Month: September 2021

Categories : Cancer Lab Tests and ImagingTags :

New HPV Test Enables Precision Treatment

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Source: NCI on Unsplash

Researchers have made advances in improving detection of the human papillomavirus (HPV) in the bloodstream, which could further hone precision treatment of the illness.

The team sequenced circulating tumour DNA, which can lead to the detection of HPV in a person’s blood. Previous science in the field has proven that the virus, which causes cancers in the throat, mouth, and genital areas, can be found in the bloodstream but tests have had limited sensitivity. The new study enables ‘ultrasensitive’ detection, which could pave the way toward greater use of precision medicine for patients with cancers affecting these vulnerable areas of the body.

In a cohort of patients with advanced cervix cancer, the new sequencing method detected 20-fold lower levels of HPV circulating tumour DNA, making it a promising new method to monitor the disease.

The results come from the laboratory of Senior Scientist Dr Scott Bratman at Princess Margaret Cancer Center and are published in Clinical Cancer Research. “Increasingly, as clinicians we’re focused on precision medicine and making sure we’re not over-treating people while still curing them, that’s a very difficult balance to strike,” Dr Bratman said.

One way is to use liquid biopsy approaches or blood-based biomarkers, such as circulating tumour DNA, in order to monitor how the treatment is progressing, he added.

“We’re really at the cusp of a revolution from a technology, clinical implementation and standard of care standpoint, where five to 10 years from now we will not be treating everybody with the same dose of radiation and chemotherapy, and then waiting months to see if the treatment was effective,” he said. “I’m confident we will be giving much more tailored doses.”

When physicians scale back on these treatments, there is a risk of the cancer reoccurring. With more sensitive tests, reoccurrences can be detected early and patients returned to treatment.

“Patients who need more treatment will then be able to continue on, or different treatments can be added,” Dr Bratman said. “We can spare the vast majority of patients who will not need those interventions and provided them with a greater quality of life once they’re cured of the cancer.”

The work will enable further study in the field, refining the approach using larger study groups, and eventually, practice-changing clinical trials. This technique could also be applied to other cancer-causing viruses such as certain types of stomach cancer and lymphomas.

Source: Princess Margaret Cancer Center

Categories : COVIDTags :

More ACE2 Makes Pancreatic Cells a COVID Target

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Source: CDC

Researchers have revealed insights into how SARS-CoV-2 attacks the insulin-producing cells of the pancreas.

There is mounting evidence of damage to the pancreas and resulting diabetes attributed to COVID, which is of great concern. The virus targets the angiotensin converting enzyme 2 (ACE2) protein on the surface of those cells, and is the subject of a special presentation at this year’s Annual Meeting of the European Association for the Study of Diabetes, given by the University of Siena’s Professor Francesco Dotta. 

“The SARS-CoV-2 virus attacks specific host tissues because of the presence of viral receptors on the surface of the target cells. As such, virus binding to ACE2 protein is the key determinant for its entry, propagation and transmissibility,” explained Prof Dotta.

“Multiple studies have shown that older adults and those with chronic medical conditions like heart and lung disease and/or diabetes are at the highest risk for complications from SARS-CoV-2 infections. Moreover, impaired blood sugar control is associated with increased risk of severe COVID, suggesting a link between COVID infection and diabetes. Several reports indicate a wide, although variable, distribution of the ACE2 protein among different tissues.”

Prof Dotta and colleagues studied the ACE2 expression pattern in pancreatic tissue samples of non-diabetic multiorgan donors to better understand the molecular link between COVID and diabetes.

In the ‘normal’ pancreas, ACE2 is highly expressed in microvasculature and in ductal cells. “Importantly, we found that ACE2 was expressed in human pancreatic islets, where it is preferentially expressed in insulin producing beta-cells. We also demonstrated that ACE2 levels were increased under pro-inflammatory conditions, thus confirming the link between inflammation and ACE2 also in pancreatic islet beta cells.”

In order to isolate the mechanism involved in the upregulation of ACE2 induced by inflammation, ACE2 levels were measured in human pancreatic islets pre-treated with Jak1/2 and TYK2 inhibitors, which block inflammation in beta cells, and then exposed to pro-inflammatory conditions. 

Prof Dotta said: “We showed that these drugs prevent the ACE2 increase induced by inflammation in human pancreatic islets, demonstrating that SARS-CoV-2 receptor ACE2 is regulated through specific molecular pathways and that its increased expression can be prevented.

“We studied the mechanisms of SARS-CoV-2 virus entry into insulin producing beta cells and we discovered that these cells express the SARS-CoV-2 receptor ACE2.” Other authors have independently confirmed such data.

Of note, additional published data confirmed that SARS-CoV-2 can indeed infect pancreatic insulin-producing cells causing their dysfunction or death. Moreover, during inflammation, ACE2 expression increases several times above standard values.

Prof Dotta concluded: “This means that these insulin-producing beta cells could be even more susceptible to viral infection when inflamed. This finding is also important from a clinical standpoint, since keeping inflammatory status under control in patients with COVID may reduce the expression of ACE2 receptor in beta cells with beneficial effects on blood sugar and metabolic control of patients.”

Source: EurekAlert!

Categories : Environmental EffectsTags :

Solar Exposure Guidelines Could be Revised

On By ModernMedia
Photo by Amy Humphries on Unsplash

Previously published solar exposure guidelines for optimal vitamin D synthesis that were based on a study of skin samples may have to be revised. 

A study published in PNAS has tested the optimum ultraviolet radiation (UVR) wavelengths for human skin production of vitamin D in sunlight.

Though UVR from sunlight can cause sunburn and skin cancer, it is the most important source of vitamin D.

Public health advice on sunshine exposure balances its risk and benefit, which is not a simple task because the health outcomes from UVR exposure vary considerably with wavelength within the sun’s UVR spectrum. For example, the sun’s UVR contains less than 5% short wavelength UVB radiation but this is responsible for over 80% of the sunburn response. Each health outcome from solar exposure has its own unique wavelength dependency.

The link between specific UVB wavelengths and vitamin D production was determined more than thirty years ago in ex vivo skin samples. However, the finding is less well established, with doubts on its accuracy which compromise risk/benefit calculations for optimal solar exposure.

Researchers led by the Professor Antony Young from King’s College London measured blood vitamin D levels in 75 healthy young volunteers, before, during, and after partial or full body exposure to five different artificial UVR sources with different amounts of UVB radiation, to gauge the trade-off between solar exposure benefits, which include vitamin D synthesis, versus the risks of sunburn and skin cancer.

The results were compared against predictions from the old ex vivo vitamin D study, finding that it was not an accurate predictor of benefit from UVR exposure.

The authors’ recommendation is a systematic correction of the ex vivo wavelength dependency for vitamin D. The new study means that many risk benefit calculations for solar UVR exposure must be reviewed with a revised version of the wavelength dependency for vitamin D.

“Our study shows that risk versus benefit calculations from solar exposure may need to be re-evaluated. The results from the study are timely because the global technical committee, Commission internationale de l’éclairage, that sets UVR standards will be able to discuss the findings of this paper to re-evaluate the wavelength dependency of vitamin D. Further research from our group will determine the risk/benefit calculations.”

Professor Antony Young, King’s College London

Source: King’s College London

Categories : CancerTags :

SSRI Antidepressants Could be Used To Fight Cancer

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Natural killer (NK) cells target a cancel cell for destruction. Credit: NCI

Long used to treat depression, selective serotonin reuptake inhibitors (SSRIs) could help improve modern cancer treatments.

In mouse experiments, they slowed the growth of pancreatic and colon cancers, and when combined with immunotherapy, they even halted cancer growth long-term. In some cases the tumours disappeared completely. The researchers’ findings will now be tested in human clinical trials.

The neurotransmitter serotonin, known as the happiness molecule, has many other functions and is mostly found outside the brain, stored in blood platelets. Serotonin reuptake inhibitors (SSRIs), which are used to treat depression, increase serotonin levels in the brain but reduce serotonin in platelets.

Serotonin was already known to be involved  in carcinogenesis. Until now, however, the underlying mechanisms had remained obscure. Now, researchers at the University of Zurich (UZH) and University Hospital Zurich (USZ) have shown that SSRIs or other drugs that lower peripheral serotonin levels can also slow cancer growth in mice.

Pierre-Alain Clavien, Director, Department of Surgery and Transplantation, University of Zurich, said: “Drugs that are already approved for clinical use as antidepressants could help improve treatment of hitherto incurable pancreatic and colorectal cancers.”

Although recent years have seen new, effective treatments such as targeted antibodies or immunotherapies, most patients with advanced-stage abdominal tumours such as colon or pancreatic cancer die within a few years of diagnosis. Tumour cells eventually become resistant to the drugs and are no longer recognised by the immune system. Now, the researchers have discovered the role serotonin plays in this tumour cell resistance mechanism.

Cancer cells use serotonin to boost production of an immunoinhibitory molecule, PD-L1, which binds to killer T cells, rendering them dysfunctional. The cancer cells thus escape destruction by the immune system. In mouse models, the researchers were able to show that SSRIs or peripheral serotonin synthesis inhibitors prevent this mechanism. “This class of antidepressants and other serotonin blockers cause immune cells to recognise and efficiently eliminate tumor cells again. This slowed the growth of colon and pancreatic cancers in the mice,” Clavien said.
PD-L1, via which serotonin exerts its effect, is also the target of modern immunotherapies, also called immune checkpoint inhibitors. The researchers then tested a dual treatment approach in mice: immunotherapy, which increases the activity of killer T cells, was combined with drugs that reduce peripheral serotonin. Cancer growth was suppressed in the animal models in the long term, and in some mice, the tumours disappeared completely.

“Our results provide hope for cancer patients, as the drugs used are already approved for clinical use. Testing such drug combinations on cancer patients in clinical trials can be fast-forwarded due to the known safety and efficacy of the drugs,” said Clavien.

Source: University of Zurich

Categories : Cardiovascular DiseaseTags :

Home BP Monitoring Gets the Thumbs-up From Patients

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BP cuff for home monitoring, Source: Pixabay

Adults needing to track their blood pressure regularly for a hypertension diagnosis preferred home monitoring blood pressure versus at a clinic, kiosk or with a 24-hour wearable device, according to preliminary research presented at the American Heart Association’s Hypertension Scientific Sessions 2021.

According to the American Heart Association, about half of US adults have hypertension, and of those with high blood pressure (BP) over a third are unaware they have it. H

“Most hypertension is diagnosed and treated based on blood pressure measurements taken in a doctor’s office, even though the U.S. Preventive Services Task Force and the American Heart Association recommend that blood pressure measurements be taken outside of the clinical setting to confirm the diagnosis before starting treatment,” said lead study author Beverly Green, MD, MPH, senior investigator and family physician at Kaiser Permanente Washington Health Research Institute. “It is the standard that blood pressure monitoring should be done either using home blood pressure monitoring or 24-hour ambulatory blood pressure monitoring prior to diagnosing hypertension.”

The “gold standard” for out-of-office measurement to determine a diagnosis of high blood pressure is 24-hour ambulatory blood pressure monitoring devices, worn day and night to take continuous blood pressure readings. Measuring BP on a home device with a normal BP cuff, can be more convenient.

The researchers studied adherence and acceptability of different blood pressure measuring methods among 510 adults with elevated BP but without a hypertension diagnosis. Participants in the study were an average age of 59 years old; half were male; the average BP was 150/88 mm Hg and were taking blood pressure-lowering medications.

Participants were randomised to either clinic measurements, home monitoring or kiosk blood pressure monitoring.

Those in the group for clinic measurements were asked to return to the clinic for at least one additional blood pressure check, as is routine in diagnosing hypertension in clinical practice. The home group received home blood pressure machines and the training to use them, and were asked to measure their blood pressure twice in a row, two times daily, for five days, for a total of 20 measurements. The kiosk group was asked to take their blood pressure at a kiosk in their clinic or at a nearby pharmacy three times each on three separate days, for a total of nine measurements. All participants were asked to complete their group-assigned diagnostic regimens within three weeks, and then to complete 24-hour ambulatory blood pressure monitoring. Researchers compared adherence to and the acceptability among each diagnostic method.

They measured adherence to monitoring by noting the percent of individuals in each group who completed their assigned measurement method as instructed. They measured acceptability with questionnaires.

Researchers found that overall acceptability was highest for the at-home group, followed by the clinic and kiosk groups, while 24-hour ambulatory blood pressure monitoring was the least popular. Adherence to the monitoring regimen was lowest in the kiosk group, but more than 90% in the home testing group; more than 87% in the clinic group; nearly 68% in the kiosk group; and 91% for 24-hour ambulatory monitoring among all participants.

“Home blood pressure monitoring was the most preferred option because it was convenient, easy to do, did not disturb their daily personal or work routine as much, and was perceived as accurate,” said Dr Green. “Participants reported that ambulatory blood pressure monitoring disturbed daily and work activities, disrupted sleep and was uncomfortable.”

When asked which diagnostic testing regimen they would prefer, more than half chose home blood pressure monitoring, especially if they were assigned to the home group, where almost 80% preferred home monitoring.

Dr Green suggests that clinicians routinely offer home blood pressure monitoring to their patients with elevated blood pressure.
“Health care professionals should work toward relying less on in-clinic visits to diagnose hypertension and supporting their patients in taking their blood pressure measurements at home,” Dr Green said. “Home blood pressure monitoring is empowering and improves our ability to identify and treat hypertension, and to prevent strokes, heart attacks, heart failure and cardiovascular death.”

Source: American Heart Association

Categories : COVIDTags : 1 Comment

Two Ivermectin Deaths Reported in US State

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Source: Unsplash

Two deaths in the US state of New Mexico have been linked to misuse of ivermectin, the anti-parasitic medicine that has repeatedly been used by people as an anti-COVID medication.

The patients were among 14 in the state who had been hospitalised after being poisoned by the use of ivermectin, which has been widely promoted.

Dr David Scrase, the acting head of the state health department, said the two patients who died (38 and 79 years old) had both contracted the coronavirus and attempted to treat it themselves with ivermectin, leading to kidney failure in one patient.

“It’s the wrong medicine for something really serious,” Dr Scrase said.

The American Association of Poison Control Centers reported 1440 cases of ivermectin poisoning up to 20 September, more than three times seen in the same period in 2019 and 2020. A majority of this year’s reports came over the past few months as people sought prescriptions after false claims about the drug’s effectiveness in COVID patients started to circulate on social media, podcasts and talk radio. Many other states are seeing increasing cases of ivermectin poisoning.

Dr Susan Smolinske, the director of the New Mexico Poison and Drug Information Center, said that about half of the reported cases of ivermectin poisoning this year were people who took the drug to prevent COVID.

While certain versions of ivermectin are prescribed to humans to treat head lice and other parasites, other more concentrated formulations are commonly used in the equine and livestock industries to combat worms and parasites.

Previously, Dr Smolinske said, many of the incidents in New Mexico involved children mistakenly taking chewable tablets intended for dogs, however the poison centres had recently seen more instances of people taking concentrated forms of the drug intended for large animals, which may contain other ingredients not intended for human use.

“Most of our cases are of the horse or dewormer or pour-on product, so they’re highly concentrated compared to those tablets for dogs,” said Dr Susan Smolinske, the director of the New Mexico Poison and Drug Information Center.

Dr Smolinske said misuse of the drug can cause drowsiness, dizziness, tremors or even a coma. “It gets into the brain, and if you take a high enough dose, it has difficulty getting out of the brain,” she said.

Source: New York Times

Categories : CancerTags :

Oxford-AstraZeneca Vaccine Tech Tapped to Treat Cancer

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Source: National Cancer Institute on Unsplash

The Oxford-AstraZeneca vaccine’s success against SARS-CoV-2 has prompted scientists to develop a vaccine for cancer, using Oxford’s viral vector vaccine technology.

When tested in mouse tumour models, the two-dose therapeutic cancer vaccine increased the numbers of anti-tumour T cells infiltrating the tumours and improved the efficacy of cancer immunotherapy. Compared to immunotherapy alone, combination with the vaccine resulted in a greater reduction in tumour size and improved survival.

The study, which was done by Professor Benoit Van den Eynde’s group at the Ludwig Institute for Cancer Research, University of Oxford in collaboration with co-authors Professor Adrian Hill and Dr Irina Redchenko at the University’s Jenner Institute, has been published in the Journal for ImmunoTherapy of Cancer.

Cancer immunotherapy has improved outcomes for some cancer patients. Anti-PD-1 immunotherapy works by unleashing anti-tumour T cells to allow them to kill cancer cells. However, in the majority of cancer patients, anti-PD-1 therapy is still ineffective .

One reason for the poor efficacy of anti-PD-1 cancer therapy is that some patients have low levels of anti-tumour T cells. Oxford’s vaccine technology generates strong CD8+ T cell responses, which are necessary for strong anti-tumour effects.

The team developed a two-dose therapeutic cancer vaccine with different prime and boost viral vectors, one of which is the same as the vector in the Oxford-AstraZeneca COVID vaccine. In order to create a vaccine treatment that specifically targets cancer cells, the vaccine was designed to target two MAGE-type proteins found on the surface of many types of cancer cells.

Preclinical experiments in mouse tumour models demonstrated that the cancer vaccine increased the levels of tumour-infiltrating CD8+ T cells and enhanced the response to anti-PD-1 immunotherapy. The combined vaccine and anti-PD-1 treatment resulted in a greater reduction in tumour size and improved the survival of the mice compared to anti-PD-1 therapy alone.

Benoit Van den Eynde, Professor of Tumour Immunology at the University of Oxford, said: “We knew from our previous research that MAGE-type proteins act like red flags on the surface of cancer cells to attract immune cells that destroy tumours.

“MAGE proteins have an advantage over other cancer antigens as vaccine targets since they are present on a wide range of tumour types. This broadens the potential benefit of this approach to people with many different types of cancer.

“Importantly for target specificity, MAGE-type antigens are not present on the surface of normal tissues, which reduces the risk of side-effects caused by the immune system attacking healthy cells.”

Human trials in 80 patients with non-small cell lung cancer will be launched later this year.

Adrian Hill, Lakshmi Mittal and Family Professorship of Vaccinology and Director of the Jenner Institute, University of Oxford, said: “This new vaccine platform has the potential to revolutionise cancer treatment. The forthcoming trial in non-small cell lung cancer follows a Phase 2a trial of a similar cancer vaccine in prostate cancer undertaken by the University of Oxford that is showing promising results.

“Our cancer vaccines elicit strong CD8+ T cell responses that infiltrate tumours and show great potential in enhancing the efficacy of immune checkpoint blockade therapy and improving outcomes for patients with cancer.”

Source: Oxford University

Categories : Ethics and Law General InterestTags :

Health Dept Suspends DG Buthelezi over Digital Vibes Tender

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Photo by Tingey Injury Law Firm on Unsplash

In the latest development of the R150 million Digital Vibes tender fallout, Health department director-general Dr Sandile Buthelezi has been placed on precautionary suspension 

On Sunday, health ministry spokesperson Foster Mohale  confirmed Buthelezi’s suspension following a Special Investigating Unit (SIU) report into the alleged tender fraud. Deputy DG Dr Nicolas Crisp will take over as acting DG until the completion of Buthelezi’s hearing process. Buthelezi had previously been on leave.

Mohale said that while the R150m Digital Vibes communications contract was already secured when Buthelezi assumed the DG role, it was his inaction in his role as heady of accounting authority regarding the contract that led to the suspension, said Mohale. 

The tender process was rife with irregularities, involving fictitious companies and doctoring scores of bidding companies.

“The procurement process was … a sham, designed and conducted to reach the predetermined result that Digital Vibes would be appointed,” lead investigator Rajendra Chunilall said in the SIU’s founding affidavit.

Former health director-general Precious Matsoso told the SIU that Tahera Mather, a friend of Dr Mkhize’s and a beneficial owner of Digital Vibes, began work at the department straight after Dr Mkhize’s appointment as minister. Matsotso had been pressured by Dr Mkhize to ensure that Mather was hired. Instead of a public tender for the National Health Insurance (NHI) communications contract as advised by the Treasury, it was issued as a closed tender to ten companies.

Two of these companies did not exist and six of which, including a computer equipment supplier and a graphic design company, did not respond as the tender was out of their scope, according to forensic accountant Hesti le Roux’s investigation.

Mather is also alleged to have created a fraudulent profile for Digital Vibes with the relevant skills and experience, including a fake team some of whom never worked for Digital Vibes and were not paid. 

Due to this rigging, only Digital Vibes and Brandswell responded; the latter had the upper hand as its R69m quote was far cheaper than Digital Vibes’ R141m,

However, the department then inexplicably issued a second RFP, amending the requirements.

Brandswell was “irregularly and irrationally” marked down by the department’s five-member tender evaluation committee (TEC), which included deputy director-general Anban Pillay and head of communications Popo Maja. This was despite Brandswell being a “long-standing and reputable communication solution service provider”, Le Roux said.

“Clearly, the recommendation by the TEC to award the contract to Digital Vibes was invalid in terms of the provisions [of] the constitution, because the procurement process was not fair, equitable, transparent, competitive and/or cost-effective. Therefore, the service level agreement that was concluded with Digital Vibes should be declared invalid,” Le Roux concluded.

Source: Times Live

Categories : PaediatricsTags :

Managing Children Who Swallowed Button Batteries

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Photo by Anna Shvets on Pexels

Small, flat ‘button’ batteries are commonly used in many electronic devices, and increasing numbers of children are ingesting button batteries, US data shows. A practice article in the CMAJ’s (Canadian Medical Association Journal) “Five things to Know About…” series highlights some key points for managing button battery ingestion.

  • Injuries from battery ingestion are increasing according to US data. Between 1999 and 2019, the United States National Poison Data System reported a 66.7% increase in yearly ingestion of button batteries and a 10-fold increase in complications.
  • Battery size and type influence complications. Lithium batteries and those 20 mm or larger are more dangerous and can become lodged in the oesophagus, especially in children under six years of age.
  • Urgency of management depends on the location of the battery. Batteries in the oesophagus should be removed immediately by a health care provider to prevent tissue erosion. Urgent removal in a health care setting is advised in children under five years who swallow batteries 20 mm or larger. Otherwise, children should be monitored as outpatients to see if they pass the battery.
  • Honey or sucralfate should be administered after battery ingestion. Honey given to children older than one year by their caregiver (10mL every 10 minutes, up to six doses) before arrival to the hospital and sucralfate administered in hospitals can reduce tissue damage due to swallowed button batteries.
  • Monitor children for long-term complications. Serious complications can occur despite removal of the battery. Caregivers should monitor for symptoms, including gastrointestinal bleeding and vomiting, weeks to months after removal.

Source: Medical Xpress

Categories : Obstetrics & GynaecologyTags :

Consensus Statement Cautions on Paracetamol Use in Pregnancy

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Source: Anna Hecker on Unsplash

A consensus statement by 13 doctors in different countries suggests that pregnant people only take paracetamol/acetaminophen if it is medically necessary, Their paper, published in the journal Nature Reviews Endocrinology, the group paracetamol/acetaminophen (APAP). 

In the same journal issue, an accompanying Editorial outlines the consensus statement and noting that its authors are not calling for a ban on the drug being used, instead they are suggesting that it be taken more cautiously by pregnant women because of a possible risk of birth defects.

Research in recent years has shown that it is possible under some circumstances for APAP to alter foetal development which can herald problems with neurological, urological and reproductive disorders in the baby – the authors found evidence of birth defects in 26 out of 29 studies. The authors call for more research into the possible problems with the drug’s use by pregnant women. They also acknowledge – as do several experts in a reaction piece published on the Science Media Centre site – that APAP is the only pain management drug available for pregnant women. And they point out that medical use of APAP is generally warranted when the mother experiences problems that can negatively impact her baby –  such as having a fever. But they also note that pregnant women’s APAP use appears to have crept up into general use as it has gained a reputation as being safe to use as an all-purpose painkiller.

The expert group and the authors of the new paper notably both point out that the recommendation does not differ from that already in use by most OB/GYNs – and similar wording generally appears on bottles of products based on APAP, such as Tylenol.

The consensus statement’s authors say their intention behind the article is to bring renewed and more focused attention to the possibility of APAP use leading to certain birth defects and the conditions under which they might arise. They note that current research has shown, for example, that the risk of harm seems to rise as the duration of APAP use goes up. In light of this, they suggest pregnant women consider using the drug for short term pain management, rather than as a long-term solution.

Source: Medical Xpress