Year: 2022

Categories : CancerTags :

Adverse Effects of Antibody Drug Conjugates for Cancer Treatment

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Intravenous IV drip
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Over the past two decades, numerous complex cancer therapies called antibody drug conjugates (ADCs) have been tested in clinical trials and approved for use in patients. An analysis of multiple scientific databases has found that some ADCs have higher rates of adverse effects. The findings were reported in the journal CANCER.

An ADC has a complex structure comprised of a monoclonal antibody (MoAb) that targets a protein expressed on cancer cells, a toxic compound to kill the targeted cells (also called a payload or warhead), and a linker to join the two. The clinical efficacy and toxicity of ADCs are affected by each component. Data have established that ADCs as anticancer therapeutics have a unique mechanism of action, which includes the targeted delivery and release of its payload at the tumours site through MoAb antibody components, thus exerting simultaneous roles as both targeted therapy and chemotherapy

In 2000, gemtuzumab ozogamicin was the first ADC approved by the US Food and Drug Administration, and more than a dozen ADCs have been approved worldwide to date. To investigate the side effects associated with different ADCs, a team led by Prof Hong Zhu of Xiangya Hospital, Central South University, in China, conducted a systematic review and meta-analysis of published clinical trials of ADCs that reported treatment-related toxicities.

The researchers found 2511 records of 169 relevant trials involving 22 492 patients. The incidence of treatment-related adverse events was 91.2% for all events and 46.1% for serious adverse events (grade 3 or higher). The most common adverse events overall were lymphopenia, nausea, neutropenia, vision blurriness, and peripheral neuropathy. The most common serious adverse events were neutropenia, hypaesthesia, thrombocytopenia, neutropenia with fever, and lymphopenia. Certain ADCs were linked with higher average incidences of adverse events.

“Different ADCs appear to vary in their treatment-related adverse events. Our results provide an important reference for clinicians and patients on how to address ADCs’ toxicity in clinical practice,” said Prof Zhu.

Source: Wiley

Categories : DentistryTags :

Vaping Device Use Tied to Increased Risk of Developing Cavities

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Research published in The Journal of the American Dental Association found patients who said they used vaping devices were more likely to have a higher risk of developing cavities. The findings of this study on the association between vaping and risk of caries serve as an alert that this once seemingly harmless habit may be very detrimental, says Karina Irusa, assistant professor of comprehensive care at Tuftst University and lead author on the paper.

Over the last few years, public awareness has increased about the dangers of vaping to systemic health, particularly after the use of vaping devices was tied to lung disease. Some dental research has shown ties between e-cigarette use and increased markers for gum disease, and, separately, damage to the tooth’s enamel, its outer shell. But relatively little emphasis has been placed on the intersection between e-cigarette use and oral health, even by dentists, says Irusa.

Irusa says that the finding may be just a hint of the damage vaping causes to the mouth. “The extent of the effects on dental health, specifically on dental decay, are still relatively unknown,” she says. “At this point, I’m just trying to raise awareness,” among both dentists and patients.

This study, Irusa says, is the first known specifically to investigate the association of vaping and e-cigarettes with the increased risk for getting cavities. She and her colleagues analysed data from more than 13 000 patients older than 16 who were treated at Tufts dental clinics from 2019–2022.

Irusa found a significant difference in dental caries risk levels between the e-cigarette/vaping group and the control group. Some 79% of the vaping patients were categorised as having high-caries risk, compared to just about 60% of the control group. The vaping patients were not asked whether they used devices that contained nicotine or THC, although nicotine is more common.

“It’s important to understand this is preliminary data,” Irusa says. “This is not 100% conclusive, but people do need to be aware of what we’re seeing.” Further studies need to be done, and Irusa wants to take a closer look at how vaping affects the microbiology of saliva.

One reason why e-cigarette use could contribute to a high risk of cavities is the sugary content and viscosity of vaping liquid, which, when aerosolised and then inhaled through the mouth, sticks to the teeth. (A 2018 study published in the journal PLOS One likened the properties of sweet-flavoured e-cigarettes to gummy candies and acidic drinks.) Vaping aerosols have been shown to change the oral microbiome making it more hospitable to decay-causing bacteria. It’s also been observed that vaping seems to encourage decay in areas where it usually doesn’t occur – such as the bottom edges of front teeth. “It takes an aesthetic toll,” Irusa says.

The Tufts researchers recommend that dentists should routinely ask about e-cigarette use as part of a patient’s medical history, including paediatric dentists who see adolescents. According to the FDA/CDC, 7.6% of middle- and high-school students said they used e-cigarettes in 2021.

The researchers also suggest patients who use e-cigarettes should be considered for a “more rigorous caries management protocol,” which could include prescription-strength fluoride toothpaste and fluoride rinse, in-office fluoride applications, and checkups more often than twice a year.

“It takes a lot of investment of time and money to manage dental caries, depending on how bad it gets,” Irusa says. “Once you’ve started the habit, even if you get fillings, as long as you continue, you’re still at risk of secondary caries. It’s a vicious cycle that will not stop.”

Source: Tufts University

Categories : CancerTags :

Irradiating only Select Lymph Nodes Reduces Cancer Recurrences

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MRI or CT machine
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A new study published in Nature Communications suggests that the recurrence of certain cancers can be significantly decreased by only irradiating a select set of lymph nodes near a tumour instead of all of them. By doing so, some immune cells that can recognise the cancer are able to survive.

“Doctors have traditionally irradiated all the lymph nodes surrounding a tumour in a process called ‘elective nodal irradiation,'” said senior author Sana Karam, MD, PhD, associate professor of radiation oncology at the University of Colorado School of Medicine. “But the problem with this scorched-earth approach in the era of immunotherapy is that doing so also eliminates the source of immune cells for the immunotherapy to work on. Lymph nodes are the hub for priming and expanding the major immune cells that can go and fight the cancer.”

Karam and her team learned that irradiating all of the lymph nodes around a tumour significantly decreased immune memory and antigen spread, creating a much greater risk of metastasis. “That was an unexpected finding,” says Karam.

The team tested this theory pre-clinically on several different tumour models of head and neck, along with a breast cancer and melanoma model. The results remained the same: when radiation killed immune cells that recognised the cancer, the patient’s immune system lost the ability to fight the cancer systemically.

On the other hand, the researchers found that irradiating certain lymph nodes known as sentinel lymph nodes was absolutely critical. Failure to irradiate those resulted in recurrence nearby.

“This study confirms why elective nodal irradiation has long been the clinical standard of care, as it does decrease regional recurrence,” said Laurel B. Darragh, the paper’s first author and an MD/PhD student in Dr. Karam’s lab. “But it also shows that to combine radiation with immunotherapy effectively, we need to re-evaluate our strategies and restrict nodal irradiation to the sentinel lymph nodes. This eliminates regional neck recurrence, and far away spread, while preserving long-term, systemic immune response.”

The findings were corroborated by data from a recent human patient clinical trial where pre-surgical radiation was limited to the gross tumour and the sentinel lymph nodes while avoiding all other lymph nodes so as to sustain immune memory. Researchers found that the immune system in these patients was highly activated, which has been shown to correlate with a better prognosis.

“We’re hopeful that this data will set the stage for future clinical trial design, not only reducing patients’ side effects but also improving long-term outcomes,” said Karam.

Source: University of Colorado Anschutz Medical Campus

Categories : Injury & TraumaTags :

Elite Athletes Have an Osteoarthritis Risk from Sports-related Injuries

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Elite retired sportspeople who had experienced a sports-related injury had a higher chance of knee and hip osteoarthritis when compared with the general population, according to a two-part study reported in the British Journal of Sports Medicine.

One in four retired Olympians reported a diagnosis of osteoarthritis, researchers have found. The athletes – who had competed at an Olympic level in 57 sports including athletics, rowing and skiing – also had an increased risk of lower back pain overall, and shoulder osteoarthritis after a shoulder injury.

Researchers hope the findings will help develop new approaches in injury prevention for the benefit of athletes now and in retirement.

The study is the largest international survey of its kind, and the first to observe the consequences of osteoarthritis and pain in different joints from retired elite athletes across different summer and winter Olympic sports.

Researchers surveyed 3357 retired Olympians aged around 45 on injuries and the health of their bones, joints, muscles and spine. They were also asked if they were currently experiencing joint pain, and if they had an osteoarthritis diagnosis. A comparison group of 1735 people aged around 41 from the general population completed the same survey.

Researchers used statistical models to compare the prevalence of spine, upper limb and lower limb osteoarthritis and pain in retired Olympians with the general population.

The team considered factors that could influence the risk of pain and osteoarthritis such as injury, recurrent injury, age, sex and obesity.

They found that the knee, lumbar spine and shoulder were the most injury prone areas for Olympians. These were also among the most common locations for osteoarthritis and pain.

After a joint injury the Olympians were more likely to develop osteoarthritis than someone sustaining a similar injury in the general population, the research found

The sportspeople also had an increased risk of shoulder, knee, hip and ankle and upper and lower spine pain after injury, although this did not differ with the general population.

Dr Debbie Palmer, of the University of Edinburgh’s Moray House School of Education and Sport, said: “High performance sport is associated with an increased risk of sport-related injury and there is emerging evidence suggesting retired elite athletes have high rates of post-traumatic osteoarthritis.

“This study provides new evidence for specific factors associated with pain and osteoarthritis in retired elite athletes across the knee, hip, ankle, lumbar and cervical spine, and shoulder, and identifies differences in their occurrence that are specific to Olympians.”

Researchers say the study may help people make decisions about recovery and rehabilitation from injuries in order to prevent recurrences, and to inform prevention strategies to reduce the risk and progression of pain and OA in retirement.

Source: University of Edinburgh

Categories : Pain ManagementTags :

Vitamin D is no Help for Statin Muscle Pains, Study Finds

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Vitamin D pills
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Some clinicians have recommended vitamin D supplements to ease the muscle aches of patients taking a statin, but a new study published in the journal JAMA Cardiology shows the vitamin appears to have no substantial impact.

While non-randomised studies have reported vitamin D to be an effective treatment for statin-associated muscle symptoms, the new study, which is the first randomised clinical trial to look at the effect of vitamin D on statin-associated muscle symptoms, was large enough to rule out any important benefits.

In the randomised, double-blind trial, 2083 participants took either 2000 units of vitamin D supplements daily or a placebo. The study found participants in both categories were equally likely to develop muscle symptoms and discontinue statin therapy.

Over 4.8 years of follow-up, statin-related muscle pain was reported by 31% of the participants assigned vitamin D and 31% assigned a placebo.

“We had high hopes that vitamin D would be effective because in our clinic and across the country, statin-associated muscle symptoms were a major reason why so many patients stopped taking their statin medication,” said senior author Dr Neil Stone, professor at Northwestern University. “So, it was very disappointing that vitamin D failed a rigorous test. Nevertheless, it’s important to avoid using ineffective treatments and instead focus on research that can provide an answer.”

Statins and vitamin D supplements are two of the most commonly used medications in American adults. About 30 to 35 million Americans are prescribed statins, and about half of the population aged 60 and older take a vitamin D supplement.

“We took advantage of a large placebo-controlled randomised trial to test whether vitamin D would reduce statin-associated muscle symptoms and help patients keep taking their statins,” said lead study author Dr Mark Hlatky, a professor of health policy and cardiovascular medicine at Stanford. “The placebo control in the study was important because if people think vitamin D is supposed to reduce their muscle pains, they just might feel better while taking it, even if vitamin D has no specific effect.”

Trial was a sub study within a larger clinical trial

The 2083 patients were among the larger cohort of participants in the VITamin D and Omega-3 Trial (VITAL), which randomised nearly 26 000 participants to double-blind vitamin D supplementation to determine whether it would prevent cardiovascular disease and cancer. This provided researchers a unique opportunity to test whether vitamin D reduces muscle symptoms among participants who initiated statins during the follow-up period of the larger VITAL trial. The mean age of the study participants was 67, and 51% were women.

“Randomised clinical trials are important because many very good ideas don’t work as well as we had hoped when they are put to the test,” Hlatky said. “Statistical associations do not prove a cause-and-effect relationship. Low levels of vitamin D are associated with many medical problems, but it turns out that giving people vitamin D does not generally fix those problems.”

For patients who report statin-associated muscle pains

Dr Stone noted that sometimes the secret for understanding patients who have difficulty with statins is analysing other medications they’re taking, determining whether or not they have associated metabolic or inflammatory conditions, counselling them on their ability to hydrate adequately and, importantly, discussing “pill anxiety.”

“For those who have difficulties with statins, a systematic appraisal by a physician with experience in dealing with these matters is still very important,” Stone said.

Source: Northwestern University

Categories : Mental Health NeurologyTags :

How Breathing Influences the Brain to Shape Mood and Behaviour

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Depiction of a human brain
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A study published in the journal Psychological Review describes a possible mechanism by which breathing influences the brain and how breathing exercises influence mood. The researchers synthesised results from more than a dozen studies with rodent, monkey, and human brain imaging, and used it to propose a new computational model that explains how our breathing influences the brain’s expectations.

“What we found is that, across many different types of tasks and animals, brain rhythms are closely tied to the rhythm of our breath. We are more sensitive to the outside world when we are breathing in, whereas the brain tunes out more when we breathe out. This also aligns with how some extreme sports use breathing, for example professional marksmen are trained to pull the trigger at the end of exhalation,” explains Professor Micah Allen from the Department of Clinical Medicine at Aarhus University.

The study suggest that breathing is more than just something we do to stay alive, explains Prof Allen.

“It suggests that the brain and breathing are closely intertwined in a way that goes far beyond survival, to actually impact our emotions, our attention, and how we process the outside world. Our model suggests there is a common mechanism in the brain which links the rhythm of breathing to these events.”

Breathing can affect our mental health

Understanding how breathing shapes our brain, and by extension, our mood, thoughts, and behaviours, is an important goal in order to better prevent and treat mental illness.

“Difficulty breathing is associated with a very large increase in the risk for mood disorders such as anxiety and depression. We know that respiration, respiratory illness, and psychiatric disorders are closely linked. Our study raises the possibility that the next treatments for these disorders might be found in the development of new ways to realign the rhythms of the brain and body, rather than treating either in isolation,” explains Micah Allen.

The new study sheds light on how the brain its possible to stabilise the mind through breathing exercises. It suggests that there are three pathways in the brain that control this interaction between breathing and brain activity. It also suggests that our pattern of breathing makes the brain more “excitable,” meaning neurons are more likely to fire during certain times of breathing.

Prof Allen says that research is underway into investigating how different kinds of emotional and visual perception are influenced by breathing in the brain, as well as the impact of long COVID.

Source: Aarhus University

Categories : Cancer ExerciseTags :

Exercise Improves Quality of Life in Breast Cancer Radiotherapy

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Tired woman after exercise
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Radiotherapy is an important part of breast cancer treatment but can lead to cancer-related fatigue and negatively impact patients’ health-related quality of life. Fortunately, latest research by has revealed exercise may make radiotherapy more tolerable for patients, offering benefits for their emotional, physical and social wellbeing.

Researchers at Edith Cowan University (ECU) included 89 women in the study, with 43 completing a home-based 12-week program, consisting of a weekly exercise regime of one to two resistance training sessions and an accumulated 30–40 minutes of aerobic exercise. The 46 controls did not participate in the exercise regime.

The results, published in Breast Cancer, showed that patients who exercised recovered from cancer-related fatigue quicker during and after radiotherapy compared to the control group and saw a significant increase in health-related quality of life post radiotherapy with no reported adverse effects.

Study supervisor Professor Rob Newton said this showed home-based resistance and aerobic exercise during radiotherapy is safe, feasible and effective in accelerating recovery from cancer-related fatigue and improving health-related quality of life.

“A home-based protocol might be preferable for patients, as it is low-cost, does not require travel or in-person supervision and can be performed at a time and location of the patient’s choosing,” he said.

“These benefits may provide substantial comfort to patients.”

Important changes observed

Australia’s current national guidelines for cancer patients recommend moderately intense aerobic exercise for 30 minutes per day, five days a week, or vigorously intense aerobic exercise for 20 minutes a day for three days a week.

They also call for 8–10 strength-training exercises with 8–12 repetitions per exercise, for two-to-three days per week.

However, study lead Dr Georgios Mavropalias said benefits were still observed with less exercise.

“The amount of exercise was aimed to increase progressively, with the ultimate target of participants meeting the national guideline for recommended exercise levels,” he said.

“However, the exercise programmes were relative to the participants’ fitness capacity, and we found even much smaller dosages of exercise than those recommended in the national guidelines can have significant effects on cancer-related fatigue and health-related quality of living during and after radiotherapy.”

The study also found participants good adherence to exercise programmes once they started. The exercise group reported significant improvements in mild, moderate and vigorous physical activity up to 12 months after the supervised exercise programme finished.

“The exercise programme in this study seems to have induced changes in the participants’ behaviour around physical activity,” Dr Mavropalias said.

“Thus, apart from the direct beneficial effects on reduction in cancer-related fatigue and improving health-related quality of life during radiotherapy, home-based exercise protocols might result in changes in the physical activity of participants that persist well after the end of the program.”

Source: Edith Cowan University

Categories : Ethics and Law Medical IndustryTags :

Theranos Founder Elizabeth Holmes Sentenced to 11 Years for Fraud

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Theranos’s Elizabeth Holmes in 2016
Credit: Tali Mackay at English Wikipedia, CC 4.0 license.

After a trial stretching out from before the COVID pandemic, Elizabeth Holmes, the former CEO of diagnostic biotech startup Theranos, has been sentenced to 11 years after being found guilty of fraud.

In 2018, she was indicted along with Ramesh “Sunny” Balwani on four counts of wire fraud and conspiracy to commit wire fraud in connection with the collapse of Theranos, and was found guilty in January this year. She had been seeking a retrial since she had been contacted by a key witness, former Theranos lab director Adam Rosendorff, who she claimed had recanted statements made under oath.

Before Theranos’s collapse, Rosendorff had previously supplied information for an investigative series into the struggling biotech firm’s Previously, the university dropout had been widely lauded as an innovator and an inspiration for women in technology.

In his remarks during the sentencing of Holmes, US District Judge Edward Davila said, “The tragedy of this case is that Ms. Holmes is brilliant. She had creative ideas. She is a big thinker. She was a woman moving into an industry that was dominated by, and let’s face it, male ego. That young women entrepreneurs are regrettably denied access to, but she made that.”

Judge Davila sentenced her to 135 months (11 years and three months) in prison. Holmes will report to serving her sentence on April 27, 2023, at a minimum-security women’s prison less than 160km from her native Houston, Texas.

Categories : HIVTags :

Infection by HIV Leaves a ‘Memory’ in Cells

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HIV Infecting a T9 Cell. Credit: NIH

Despite the benefits of antiretroviral therapy, people living with HIV often suffer from chronic inflammation, increasing the risk of developing comorbidities such as cardiovascular disease and neurocognitive dysfunction. Now, a new study in Cell Reports explains why chronic inflammation may be happening and how suppression or even eradication of HIV in the body may not resolve it.

In the study, researchers from the George Washington University show how an HIV protein permanently alters immune cells in a way that causes them to overreact to other pathogens. When the protein is introduced to immune cells, genes in those cells associated with inflammation turn on, or become expressed, the study showed. These pro-inflammatory genes remain expressed, even when the HIV protein is no longer in the cells. According to the researchers, this “immunologic memory” of the original HIV infection is why people living with HIV are susceptible to prolonged inflammation, putting them at greater risk for developing cardiovascular disease and other comorbidities.

“This research highlights the importance of physicians and patients recognizing that suppressing or even eliminating HIV does not eliminate the risk of these dangerous comorbidities,” Michael Bukrinsky,professor of microbiology, immunology, and tropical medicine at GW’s School of Medicine and Health Science and lead author on the study, said. “Patients and their doctors should still discuss ways to reduce inflammation and researchers should continue pursuing potential therapeutic targets that can reduce inflammation and co-morbidities in HIV-infected patients.”

For the study, the research team isolated human immune cells in vitro and exposed them to the HIV protein Nef. The amount of Nef introduced to the cells is similar to the amount found in about half of HIV-infected people taking antiretrovirals whose HIV load is undetectable. After a period of time, the researchers introduced a bacterial toxin to generate an immune response from the Nef-exposed cells. Compared to cells that were not exposed to the HIV protein, the Nef-exposed cells produced an elevated level of inflammatory proteins, called cytokines. When the team compared the genes of the Nef-exposed cells with the genes of the cells not exposed to Nef, they identified pro-inflammatory genes that were in a ready-to-be-expressed status as a result of the Nef exposure.

According to Bukrinsky, the findings in this study could help explain why certain comorbidities persist following other viral infections, including COVID-19.

“We’ve seen this pro-inflammatory immunologic memory reported with other pathogenic agents and often referred to as ‘trained immunity,'” Bukrinsky explains. “While this ‘trained immunity’ evolved as a beneficial immune process to protect against new infections, in certain cases it may lead to pathological outcomes. The ultimate effect depends on the length of this memory, and extended memory may underlie long-lived inflammatory conditions like we see in HIV infection or long COVID.”

Source: George Washington University

Categories : General Interest Healthcare Politics and RegulationsTags :

Healthcare Workers Strike over Salaries and Poor Working Conditions

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On Tuesday 22 November, healthcare workers were among the public sector employees who engaged in a strike action to protest a lack of pay increase. A number of hospitals and clinics across South Africa and particularly Gauteng were affected, the Daily Maverick reports.

Unions had been offered a 3% increase plus an additional R1000, which the negotiating unions refused. Union leaders rejected this, demanding a 10% increase. Inflation is running at 6%, and food prices have risen by 12% from the start of the year to September – largely driven up by the war in Ukraine.

Union leaders say the strikes and protests are driven by wages staying the same over the past few years. Healthcare workers had already been suffering high rates of burnout battling COVID waves. In addition, workers complained of being understaffed, and enduring dire working conditions from lack of equipment, medication and food.

On Tuesday morning, burning tires were placed on Chris Hani Road in Soweto. Striking workers wearing union colours were preventing many vehicles, including ambulances, from entering Chris Hani Baragwanath Hospital. Patients inside were being left unattended.

Sebokeng Hospital in Sedibeng meanwhile was running on a skeleton staff, with doctors and nurses prevented from entering. Emergency services were being diverted to nearby facilities.

Meanwhile, GroundUp reported that patients were being turned away from Mabandla Clinic in the Eastern Cape. In Gqeberha, Motherwell NU8 clinic and the Motherwell Healthcare Centre were both reported to be closed. 

On Tuesday afternoon, the Gauteng Department of Health received an interdict against the strikes, preventing striking workers from interfering with access to hospitals, EWN reports. The public healthcare systems in Gauteng and other provinces have already been strained, with recent high-profile protests and resignations over inadequate funding and allegations of corruption.