MIS-C is a rare condition that usually affects school-age children who initially had only mild COVID symptoms or no symptoms at all. The researchers also found that IVIG works in a similar manner for treating Kawasaki disease, another rare inflammatory condition that affects children and shares symptoms with MIS-C.
MIS-C is marked by severe inflammation of two or more parts of the body, including the heart, lungs, kidneys, brain, skin, eyes and gastrointestinal organs. Its symptoms overlap with Kawasaki disease, and treatments for MIS-C are partly guided by what is known about the treatment of Kawasaki disease. IVIG, which is made up of antibodies purified from blood products, is a common and effective treatment for heart complications caused by Kawasaki disease. For MIS-C patients, however, IVIG alone does not always resolve symptoms, and healthcare providers may need to prescribe additional anti-inflammatory drugs.
In order to better understand how IVIG works and to improve treatments for children with MIS-C, researchers profiled immune cells from patients with MIS-C or Kawasaki disease. The team sampled cells before treatment began as well as 2 to 6 weeks after patients received IVIG, and found that neutrophils from these patients were highly activated and a major source of interleukin 1 beta (IL-1β), a driver of inflammation. After IVIG treatment, these activated neutrophils were significantly depleted in patients with MIS-C or Kawasaki disease.
The study authors believe their findings are the first to explain why IVIG is effective for both conditions. More work is needed however to understand how IVIG causes cell death in these activated neutrophils and why certain patients with MIS-C require additional anti-inflammatory treatments.
A review of studies has found an association with the use of antihypertensive medications and the development of psoriasis.
Psoriasis is a chronic inflammatory skin disease that, when inflicted, can be detrimental to the individual’s overall quality of life. The prevalence rate of psoriasis is 0.1–11%, more common in Caucasian and Scandinavian populations, and also more common in older people and in high-income countries as well.
In the analysis, which is published in the British Journal of Clinical Pharmacology, data from 13 studies indicated that angiotensin-converting-enzyme inhibitors, beta- blockers, calcium-channel blockers, and thiazide diuretics may increase the risk of psoriasis. However, there was no greater increase of any of the drugs relative to the others.
The authors of the analysis propose several mechanisms by which blood pressure medications may affect an individual’s risk of developing skin conditions.
“Our findings indicate that patients who take antihypertensive drugs should be carefully monitored for psoriasis,” said senior author Hye Sun Gwak, PharmD, PhD, of Ewha Womans University, in Seoul.
A study published in Nature Microbiology has for the first time provided compelling evidence of connections between antimicrobial-resistant bacteria causing surgical-site infections and insects and other arthropods. Among these bacteria are those with resistance to drug-of-last-resort.
Antimicrobial resistance (AMR) could render many of the current mainstay and last-resort antibiotics useless, resulting in many more deaths from previously treatable infections. A UN report estimated in 2019 that AMR could lead to ten million deaths per year, and cost the world $100 trillion, by 2050.
“Similar to our experience over the last eighteen months with the pandemic, a problem currently seen from afar will quickly come into focus much closer to home” said Professor Tim Walsh at Oxford University
The report found that:
About 20% of the flies, cockroaches, spiders, moths, and ants were carrying carbapenem resistance.
Of these, 70-80% were carrying extended spectrum cephalosporin resistance, that is, enzymes that confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam.
Currently there are about 18 million flies to every human, but conservative global warming projections estimate insect and fly population will double if temperatures increase by 1.5 degrees.
By 2080 there could be around 50 000 trillion flies carrying carbapenem resistance and spreading AMR across the planet.
“Similar to our experience over the last eighteen months with the pandemic, a problem currently seen from afar will quickly come into focus much closer to home,” said Prof Walsh. “The clinical burden of AMR is most felt in low-middle income countries, but the increase in global temperatures, due to climate change, will result in a significant increase in flies and many other insects and a subsequent increase in the global velocity of antibiotic resistance.” Prof. Tim Walsh, Oxford University.
AMR is a pervasive issue, stretching from hospitals to farming and human waste processing. Resistance can spread within hospitals, communities, farms, and wastewater systems, and domestic animals can share AMR microorganisms with humans.
One tactic is to repurpose previously developed drugs that did not work for humans and use these for animals, buying time for us to develop new drugs.
Another is to rethink hospital prevention and infection control measures, especially in lower- and middle-income countries. Further research into how arthropods disseminate AMR and improving healthcare infrastructure to reduce the spread of AMR by arthropods.
“Most antibiotics currently used on animals are also the same that are used in humans, creating a pool where bacteria can evolve to evade drugs and then reinfect humans,” said Prof Tim Walsh of Oxford University.
“There is no silver bullet when it comes to tackling the worldwide threat of AMR,” he added. “The Ineos Oxford Institute for AMR Research is committed to finding non-human antibiotic therapies and feeds for animals, addressing the increase in AMR in human infections and raising awareness of this hidden threat to human health. But this is a global medical crisis that ultimately will only be resolved with a global response.”
A new study has revealed that the presence of Clostridium difficile is widespread in non-healthcare settings around the world. This research from the University of Houston was present at Infectious Disease Society of America IDWeek.
Clostridium difficile, or C diff, is a gram-positive bacterium that causes inflammation of the colon and is the most implicated in antibiotic-associated diarrhoea. The organism is commonly found in water, air, human and animal faeces, hospital surfaces, and soil. Responsible for for almost half a million infections and 15 000 deaths in the US each year, the presence of C diff in community settings has been mostly overlooked. Over 2014 to 2017, researchers gathered samples from public areas, health care settings, and shoe soles in the US and 11 other countries. They compared the rates of C diff positivity between settings, including shoe soles, which were investigated for their potential role in environmental transmission.
In samples taken from around the world, 26% of environmental samples from health care and non-health care sites tested positive for C diff strains. Shoe soles had the highest positivity rates, with 45% of samples testing positive for the bacteria.
“C diff infection was known historically as a hospital-associated infection, and efforts to reduce the infection and control its spread have been focused on hospitals and long-term care facilities,” said presenting author Jinhee Jo, a postdoctoral infectious disease fellow at the University of Houston. “Recently, cases of community-acquired C diff have been increasing, which suggests the need for broader community stewardship.”
“The results of this study shift our understanding of C diff, including where it is found, how it is transmitted, and who it affects,” said Kevin W. Garey, professor of pharmacy practice at the UH College of Pharmacy. “We can no longer think of C diff as only existing in health care settings, and the population at risk is no longer just the very sick patient in the hospital. Identifying that person at risk anywhere in the world should become a priority regardless of whether the person is in a hospital or the community.”
A previously unknown virus that can infect humans and cause disease has been identified by scientists in Japan. The novel infectious virus, named Yezo virus and transmitted by tick bites, causes a disease characterised by fever and a drop in blood platelets and leucocytes. The discovery was reported in Nature Communications.
Keita Matsuno, a virologist at Hokkaido University’s International Institute for Zoonosis Control, said: “At least seven people have been infected with this new virus in Japan since 2014, but, so far, no deaths have been confirmed.”
The Yezo virus was discovered in 2019 after a 41-year-old man was hospitalised with fever and leg pain after a possible tick bite while walking in a local forest. He was treated and discharged after two weeks, but tests showed he had not been infected with any known viruses carried by ticks in the region. A second patient showed up with similar symptoms after a tick bite the following year.
Genetic analysis of viruses isolated from blood samples of the two patients found a new type of orthonairovirus, a class of nairoviruses. This class includes pathogens such as the Crimean-Congo haemorrhagic fever virus. The scientists named it Yezo virus, after an old name for Hokkaido, the northern Japanese island where the pathogen was discovered. The new virus was found to be closely related to Sulina virus and Tamdy virus, detected in Romania and Uzbekistan, respectively, and recently Tamdy virus reportedly caused acute fever in humans in China.
The researchers then analysed blood samples taken from hospital patients who showed similar symptoms after tick bites since 2014, finding additional positive samples from five patients. These patients, including the first two, had a fever and reduced blood platelets and leucocytes, and showed indicators of abnormal liver function.
To determine the likely source of the virus, the research team screened samples collected from wild animals in the area between 2010 and 2020. They found antibodies for the virus in deer and raccoons and the virus RNA was also found in three major species of ticks in Hokkaido. Matsuno noted that, “The Yezo virus seems to have established its distribution in Hokkaido, and it is highly likely that the virus causes the illness when it is transmitted to humans from animals via ticks.”
As the COVID pandemic has shown, many unknown viruses are present in animal and some can jump to humans. “All of the cases of Yezo virus infection we know of so far did not turn into fatalities, but it’s very likely that the disease is found beyond Hokkaido, so we need to urgently investigate its spread,” said Matsuno.
The research team now plans to determine the distribution of the virus nationwide.
Patients with psoriasis have often reported that glycerine, common in many skin lotions, is effective at combatting their psoriasis and there is now objective evidence to support their reports.
Researchers found that whether applied topically or ingested in drinking water, glycerine, or glycerol, helps calm the classic scaly, red, raised and itchy patches in their psoriasis model, Dr. Wendy Bollag, cell physiologist and skin researcher at the Medical College of Georgia and Charlie Norwood VA Medical Center and her colleagues report in the International Journal of Molecular Sciences.
The studies also provide more evidence of the different ways glycerine enables the healthy maturation of skin cells through four stages that result in a smooth, protective skin layer. Psoriasis is an immune-mediated problem that typically surfaces in young adults in which skin cells instead multiply rapidly, piling up into inflamed patches.
“We have experimental data now to show what these patients with psoriasis are reporting,” said Dr Bollag, who nearly 20 years ago first reported that glycerine, a natural alcohol and water attractor known to help the skin look better, also safely helped it function better by helping skin cells mature properly.
Dr Bollag’s early report led to many anecdotal reports from individuals and their reports ultimately led to the newly published study.
Topically, glycerine is known to have a soothing, emollient effect. But once glycerine enters skin cells through the aquaporin 3 channel, the enzyme phospholipase-D-2 converts it to the lipid phosphatidylglycerol. Phosphatidylglycerol ultimately regulates the function of keratinocytes and suppresses inflammation in the skin. Dr Bollag and team previously reported that topical application of phosphatidylglycerol reduced inflammation and raised skin patches in a mouse model of psoriasis.
For this study, they focused on its glycerin precursor, which was either applied topically or fed to mice with induced psoriasis. Either way, glycerine helped reduce development of the characteristic skin lesions, showing that glycerin works in more than one way to improve the skin condition.
Glycerine worked as an emollient even in mice lacking phospholipase-D-2. It also seems to block hydrogen peroxide in the aquaporin 3 channel. At low levels, hydrogen peroxide is a cell signaling molecule, but at high levels results in destructive oxidative stress, possibly leading to psoriasis. Topical glycerine reduced the levels of hydrogen peroxide entering skin cells. When they added glycerin and hydrogen peroxide at the same time directly to skin cells, they found that glycerin protected against the oxidative stress from hydrogen peroxide.
“Glycerol is basically outcompeting the hydrogen peroxide in getting in there and preventing it from being able to enter and increase oxidative stress,” Dr Bollag said. Glycerine could also help by maintaining the skin’s water permeability barrier.
On the other hand, when glycerin was ingested by the mice missing the phospholipase- D-2, it simply did not work, Dr Bollag said, which confirmed their earlier findings that internally anyway, glycerine pairs with the enzyme to produce the signal essential to skin cell maturation.
Some of their other most recent work is detailing more about how phosphatidylglycerol decreases inflammation.
Dr Bollag would like next steps to also include clinical trials with dermatologists and patients and is working to find a formulation scientist who can make what she thinks will be the optimal combination: glycerin and phosphatidylglycerol in the same topical cream.
The addition of phosphatidylglyerol itself, rather than just the glycerine that makes it, is essentially a backup since there is some evidence that in psoriasis the essential conversion of glycerin to phosphatidylglycerol is not optimal. Dr Bollag’s lab and others have shown reduced levels of aquaporin 3 in psoriasis, which likely means less phosphatidylgycerol, so making more glycerine available could somewhat help raise the availability of this key lipid.
She suspects that this sort of two-punch combination, could help keep early signs of psoriasis at bay and, with more advanced disease, use existing psoriasis treatments to get the skin condition under control then start applying glycerin to help keep it that way.
While its exact cause is unclear, psoriasis is an immune-mediated condition and patients have higher levels of inflammation, as well as too many skin cells being produced then maturing abnormally. The heightened inflammation also puts them at increased risk for problems like heart disease.
Biologics used to treat psoriasis work different ways to stem this overactive immune response but in addition to their high cost, can put the patient at risk for problems like serious infections and cancer. The only side effect she has seen in about 20 years of working with glycerine and the clinical and cosmetic use already out there, is sticky-feeling skin.
A new study has found that there is a buildup of damaging DNA in the eyes of patients with geographic atrophy, an untreatable, poorly understood form of age-related macular degeneration that leads to blindness. Based on this, the researchers believe it may be possible to treat the condition with HIV drugs, or even simpler ones.
Dr Jayakrishna Ambati and colleagues had previously discovered that the harmful DNA, known as Alu cDNA, was manufactured in the cytoplasm. This represents the first time toxic Alu cDNA accumulation has been confirmed in patients in any disease.
“Although we’ve known that geographic atrophy expands over time, we didn’t know how or why,” said Dr Ambati, of UVA’s Department of Ophthalmology and Center for Advanced Vision Science. “Our finding in human eyes that the levels of toxic Alu cDNA are highest at the leading edge of the geographic atrophy lesion provides strong evidence that it is responsible for this expansion over time that leads to vision loss.”
Geographic atrophy is an advanced form of age-related macular degeneration, which ultimately destroys vital cells in the retina, resulting in blindness.
Dr Ambati, a leading expert in macular degeneration, and colleagues found that this destruction is brought about by the buildup of Alu DNA. As Alu DNA accumulates in the eye, it triggers harmful inflammation via the inflammasome. The researchers discovered the mechanism involving a previously unknown structural facet of Alu that triggers the immune response that destroys the retinal cells.
HIV drugs called nucleoside reverse transcriptase inhibitors, or NRTIs, could treat this; tests in lab mice suggest these drugs, or safer derivatives known as Kamuvudines, could block the harmful inflammation and protect against retinal cell death.
“Over the last two decades, dozens of clinical trials for geographic atrophy that have targeted other pathways have failed,” Dr Ambati said. “These findings from patient eyes provide a strong impetus for a new direction.”
Dr Ambati says his latest findings support clinical trials testing the drugs in patients with macular degeneration. A prior study of health insurance databases with over 100 million patients found that people taking NRTIs were almost 40% less likely to develop dry macular degeneration.
“Our findings from human eyes show that these toxic molecules, which activate the inflammasome, are most abundant precisely in the area of greatest disease activity,” Dr Ambati said. “We are very hopeful that a clinical trial of Kamuvudines will be launched soon in geographic atrophy so that we can potentially offer a treatment for this devastating condition.”
In a review of evidence for dental hygiene techniques, only a few were able to provide additional protection against gingivitis and periodontitis beyond brushing one’s teeth with a basic toothbrush.
At the moment, all other oral hygiene interventions are only supported by insufficient evidence, said principal investigator Frank Scannapieco, DMD, PhD, professor of oral biology in the UB School of Dental Medicine. The findings, he said, will help identify best practices for preventing gum disease.
“Patients can be confident that the oral care tools and practices supported by research, as described in the paper, will prevent the initiation and progression of periodontal disease, if they are performed regularly and properly,” said Prof Scannapieco.
The list of proven techniques includes: basic toothbrush; interdental brush; water pick; chlorhexidine gluconate (CHX), cetylpyridinium chloride (CPC) and essential oil (Listerine) mouth rinses. Tooth brushing is the cornerstone of daily oral hygiene and is a reliable way to control dental plaque, said Scannapieco. Interdental brushes and water picks also performed better than other interdental oral hygiene devices at reducing gingivitis, and both should be used in combination with daily tooth brushing to prevent gum disease.
Mouth rinses based on CHX, CPC, and essential oils (such as Listerine) were proven to be effective at significantly reducing plaque and gingivitis.
While not effective at fighting gingivitis, toothpicks were useful for monitoring gum health, said Prof Scannapieco. By gently prodding the gums with a toothpick and monitoring for bleeding, patients could detect signs of gum disease.
While triclosan toothpastes and mouth rinses significantly reduced plaque and gingivitis, the compound is linked to cancer development and reproductive defects, and has been removed from most toothpastes in the US. Unfortunately for those who invested in one, electric-powered toothbrushes are no more effective at reducing plaque and gingivitis than a basic toothbrush, the researchers found. And little evidence has been published in support of dental floss – the mainstay of interdental cleaning – to reduce plaque and gingivitis. However, Prof Scannapieco said that flossing is still necessary: “While there are few studies available that specifically examined toothbrushes or floss alone, both are still essential. Floss is especially useful to remove interdental plaque for people who have tight space between their teeth. Floss also likely reduces the risk for cavities that from between the teeth.” Evidence was lacking for mouthwashes based on tea tree oil, green tea, anti-inflammatory agents, hydrogen peroxide, sodium benzoate, stannous fluoride, hexetidine or delmopinol reduced gingivitis.
Though promising as a preventive strategy against gum disease, the effectiveness of probiotics was unproven. There was also little evidence for dietary supplements improving gum health. The investigators also found insufficient evidence that professional plaque removal (known as scaling, the process of removing plaque with a scraper) prevents gum disease.
Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which cause tuberculosis. Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Diabetes status may play a role in the risk for developing tuberculosis, suggests a new study reported in JAMA Network Open.
Diabetes and tuberculosis are two major problems for South Africa; an estimated 15% of the population 25 and over have type 2 diabetes, and the burden of tuberculosis was 774 per 100k population in 2012.
In the population-based study from Korea, adults with diabetes had a 48% greater risk for developing tuberculosis compared with adults without diabetes.
This increased tuberculosis risk also appeared to be tied to the duration of diabetes, with risk increasing the longer the person had diabetes:
New-onset diabetes: aHR 1.32 (95% CI 1.23-1.42)
Diabetes duration less than 5 years: aHR 1.45 (95% CI 1.36-1.54)
Diabetes duration 5 or more years: aHR 1.57 (95% CI 1.48-1.66)
The tuberculosis risk also seemed to be dependent on blood glucose levels. Individuals with impaired fasting glucose only, that is, blood glucose levels of 100-125 mg/dL but no diabetes diagnosis, did not appear to have an elevated risk of contracting tuberculosis.
However, those with new-onset diabetes in the highest decile of fasting blood glucose levels (202 mg/dL or higher) had a 79% greater risk for tuberculosis than those with lower glucose levels (fasting plasma glucose of 126-128 mg/dL).
The researchers noted that a previous study looking at this association found about a 2.2-fold increased risk of tuberculosis in patients with diabetes, including those with a fasting plasma glucose level over 130 mg/dL.
“Diabetes appears to be associated with increased risk of lower respiratory tract infection, including TB [tuberculosis], and to have a profound adverse effect on TB treatment outcomes,” the researchers explained. “Even though TB is more associated with other immunosuppressive states, such as human immunodeficiency virus infection, because of the greater numbers, diabetes remains an important factor associated with TB incidence at the population level.”
For the cohort study, the researchers drew upon data from the Korean National Health Insurance System database. Only patients without a history of tuberculosis were included. Besides a history of tuberculosis, other exclusion criteria included diagnoses of anaemia, cancer, and end-stage renal disease.
Individuals who had diabetes the longest tended to be older, have obesity, and possess more comorbidities like chronic kidney disease, chronic obstructive pulmonary disease, ischaemic heart disease, stroke, and dyslipidaemia.
During a median follow-up of about 8 years, 0.6% of the cohort were identified.
A study limitation was that fasting plasma glucose levels were only monitored once at baseline, and that changes in glucose level after treatment was over were not taken into consideration.
“Nevertheless, it is likely that patients whose diabetes status progressed as a result of poor glucose control during the follow-up duration would have a higher risk of TB,” the researchers wrote.
The link with tuberculosis was stronger in male patients, they noted: “The exact mechanism for this phenomenon is not fully explainable — testosterone could be a reason.”
GLP-1R agonists, a popular class of diabetes drugs, may also have a protective effect against glaucoma in diabetic patients, according to a new study published in the British Journal of Ophthalmology.
The researchers examined retrospective data of 1961 diabetic patients who were new users of this class of drugs and matched them to 4371 unexposed control subjects. After 150 days on average, 10 patients in the medicated group were newly diagnosed with glaucoma (0.5%) compared to 58 patients (1.3%) in the control group. These results indicate that GLP-1 receptor agonists could halve a diabetic patient’s risk of developing glaucoma.
The findings are supported by a Penn Medicine study from 2020, which found that GLP-1R agonists reduced neuroinflammation and prevented retinal ganglion cell death in mice. This class of drugs has also shown similarly protective effects against Alzheimer’s and Parkinson’s diseases in animal models, and clinical trials are underway to test the medications against neurodegenerative diseases in humans.
Glaucoma is the second leading cause of blindness worldwide, and people with diabetes are twice as likely to develop the condition.
“It was very encouraging to see that a popular diabetes medication could significantly reduce the risk of developing glaucoma, and our study suggests that these medications warrant further study in this patient population,” said Qi N. Cui, MD, PhD, with Brian VanderBeek, MD, MPH, both assistant professors of Ophthalmology at Penn.
