Tag: 27/10/21

Large Study Finds Statins Ineffective, Possibly Worsen COVID

Source: Unsplash

Though small studies have suggested that statins, which lower low-density lipoprotein (LDL), may also reduce COVID severity or mortality, findings from a large study suggest that it has no effect and may even worsen the disease.

In the effort to fight COVID, researchers have attempted to find existing medications that might have an effect on the outcome of the disease, and statins were one readily available candidate that appeared to have some effect. However, a new study published in the journal PLOS ONE suggests they may not be suitable.

“Despite the apparent beneficial effect of statins on the outcomes of various infectious diseases, our study revealed that their specific use to treat COVID is probably not merited,” said senior study author Petros Karakousis, MD, professor of medicine at the Johns Hopkins University School of Medicine. “Compared with earlier research, we looked at a larger and more widely varied inpatient population, and had better criteria for defining disease severity, thereby enabling our results to be more relevant for predicting the impact of statins on COVID outcomes in hospitalised patients.”

In the study, researchers reviewed the records of 4447 hospitalised patients, ages 18 years or older, who had been diagnosed with SARS-CoV-2 infection between March 1 and June 30, 2020. Of these, 594 (13%) were receiving statins at admission, with most statin users being men (57%) and older (ages 52–78 compared with ages 29–62) than the non-statin users. The highest percentage of statin users were black (47%), had hypertension (74%) or diabetes (53%), and were more likely to take medications for lowering blood pressure – along with statins to reduce their LDL cholesterol.

After accounting for confounding factors, statin use was found to have no significant effect on COVID mortality. However, they did find that patients hospitalised with COVID and taking statins had an 18% increased risk for having a more severe form of the disease.

“One plausible explanation for this finding is that statins increase cellular production of angiotensin-converting enzyme 2 [ACE2], the receptor on a cell’s surface through which SARS-CoV-2 gains entry,” said Prof Karakousis. “Therefore, statins may lower a cell’s resistance to infection and in turn, increase the odds that the patient will have a more severe case of COVID.”

Prof Karakousis said future studies should attempt to better define the relationship between statin use and COVID, noting that all previous ones were retrospective and had factors that could not be eliminated, such as many statin users being overweight.

The only way to definitively determine if statins have any benefit for patients with COVID is to conduct a randomised, placebo-controlled clinical trial.

Source: Johns Hopkins Medicine

Nut Consumption Linked to Long-term Breast Cancer Survival

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In a study of breast cancer survivors, the consumption of nuts was linked with reduced risks of breast cancer recurrence or death.

Researchers examined data for 3449 breast cancer survivors from the Shanghai Breast Cancer Survival Study who completed a dietary assessment five years after diagnosis. Of the participants, there were 374 deaths during a median follow-up of 8.27 years after the dietary assessment. Among 3274 survivors who did not have a previous recurrence at the time of their dietary assessment, 209 developed breast cancer-specific events, including recurrence, metastasis, or breast cancer mortality.

There was a dose-response pattern in the relationship between nut consumption and risk of breast cancer recurrence or death, with those consuming the highest amounts having the lowest risks. Also, the association was stronger for survivors who had earlier stages of breast cancer than for those who had later stages.

The findings were published in the International Journal of Cancer.

Source: Wiley

In Metastatic Colon Cancer, Youth is no Advantage

Colon cancer cells. Source: National Cancer Institute on Unsplash

Even though young patients with metastatic colorectal cancer tend to be more fit and receive more intensive treatment than older patients, both groups survive for roughly the same amount of time, according to a new study by Dana-Farber Cancer Institute investigators.

The findings, published in the Journal of the National Cancer Institute, come as colorectal cancer rates in young people are rising. The researchers said the results are somewhat surprising, as younger patients, who usually have fewer complicating health factors, might be expected to survive longer than older patients.

“As a group, younger patients are more physically active and have higher performance status and are better able to perform the activities of daily living than older patients. They also tend to be treated with higher doses of therapy and have less severe side effects,” said study senior author Kimmie Ng, MD, MPH, director of the Young-Onset Colorectal Cancer Center at Dana-Farber. “This is the first study to compare survival in younger versus older patients participating in a clinical trial of treatment for metastatic colorectal cancer.”

The study drew on clinical trial data which tested a combination of chemotherapy and biologic therapy in patients with metastatic colorectal cancer, comparing patients under 50 with those over 50.

“We found no significant difference in overall survival between the two groups,” said Dana-Farber’s Marla Lipsyc-Sharf, MD, the first author of the study. The median survival for patients with young-onset colorectal cancer was 27.07 months vs. 26.12 months for the older-onset group. Progression-free survival – how long patients lived before the cancer worsened – was also similar for the two groups: 10.87 months for the younger patients vs. 10.55 for the older ones.

Confounding expectations even further, patients under age 35 had the shortest median overall survival of any age group: 21.95 months vs 26.12 months in older-onset patients. Because the study included relatively few patients younger than 35, the difference is not considered statistically significant, researchers noted, but it aligns with previous research suggesting that very young patients have worse outcomes.

Cases are markedly on the rise: between 2000 and 2013, incidence of the disease in people under age 50 increased approximately 22%, even as overall incidence of colorectal cancer has declined. Yet despite a wellspring of new research, no definitive cause for the increase has been found.

“If current trends hold, colorectal cancer is projected to be the second leading cancer and leading cause of cancer death in patients ages 20–49 by the year 2040,” Lipsyc-Sharf stated. “It is important to understand survival in this population in order to develop tailored treatments.”

That younger patients fare no better than older ones despite more favourable factors could suggest that colorectal cancer is more aggressive at an earlier age. But there is no conclusive evidence that that is the case.

“Research has yet to identify consistent molecular differences in the colorectal cancer cells of younger patients and older patients,” Dr Lipsyc-Sharf noted. Current studies also are exploring whether differences in the intestinal microbiome of younger and older patients might explain the increased incidence of early-onset colorectal cancer.

Source: Dana Farber Cancer Institute

COVID Test Sensitivity Changes with Circadian Rhythm

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A new study suggests that the sensitivity of tests for SARS-CoV-2 vary throughout the day according to the body’s circadian rhythm, which could have implications for how the disease is managed.

Carl Johnson, Cornelius Vanderbilt Professor of Biological Sciences, wondered how the virus might act differently depending on the time of day and the body’s circadian rhythms, and collaborated with colleagues to determine if the percentage of people testing positive for COVID varies based on time of day. They found that people were up to two times as likely to have an accurate positive test result if they tested in the middle of the day compared to at night. Their findings were published in the Journal of Biological Rhythms.

The data support the hypothesis that COVID acts differently in the body based on our natural circadian rhythm, which has also been implied by studies of other viral and bacterial infections. COVID virus shedding, when infected cells release infectious virus particles into the blood and mucus, appears to be more active around midday due to modulation of the immune system by our biological clock.

“Taking a COVID test at the optimal time of day improves test sensitivity and will help us to be accurate in diagnosing people who may be infected but asymptomatic,” Prof Johnson said. Their results indicate that viral load is lower after 8 pm. If people choose to get tested at that time, there could be a higher chance of a false-negative result. False negatives can be harmful to the community and for the patient, who might not seek additional care due to their negative test result.

A difference in COVID viral shedding throughout the day would help inform treatment for the disease. As Johnson and his co-authors report, the peak shedding in the afternoon, when patients are more likely to interact with others or seek medical care, could play a role in increasing the spread of the virus in hospitals and the wider community.

Further research is needed to confirm the diurnal nature of SARS-CoV-2. Experimentally testing COVID patients to see if individuals shed the virus differently throughout the day would have important public health implications, Prof Johnson said.

Source: Vanderbilt University

Vaccine to Prevent Hookworm Infection Could be a ‘Gamechanger’

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There’s been a significant breakthrough in the development of a vaccine to prevent hookworm infection – a parasite which causes serious disease in tens of millions of people globally.

Mouse trials of the vaccine candidate in mice indicate that it is more than twice as effective than current alternatives. The results were published in Vaccines.

Professor Istvan Toth from UQ’s School of Chemistry and Molecular Biology said the easy oral administration would be a gamechanger for developing countries.

“Our vaccine candidate can be orally self-administered, bypassing the need for trained medical staff, and means there’s no requirement for special storage, enabling it to reach large, isolated populations,” Professor Toth said, noting that costs can be significantly reduced.

A serious healthcare challenge
About 500 million people worldwide are infected with hookworm, which lives within the human intestine, feeding on the host’s blood, digested through a special set of enzymes.

It’s often found in regions with poor water quality, sanitation, and hygiene – greatly impacting on the physical and cognitive development of children and increasing the risk of mortality and miscarriage.

UQ’s trials in mice showed significant improvements on an alternative vaccine candidate which only achieved a 30 to 50 per cent reduction in the number of worms.

“The UQ-developed vaccine resulted in an impressive 94% worm reduction in mice,” Professor Toth said, noting that besides being easier to deliver, it “triggers a staggeringly good immune response.”

Hookworms lose their appetite
Paper co-author Dr Mariusz Skwarczynski said the hookworm’s digestion enzyme (APR 1) was the target.

“When the function of these enzymes is blocked, the parasite starves,” Dr Skwarczynski said.

“Our vaccine produces antibodies against the hookworm enzymes responsible for the digestion of blood – they simply stop being able to eat properly.”

The researchers plan to continue working on and refining the vaccine candidate in preclinical development settings, to ensure its safety and efficacy, before beginning human clinical trials.

Source: University of Queensland

A New Mechanism Explains Hair Loss in Men and Women

Bald man
Photo by Brett Sayles on Pexels

Studies of balding male mice have uncovered a possible cause of hair loss in men and women as well. The findings, published in Nature Aging, provide new insight into how hair and tissues age.

The study shows as hair stem cells age, they lose the adhesion that keeps them lodged inside the hair follicle. As their adhesiveness wanes, the stem cells escape from their location, called the bulge, into the dermis. Once outside their delicate microenvironment, they generally can’t survive.

“The result is fewer and fewer stem cells in the hair follicle to produce hair,” said lead author Rui Yi, the Paul E. Steiner Research Professor of Pathology at Northwestern University Feinberg School of Medicine. “This results in thinning hair and ultimately baldness during ageing.”

This finding could be applicable to older men and women with thinning hair as mice and humans share hair and stem cell similarities, Prof Yi said.

By labelling individual stem cells with a fluorescent marker, the researchers were able, for the first time, to track hair follicle ageing in real time in live animals. Scientists also discovered two key genes responsible for enhancing adhesiveness of the stem cells. They are now trying to reinstate these genes to see if that will reverse hair loss.

During follicles’ normal cycles of life and death, a large number of stem cells remain permanently lodged in the stem cell compartment of hair follicles to keep producing hair follicle cells.

“We believe this stem cell escape mechanism has never been reported before, because nobody could track the aging process in live animals,” Yi said.

Though scientists knew hair follicles become miniaturised during aging, how it happened was unclear. Many thought it was due to cell death or the inability of cells to divide as they age.

“We discovered, at least in part, it is due to hair follicle stem cells migrating away from their niche,” Prof Yi said. “Cell death also occurs during our observation. So, our discovery doesn’t dispute existing theories but provides a new mechanism.”

Source: Northwestern University