of COVID Spread in Households

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COVID spreads extensively in households, with children being a significant source of that spread. These are the findings from an antibody surveillance study published in CMAJ Open, which also shows that about 50% of household members were infected from the first-infected individual during the study period.

Although kids were less likely to spread the virus compared to adults, children and adults were equally likely to become infected from the first-infected individual.

The antibody surveillance study included 695 participants from 180 households in the Canadian city of Ottawa in Ontario, between September 2020 and March 2021. Included households had at least one member having had a confirmed COVID infection and at least one child within their household.

“Our study was conducted when we were dealing with a less transmissible virus and pandemic restrictions were strongly in place, and we still had a 50% transmission rate within households. Flash forward to where we are today with an extremely transmissible variant of COVID and the majority of pandemic restrictions lifted; it’s safe to say transmission rates will be higher even though we have a high vaccination rate amongst those who are eligible,” said Dr Maala Bhatt, the study’s lead author. 

“I know many want to ‘live with COVID’ and abandon the layers of protection that were previously mandated, but it’s important to be aware of the high transmissibility of this virus in closed, indoor settings, such as schools,” she cautioned.  “Our most vulnerable and our youngest children who are not yet able to be vaccinated are still at risk for COVID infection.”

In the Canadian province of Eastern Ontario, where the study was done, COVID is on the rise once again. Three-quarters of all children admitted to CHEO with COVID have come during the Omicron wave. Since the beginning of January this year a third of the roughly 4900 monthly visits to the Emergency Department were for COVID-related symptoms.

The study hypothesised that children would act as “an even greater source of spread within households with the emergence of more infectious variants.” Children also have “considerable potential to spread” in settings such as school and daycare, where they congregate indoors for long periods, especially now when masking is not required in many jurisdictions.

“While we’re lucky hospitals aren’t currently overloaded, emergency departments are and positivity rates are on the rise, even amongst children,” said Dr Bhatt, paediatric emergency physician and Director of Emergency Medicine Research at CHEO and an Investigator at the CHEO Research Institute.

“We continue to learn more about COVID and its potential long-term health impacts, and we still aren’t clear about how long immunity lasts; these are all things researchers continue to study.”

Source: University of Ottawa

Categories : Cardiovascular DiseaseTags :

Thoracic Aorta Diameter Can Predict Cardiovascular Risk

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Anatomical model of a human heart
Photo by Robina Weermeijer on Unsplash

A new study in the journal Radiology has found that the diameter of the thoracic aorta can be a biomarker for heart attacks and other adverse cardiovascular events in women and men, and has the advantage of being simple to add on to existing screening.

The thoracic aorta is divided into an ascending aorta that rises from the left ventricle of the heart and a descending aorta in the back of the chest.

While the thoracic aorta grows with age, but changes of vessel size and structure, a phenomenon known as vascular remodelling, have a systemic nature involving haemodynamic and biological processes that are also linked to cardiovascular disease.

“While enlargement of the thoracic aorta is a frequent finding in clinical practice, few longitudinal data regarding its long-term prognosis for major cardiovascular disease outcomes at the population level exist,” said study senior author Maryam Kavousi MD, PhD, from University Medical Center Rotterdam.

Dr Kavousi and colleagues assessed these associations in 2178 participants from the population-based Rotterdam Study. Participants underwent multi-detector CT scans between 2003 and 2006 and were followed for an average of 9 years. Thoracic aorta diameters were indexed for body mass index (BMI).

Larger BMI-indexed ascending and descending thoracic aortic diameters were significantly associated with increased risk of adverse cardiovascular outcomes like stroke and death in both women and men.

“Our results suggest that imaging-based assessment of diameter of thoracic aorta can be considered as a risk marker for future cardiovascular disease,” Dr Kavousi said.

In women, greater ascending aortic diameter was associated with 33% higher cardiovascular mortality risk. There seems to be a sex difference in remodelling of the ageing aorta, with faster deterioration in women.

“Ageing could affect aortic health and structure more adversely in women than in men,” Dr Kavousi said.

The study findings suggest that cardiovascular risk assessment associated with thoracic aortic size among asymptomatic women and men could lead to effective, sex-specific prevention strategies.

“As the aortic diameter is significantly related to body size, use of aortic diameters indexed for body measurements could improve its prognostic value for cardiovascular outcomes,” Dr Kavousi said.

Measurement of thoracic aorta size is an easy addition to current screening, the researchers said. The study made use of cardiac CT scans that are already commonly used to assess coronary calcium. Thoracic aortic diameter could also be measured routinely, for example as part of CT-based lung cancer screening.

The current study was based on a single CT-based assessment of thoracic aorta among a large group of participants from the general population, followed up for nine years for incidence of cardiovascular outcomes and mortality. The researchers have recently repeated the CT-based assessment of thoracic aorta among these participants after a median of 14 years.

“This provides an exciting and unique opportunity to study sex-specific risk profiles and patterns of growth in thoracic aorta in the general population,” Dr Kavousi said.

Source: Radiological Society of North America

Categories : Injury & TraumaTags :

Greater Concussion Risk in Fighters Who Cut Weight for a Bout

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There is more risk of suffering concussions or being misdiagnosed with head trauma is greater among fighters who rapidly cut weight before bouts, usually by dehydrating, researchers have revealed for the first time.

More than 60% of athletes in combat sports such as boxing and mixed martial arts (MMA) reported that their symptoms worsened after they dehydrated to make strict weight classes.

These controversial weight cutting techniques involve stop drinking water and endure long periods in saunas.

MMA athletes reported concussion severity to be 40% higher compared to other sports, particularly boxing – believed to be due to the mix of striking and contact with the ground.

Published in the Clinical Journal of Sports Medicine, the study comes after a series of tragedies associated with weight cuts, with some athletes even dying in the attempt to achieve a perceived competitive edge, by competing in a smaller weight class.

They found that as competitors dramatically dehydrate themselves to meet stringent weight classes, the associated symptoms may ‘muddy the waters’ of baseline concussion testing, due to similar symptoms.

This is because the symptoms of hypohydration – where competitors enter a water deficit – match concussive signs, such as dizziness, headaches, and lethargy.

This study has spurred further probes into the neurological implications of rapid weight loss. The researchers have called on governing bodies to check fighters’ hydration levels before fights.

Researcher Nasir Uddin, from St Mary’s University, said: “This study shows that current concussion testing does not account for the crossover of symptoms from being dehydrated, and is potentially putting fighters at risk.

“Not only is cutting weight through dehydration in and of itself dangerous, but it might actually exacerbate concussion symptoms and, even more concerningly, means medical professionals may actually misdiagnose it.

“Going forward, governing bodies should ensure hydration and baseline concussion symptoms are taken into account before and after bouts.”

The study surveyed more than 130 anonymous athletes representing six combat sports, all aged 18 or above and who had previously cut weight.

It also found that 65% of the fighters had an experience of a weight cut “not going to plan”, suffering a lack of energy, strength, power, coordination or increased susceptibility to being ‘rocked’ during a bout.

This means the dangerous practice may not offer a competitive advantage after all.

Dr Jamie Tallent, from the University of Essex, said: “This is perhaps the most surprising finding that not only are weight cuts dangerous – they leave fighters at a disadvantage more often than not and may exacerbate the risks of being further injured.”

Source: University of Essex

Categories : CancerTags :

Why Some Lung Cancer Patients Stop Responding to Treatment

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Anatomical model of lungs
Photo by Robina Weermeijer on Unsplash

Published in Cancer Research, researchers have discovered why some patients with nonsmall cell lung cancer stop responding to treatment with tyrosine kinase inhibitors (TKIs): an epigenetic switch is flipped, reactivating genes that inhibit the effect of these drugs.

TKIs, specifically epidermal growth factor receptor inhibitors, are typically used to treat people with nonsmall cell lung cancer, a prevalent and usually incurable type of cancer that accounts for 80–85% of lung cancers. About 15–20% of these patients will become resistant to these standard treatments, resulting in their eventual death. This is because the cells develop a mutation that leads to resistance. But about half of the remaining resistant patients remain unexplained. 

Cellular biologist Andrea Kasinski and her lab have found that the cause involves epigenetics. When cells lose a histone called methyltransferase (KMT5C), genes that KMT5C were repressing instead become expressed, leading to resistance to epidermal growth factor receptor inhibitors. This could open up development of new therapeutics and gives researchers and doctors a deeper insight into the biology and progression of cancers, especially the role that epigenetic-modifying proteins play in drug resistance, a poorly understood phenomenon.

“For the majority of genes that contribute to cancer, we’re not sure how they work yet,” Kasinski said. “And for many, we don’t have a way to therapeutically target them. Research like this, that helps us understand how those genes work to determine cancer outcomes, adds to our understanding of the network. This knowledge will ultimately lead us to better therapeutics.”

Source: Purdue University

Categories : Mental HealthTags :

For Some, It may be Daydreaming – not ADHD

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Maladaptive daydreaming (MD) may be a better diagnosis for some people than ADHD, researchers argue in a paper in the Journal of Clinical Psychology. MD is a condition whereby people slip into involved highly detailed and realistic daydreams that can last hours at the cost of normal functioning – but it is not yet recognised as a psychiatric disorder.

Dr Nirit Soffer-Dudek of the Consciousness and Psychopathology Laboratory in the Department of Psychology at BGU is one of the leadings experts on the condition and wants to have MD added to the next edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM VI), by promoting rigorous research into this condition.

Explaining the concept of MD, Dr Soffer-Dudek said: “Some individuals who become addicted to their fanciful daydreams experience great difficulty in concentrating and focusing their attention on academic and vocational tasks, yet they find that an ADHD diagnosis and the subsequent treatment plan does not necessarily help them. Formally classifying MD as a mental disorder would enable psychological practitioners to better assist many of their patients.”

Previous studies had found high levels of ADHD in those also presenting with MD, thereby raising the question of whether MD was separate from ADHD. In the current study, the investigators assessed 83 adults diagnosed with ADHD for inattention symptoms, MD, depression, loneliness, and self-esteem. Of those, about 20% met the proposed diagnostic criteria for MD, with significantly higher rates of depression, loneliness, and lowered self-esteem, compared to those with ADHD that did not meet criteria for MD.

“Our findings suggest that there is a subgroup of those diagnosed with ADHD who would benefit more from a diagnosis of MD,” concluded Dr Soffer-Dudek.

Source: Ben-Gurion University of the Negev

Categories : Allergies Cardiovascular DiseaseTags :

Allergies Linked to Increased Cardiovascular Risk

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Runny nose and sneezing symptoms
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A national US health survey has revealed that adults with allergies are at an increased risk of hypertension and coronary heart disease, with the biggest risk increase seen in Black male adults. The study is presented at ACC Asia 2022 Together with the Korean Society of Cardiology Spring Conference.

“For patients with allergic disorders, routine evaluation of blood pressure and routine examination for coronary heart disease should be given by clinicians to ensure early treatments are given to those with hypertension or coronary heart disease,” said Yang Guo, PhD, the study’s lead author.

An association between allergic disorders and cardiovascular disease was detected in prior research, findings which remained controversial, Dr Guo explained. The present study sought to determine whether an increased cardiovascular risk exists in adults with allergic disorders.

The study used 2012 data from the National Health Interview Survey (NHIS), a cross-sectional survey of the US population. In the allergic group were adults with at least one allergic disorder, including asthma, respiratory allergy, digestive allergy, skin allergy and other allergy. The study included a total of 34 417 adults, over half of whom were women, average age 48.5 years. The allergic group included 10 045 adults. The researchers adjusted for age, sex, race, smoking, alcohol drinking and body mass index; they also examined subgroups stratified by demographic factors.

Having a history of allergic disorders was found to be associated with increased risk of developing hypertension and coronary heart disease. Further analysis showed that individuals with a history of allergic disorders between ages 18 and 57 had a higher risk of hypertension. An increased risk of coronary heart disease was seen in male Black/African American participants between ages 39-57. Asthma was the largest contributor of risk of hypertension and coronary heart disease.

Dr Guo said that to confirmed these findings, large cohort studies with long-term follow-up are required. Discovering the underlying mechanism could also help with management.

Source: American College of Cardiology

Categories : CancerTags :

Leukaemia Drug Clofarabine Might Also Treat Bladder Cancer

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Woman using lab equipment
Source: NCI on Unsplash

A drug screen on various cancer cell lines revealed hundreds of compounds with inhibitory effects on cancer, and one in particular, the leukaemia drug clofarabine, showed effectiveness in two specific types of bladder cancer. The study was published in the journal European Urology.

A joint study group conducted a drug screen which investigated the effects of over 1700 chemical compounds on 23 cell lines representing different stages and subtypes of bladder cancer. From this, the researchers identified more than 470 substances with inhibitory effects. These included a large number of drugs already used for cancers, but also medications for other diseases, such as malaria, parasitic diseases and various mental disorders.

One of these compounds, clofarabine, an antimetabolite drug currently used to treat childhood leukaemia, was studied in more detail. For this purpose, the researchers developed models from patient material representing different types of bladder cancer. Besides ‘conventional’ urothelial carcinoma, they were also able to establish an animal model for sarcomatoid carcinoma – a rare subtype of bladder cancer, for which there is currently no effective chemotherapy. 

Describing the results, first author Iris Ertl said: “We found that clofarabine induced complete remission in mice with conventional urothelial carcinoma and massive, sustained tumour shrinkage in animals with sarcomatoid carcinoma, while not causing any apparent side effects.” 

Next steps will be clinical trials in which patients with metastatic bladder cancer who cannot receive cisplatin-based therapy, will be treated with clofarabine prior to radical cystectomy. Shahrokh Shariat explains: “Our discovery was made possible by the close interdisciplinary collaboration with CeMM and the Center of Cancer Research. We very much look forward to continuing to work with our partners to incorporate our findings into clinical practice.”

Source: Medical University of Vienna

Categories : Diseases, Syndromes and ConditionsTags :

Zika Can Mutate to Increase its Infectivity

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Mosquito, a malaria parasite vector
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Researchers have found that Zika virus has the potential to mutate and increase its infectivity, potentially breaking through pre-existing immunity.

“The world should monitor the emergence of this Zika virus variant,” said LJI Professor Sujan Shresta, PhD, who co-led the La Jolla Institute for Immunology (LJI) study which is published in Cell Reports.

A mosquito-borne virus, symptoms of Zika infection are usually mild in adults. However, in a developing foetus, infection can cause birth defects such as microcephaly.

Zika virus and dengue virus occur together in a number of countries. Both viruses are a mosquito-borne flavivirus, sharing biological similarity:  similar enough that prior dengue exposure can offer immune protection against Zika.

“In areas where Zika is prevalent, a vast majority of people have already been exposed to dengue virus and have both T cells and antibodies that cross-react,” said Prof Shresta.

Unfortunately, both viruses share the trait of rapid mutation. “Dengue and Zika are RNA viruses, which means they can change their genome,” she further explained. “When there are so many mosquitoes and so many human hosts, these viruses are constantly moving back and forth and evolving.”

To study Zika’s fast-paced evolution, the researchers simulated infection cycles that repeatedly switched back and forth between mosquito cells and mice. This painted a picture of how Zika virus naturally evolves as it encounters more hosts.

The LJI team found that an easy change of a single amino acid allows the virus to make more copies of itself — and help infections take hold more easily. This mutation (called NS2B I39V/I39T mutation) boosts viral replication in both mice and mosquitoes – and also in human cells.

“This single mutation is sufficient to enhance Zika virus virulence,” commented study first author Jose Angel Regla-Nava, PhD. “A high replication rate in either a mosquito or human host could increase viral transmission or pathogenicity – and cause a new outbreak.”

Prof Shresta added, “The Zika variant that we identified had evolved to the point where the cross-protective immunity afforded by prior dengue infection was no longer effective in mice. Unfortunately for us, if this variant becomes prevalent, we may have the same issues in real life.”

To help prepare for this variant, Dr Shresta’s laboratory is already looking at ways to tailor Zika vaccines and treatments that counteract this dangerous mutation.

“We want to understand at what point in the viral life cycle this mutation makes a difference,” said Dr Shresta.

Source: La Jolla Institute for Immunology

Categories : COVID GeneticsTags :

Rare COVID Vaccine Blood Clots May Result from Genetics

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Scientists have discovered that the rare blood clot side-effect associated with some COVID vaccines could be the result of a specific gene variant, which could make a genetic screening test possible.

Vaccine-induced thrombotic thrombocytopenia (VITT), a rare disorder causing thrombosis and thrombocytopenia (low blood platelet counts), was linked to AstraZeneca’s COVID vaccine in early 2021, leading some countries to pause or restrict its use. It is also associated with the Johnson & Johnson vaccine, which also uses a viral vector.

Now, a new study may help to explain what’s causing the rare side effect. The study by Flinders University and SA Pathology is now available on the medRxiv preprint server and is awaiting peer review.

Examining five unrelated individuals who all had the clotting complication after vaccination, the researchers found that all of the patients had unusually structured antibodies against a protein called platelet factor 4 (PF4), which is involved in blood clotting.

In addition, all five shared a specific version of a gene responsible for producing these antibodies.

“We knew previously that PF4 was directly involved in the clotting disorder, and we knew that aberrant antibodies against PF4 are responsible, but what we don’t know is how and why some people develop them,” explained lead author Dr Jing Jing Wang.

The antibodies were all found to be derived from the same amino acid sequence. The researchers then found that all of the patients carried a specific variant of one gene, called IGLV3-21*02, most commonly occurring in people of European descent.

“The other specific amino acid sequences of these antibodies from each patient were derived from separate basic sequences but had all evolved to carry very similar properties, making them very potent attackers of the PF4 protein,” explained research team leader Professor Tom Gordon.

“Together, this suggests that it is the combination of a variant in a gene and the evolution of this antibody towards targeting the PF4 protein in a destructive manner, which is leading to this harmful side-effect.”

Though why the antibody is found in such a tiny number of vaccine recipients remains unknown, the identification of the gene could enable a genetic screening tool to identify patients who are at risk of this severe complication.

“It also provides a unique opportunity for targeted, specific therapy development aimed at neutralising this highly damaging but very specific antibody,” said Dr Wang.

Source: Flinders University