Category: Diseases, Syndromes and Conditions

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Tecovirimat Safe and Effective against Monkeypox

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Colourised transmission electron micrograph of monkeypox virus particles (green) cultivated and purified from cell culture. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland. Credit: NIAID

In a research letter published in JAMA, infectious disease experts reported on 25 monkeypox patients given tecovirimat therapy, with data showing that it is safe and effective for the treatment of monkeypox symptoms and skin lesions.

The recent global outbreak of monkeypox has led to more than 45 500 cases as of August 22, 2022. While symptoms usually resolve on their own in 2–4 weeks, a recent study showed that 13% of patients needed hospitalisation.

Tecovirimat (TPOXX) is an FDA-approved antiviral drug for the treatment of smallpox which limits viral spread in the body by inhibiting the release of the enveloped virus. Recently, the Centers for Disease Control and Prevention (CDC) allowed physicians to prescribe tecovirimat on a compassionate use basis to treat adults and children with orthopoxvirus infections, including monkeypox.

“We have very limited clinical data on the use of tecovirimat for monkeypox infection. There is much to learn about the natural progression of the disease and how tecovirimat and other antivirals may affect it,” said lead author Angel Desai, an adult infectious disease specialist.

The new study included patients referred to UC Davis Medical Center, between June 3 and August 13, 2022.

Patients with skin lesions in multiple body parts or in sensitive areas such as the face or genital region were offered oral tecovirimat treatment. The treatment was weight-based, given every 8 or 12 hours, and was taken within 30 minutes of a high-fat meal.

The researchers collected clinical data on evaluation for treatment and on day 7 and day 21 following the beginning of therapy.

In total, 25 male patients (ages 27–76 years) with confirmed monkeypox infection completed a course of tecovirimat therapy. Nine patients had HIV.

Only one patient had the smallpox vaccine (taken more than 25 years ago) and four others received a dose of JYNNEOS vaccination after symptoms started.

The study found that 92% of patients had lesions in their genital or anal area. While all patients had painful lesions, around half had fewer than 10 lesions over their entire body.

On average, the patients had symptoms or lesions for 12 days before they started their antiviral treatment. Fever was the most common symptom (76% of the patients), followed by fatigue (32%), sore throat (20%) and chills (20%). Other symptoms included backache (12%), muscle pain (8%), nausea (4%) and diarrhoea (4%).

All patients completed the tecovirimat therapy and tolerated their treatment well. They were treated for two weeks, except for one patient who was treated for 21 days.

On day 7 of therapy, 40% of patients had healed from their lesions. By day 21, 92% had healed and were pain-free.

The most reported adverse events on day 7 of therapy included: fatigue (28%), headache (20%), nausea (16%), itching (8%) and diarrhoea (8%).

“We have to be very careful in how we interpret the data. It is hard to differentiate the side effects due to therapy from those caused by the infection,” cautioned infectious diseases expert and co-author George Thompson.

This small study lacked a control group, limiting assessment of antiviral efficacy in terms of symptom duration and severity. Also, the time from symptom onset to starting the antiviral therapy varied among the patients.

The researchers called for large-scale studies to explore antiviral efficacy dosing and adverse events.

Source: UC Davis Health

Categories : Diseases, Syndromes and Conditions Environmental EffectsTags :

Wealth Divide, not Vitamin D, Explains Differing MS Rates

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Photo by Kyle Glenn on Unsplash

Differences in vitamin D exposure have been thought to explain why people who live farther from the equator are more likely to develop multiple sclerosis (MS). But countries farther from the equator are also more likely to be wealthier. A new analysis published in Neurology shows that the amount a country spends on health care may help explain this relationship between MS and latitude.

According to study author Deanna Saylor, MD, MHS, the results suggest that MS rates may be greatly underestimated in low-income countries with lower health care spending, which means that people have less access to neurologists who have the expertise to diagnose MS and MRI scanners that are needed to make the diagnosis.

Researchers analysed data from scientific studies and databases to determine current rates of MS in 203 countries and territories. Countries were then grouped into world regions and by income levels.

Rates of MS varied by region and income level. For example, in high-income countries an average of 46 of every 100 000 people had MS, compared to 10 people per 100 000 in low-income countries. Health care spending per capita was $2805 for high-income countries, compared to $45 in low-income countries.

For each location, researchers examined gross domestic product per capita, current health expenditure per capita, income levels, the availability of brain scans to diagnose MS, the number of neurologists per capita and universal health care. They also reviewed lifestyle factors such as obesity and tobacco use.

Once the researchers adjusted the data for other factors that could affect the risk of MS, such as age and sex, they found that health care spending and latitude were strongly associated with MS rates. The research showed that, with every increase of one standard deviation in health expenditure per capita, a country’s MS prevalence increased by 0.49. Alternatively, with every increase of one standard deviation in latitude, a country’s MS prevalence increased by 0.65.

Researchers also found that health care spending explained some, but not all, of the link between latitude and MS. After adjusting for other factors, the link between latitude and MS decreased by more than 20% when health care expenditure per capita was considered.

The availability of universal health care was associated with rates of MS in all world regions, except Southeast Asia, with universal health care tied to higher rates of MS.

In high-income countries, rates of MS were linked to most factors, including gross domestic product per capita, current health expenditure per capita, and the number of neurologists, but not tobacco use and obesity or the number of MRI units per capita. However, in low-income countries, there were no associations with any of these factors, which may be explained by a lack of significant variation in data from these countries, Saylor said.

According to Dr Saylor, the finding that current health expenditure per capita was very strongly linked with national rates of MS further supports the hypothesis that greater investment in health care leads to more robust reporting of rates of MS. She also said the minimal links between rates of MS and lifestyle factors such as tobacco use and obesity run counter to prior assumptions that lifestyle and consumption behaviours explain the large portions of regional differences in reported rates of MS.

Dr Saylor said strategies are urgently needed for the accurate assessment of the burden of MS in low-income countries, and these lower reported MS can obscure the need for training and funding regarding MS.

A limitation of the study is that different data sources may have collected information during different time periods or used different methods, which could affect the accuracy of estimates.

Source: American Academy of Neurology

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Traditional Japanese Herbal Medicine Found to Alleviate Colitis

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Gut microbiome. Credit: Darryl Leja, NIH

A Japanese study published in Frontiers in Immunology shows that a traditional herbal mix called daikenchuto reduced the severity of colitis in lab mice by preventing the loss of important gut bacteria and by raisin levels of anti-inflammatory immune cells in the colon.

Colitis is a chronic inflammation of the colon, characterised by an imbalance in gut bacteria and an abnormal immune response. Its prevalence has doubled over the last 20 years and although there are many treatments, they are only partially effective. This has led some researchers to take a closer look at traditional Asian herbal medicines.

Daikenchuto (DKT) is a formula containing specific amounts of ginger, pepper, ginseng, and maltose, and is one of 148 herbal medicines called Kampo, which have been developed in Japan and are often prescribed by doctors to treat a variety of illnesses. Numerous studies conducted in Japan and the United States have provided clinical evidence of DKT’s effect on colonic transit and postoperative ileus.

DKT was shown by previous research to have possible use in colitis treatment, but molecular level evidence has been lacking. Researchers at the RIKEN Center for Integrative Medical Sciences (IMS) in Japan conducted a detailed examination of its effects on a mouse model of colitis.

Colitis was induced in mice using dextran sodium sulfate, which is toxic to the cells that line the colon. When these mice were given DKT, their body weights remained normal, and they had lower clinical scores for colitis. Additional analysis revealed much less damage to the cells lining the colon. Having thus shown that DKT does indeed help protect against colitis, the researchers proceeded to analyze the gut microbiome of the mice and expression levels of anti-inflammatory immune cells.

Colitis is associated with an imbalance in gut microbiota, and analysis showed that a family of lactic acid bacteria were depleted in the colitic mice of this study. Also depleted was one of their metabolites, a short-chain fatty acid called propionate. Treating the model mice with DKT restored much of these missing bacteria – particularly Lactobacillus – and levels of propionate were normal.

Colitis is also associated with an abnormal immune response that causes the characteristic intestinal inflammation. When the team looked at innate intestinal immune cells, they found that levels ILC3 cells were lower in the untreated colitic mice than in the DKT-treated colonic mice, and that mice engineered to lack ILC3 suffered more and could not benefit from DKT treatment. This means that ILC3s are critical for protecting against colitis and that DKT works by interacting with them. Lastly, qPCR analysis indicated that these important immune cells had receptors for propionate, called GPR43, on their surface.

“Daikenchuto is commonly prescribed to prevent and treat gastrointestinal diseases, as well as for reducing intestinal obstruction after colorectal cancer surgery,” said Naoko Satoh-Takayama. “Here we have shown that it can also alleviate intestinal diseases like colitis by rebalancing Lactobacillus levels in the gut microbiome. This likely helps reduce inflammatory immune responses by promoting the activity of type 3 innate lymphoid cells.”

Source: RIKEN

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For Acne Scars in Dark Skin, Microneedling Beats Chemical Peels

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Chemical peels are a common treatment for acne scars, but a study published in the Journal of Clinical and Aesthetic Dermatology finds that, for patients with dark skin, microneedling is a significantly more effective treatment.

Researchers randomly assigned 60 patients with acne scars and dark skin (Fitzpatrick Skin Phototype IV to VI) to treatment with either 35% glycolic acid chemical peels or microneedling, both administered every two weeks for 12 weeks.

Microneedling therapy is a controlled skin injury that utilises instruments containing rows of thin needles that penetrate the dermis to a uniform depth. This induces rapidly-healing micropunctures with subsequent stimulation of collagen and elastin fibre production, resulting in skin remodelling.

Microneedling was initially developed as a tool for skin rejuvenation. However, it is now being used for a number of indications, which include: various forms of scars, alopecias, drug delivery, hyperhidrosis, stretch marks, and more. It is occasionally combined with delivery of radiofrequency energy, which is thought to enhance dermal remodelling and clinical effects. Despite its widespread use, data on the efficacy of microneedling are lacking.

Chemical peels involve applying a solution to the skin that removes the top layers.

Treatment produced an improvement of two points or more on the Goodman and Baron Scarring Grading System in 33% of patients who received chemical peels and 73% of patients who underwent microneedling.

“Based on the results of this study, patients whose darker skin precludes the use of stronger chemical peels, which can permanently discolour darker skin, should treat acne scars with microneedling,” said the study’s senior author Babar Rao, a professor of dermatology and pathology at Robert Wood Johnson Medical School. “For patients with lighter skin who can use stronger peels without risk of discoloration, chemical peels might still be the best option for some.”

Source: EurekAlert!

Categories : Diseases, Syndromes and Conditions New Compounds and TreatmentsTags :

Promising New Lupus Pill Reverses Organ Damage in Mice

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The autoimmune disease lupus has no cure, and current treatment is limited in its effectiveness in reducing symptoms and controlling damage to the body. Now, scientists report they have begun phase 2 clinical trials with a compound that, in mice, not only prevents lupus-like symptoms, but also reverses signs of organ damage caused by the disease and prevents death.

“Few new therapies have succeeded, but we believe our compound could be an effective treatment for lupus,” says Alaric Dyckman, PhD. The disease affects 5 million people worldwide, according to the Lupus Foundation of America. Symptoms include rashes, extreme fatigue, pain, inflammation and deterioration of organs, such as the kidneys and heart, which can lead to death.

The researchers will present their results at the fall meeting of the American Chemical Society (ACS). ACS Fall 2022 is a hybrid meeting being held virtually and in-person Aug. 21–25, with on-demand access available Aug. 26–Sept. 9.

Lupus develops when the immune system attacks the body’s tissues. Years ago, researchers began suspecting that this process involved toll-like receptors (TLRs) 7 and 8, which are cellular proteins that activate the immune system when they detect viral RNA or mistakenly identify a person’s own RNA as a threat.

“Genetic data and evaluations of injectable treatments suggested TLR7 and 8 could be drug targets for lupus. What was missing was an ability to directly block these receptors with small molecules that could be taken orally,” explained Dr Dyckman. So in 2010, he and other scientists at Bristol Myers Squibb (BMS) set out to develop such compounds.

New options would be welcome, since many patients don’t respond fully to current medications. The two approved therapies that were specifically developed for lupus reduce activity of specific immune system components: AstraZeneca’s anifrolumab blocks an interferon receptor, while GlaxoSmithKline’s belimumab reduces the survival of B cells. Other treatments include steroids and other general immune suppressants, anti-malarials, anti-inflammatories and anticoagulants. However, anifrolumab and belimumab must be given by injection or infusion, Dr Dyckman noted, while steroids and general immune suppressants are associated with safety concerns and were not originally designed to treat lupus.

The BMS researchers started by screening the company’s compound collection for molecules that could block TLR7/8 signalling. The team refined the search further to improve interaction with other receptors, and potency, and enablee oral dosing. The resulting compound, afimetoran, binds to the target TLRs, inhibiting their operation to achieve beneficial activity. Like anifrolumab, it interferes with interferon, and like belimumab, it controls damage from overactive B cells. It also inhibits the production of multiple proinflammatory cytokines that cause a lot of tissue damage in lupus.

“With afimetoran, not only could we prevent the development of lupus-like symptoms in mice before their disease onset, but we could actually reverse the symptoms and prevent death in animals that were days or weeks away from succumbing to the disease,” Dr Dyckman said. “We hadn’t seen that reversal with other mechanisms we had evaluated, so we were particularly excited about that finding.” Dr Dyckman said that he believes afimetoran effects together may let it control lupus as well as or better than existing treatments, doing it through an oral route.

Afimetoran also combined well with corticosteroid treatments in mice, so patients might be able to use lower doses of steroids and reducing associated side effects.

Phase 1 clinical trials of afimetoran have been completed. The trials showed that a low, once-daily oral dose was safe in healthy patients and could almost completely block signalling through TLR7/8. And now, a phase 2 trial to test its effectiveness in lupus patients is underway. Because of its mode of action, Dr Dyckman said, it may also work in other autoimmune disorders, such as psoriasis or arthritis.

BMS is testing other compounds against lupus, such as deucravacitinib, an oral, selective tyrosine kinase 2 (TYK2) inhibitor that is moving into phase 3 studies. Other companies are also making progress. Merck, for instance, is evaluating its own oral TLR7/8 blocker, enpatoran, in phase 2 trials.

Despite intensive efforts to develop new therapies over the past several decades, few have succeeded. “So getting a lot of shots on goal is important,” Dr Dyckman said. “Also, lupus is such a heterogeneous disease that it’s unlikely that any single approach will provide relief for all of the patients out there.”

Source: EurekAlert!

Categories : Diseases, Syndromes and Conditions Obstetrics & GynaecologyTags :

Caesarean Delivery may Increase Risk of Developing Crohn’s Disease

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Photo by Christian Bowen on Unsplash

A population-based study analysing over one million individuals suggests that babies born via caesarean section delivery may face a higher risk of developing Crohn’s disease later in life. The findings, published in Acta Obstetricia et Gynecologica Scandinavica, add to a growing body of evidence on long-term impacts of caesarean section delivery. 

More and more people are being delivered by caesarean section, and there is interest in understanding possible long-term health consequences of this mode of delivery. One possible route is through a lack of the early exposure of the infant to colonising bacteria via a vaginal delivery. Previous studies suggest that infants delivered by CS are at increased risks of disorders involving the immune system, such as asthma and allergies, type 1 diabetes, celiac disease, obesity, immune deficiencies, and leukaemia and other malignancies affecting young people.

In this study, all full-term individuals registered in the Medical Birth Register in Sweden between 1990 and 2000 were followed until 2017. Among 1 102 468 individuals, of whom 11.6% were delivered by caesarean section and 88.4% were vaginally delivered, caesarean section was associated with a 14% higher risk of developing Crohn’s disease after adjusting for confounding factors. No associations between delivery mode and appendicitis, ulcerative colitis, cholecystitis, or diverticulosis were found.

“Our study is the largest in this field, showing new interesting associations between caesarean section and increased risk later in life for Crohn’s disease. We hypothesise that the underlying mechanism could be the gut microbiome, but further studies will have to confirm this,” said senior author Anna Löf Granström, of the Karolinska Institute.

Source: Wiley

Categories : Diseases, Syndromes and Conditions Lab Tests and ImagingTags :

Low Serum Urate Increases Sarcopenia Risk

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Blood sample being drawn
Photo by Hush Naidoo Jade Photography on Unsplash

Adults with low blood levels of urate, the end-product of the purine metabolism in humans, may be at higher risk of sarcopenia and may face a higher risk of early death, according to a new study published in Arthritis & Rheumatology.

Whether or nor low serum urate (SU) levels contribute to adverse outcomes has been the subject of controversy.  The study involved 13 979 participants aged 20 years and older, sourced from the National Health and Nutrition Examination Survey from 1999–2006.

Low serum urate concentrations (<2.5 mg/dL in women; <3.5 mg/dL in men) were associated with low lean mass, underweight BMI (<18.5 kg/m2), and higher rates of weight loss. While low SU was associated with increased mortality (61%) before adjusting for body composition, its effect was reduced and non-significant after adjustment for body composition and weight loss.

“These observations support what many have intuited, namely that people with low serum urate levels have higher mortality and worse outcomes not because low urate is bad for health, but rather that low urate levels tend to occur among sicker people, who have lost weight and have adverse body composition,” explained lead author Joshua F. Baker, MD, MSCE, of the University of Pennsylvania. “While this observational study doesn’t disprove a causal association, it does suggest that great care is needed in interpreting epidemiologic associations between urate levels and health outcomes.”

Source: Wiley

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Asymptomatic Detection of Monkeypox Suggests it is More Widespread

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Colourised transmission electron micrograph of monkeypox virus particles (green) cultivated and purified from cell culture. Credit: NIAID

A brief research report in Annals of Internal Medicine documents positive monkeypox virus PCR results found in anal samples taken from asymptomatic MSM (men who have sex with men). These findings suggest that vaccination limited to those with known exposure to the monkeypox virus may not be an effective strategy for preventing infection.

The findings come as the World Health Organization has renamed the variants, or clades, of monkeypox from their previous geographically-derived names to Roman numerals, eg, the former Congo Basin (Central African) clade is now Clade one (I). It is also seeking inputs on a possible new name for the virus in order to avoid stigmatisation.

Researchers from Bichat–Claude Bernard Hospital, Paris, retrospectively performed testing for monkeypox virus on all anorectal swabs that were collected as part of a sexually transmitted infection screening program. This type of screening is performed every three months among MSM with multiple sexual partners who are either taking HIV preexposure prophylaxis (PrEP) or living with HIV and receiving antiretroviral treatment. Of the 200 asymptomatic persons screened that were negative for N. gonorrhoeae and C. trachomatis, 13 (6.5%) samples were PCR positive for monkeypox virus.  Two of the 13 later developed symptoms of monkeypox.

While it is not know whether asymptomatic transmission will play a role in the current worldwide monkeypox epidemic and the mode of human-to-human transmission may provide evidence that asymptomatic or preclinical spread can occur. In an accompanying editorial, Stuart N. Isaacs, MD, at the University of Pennsylvania, suggests that an expanded ring vaccination strategy and other public health interventions in the highest-risk communities are likely needed to help control the outbreak. 

Source: EurekAlert!

Categories : Diseases, Syndromes and ConditionsTags :

A Breakthrough Tinnitus Therapy – on a Smartphone

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Photo by Dylann Hendricks | 딜란 on Unsplash

After 20 years searching for a cure for tinnitus, for which there is no pharmacological treatment, there are ‘encouraging results’ from a clinical trial of a smartphone app therapy, the results of which have been published in Frontiers in Neurology.

The study randomised 61 patients to one of two treatments, the prototype of the new ‘digital polytherapeutic’ or a popular self-help app producing white noise. On average, the group with the polytherapeutic (31 people) showed clinically significant improvements at 12 weeks, while the other group (30 people) did not.

“This is more significant than some of our earlier work and is likely to have a direct impact on future treatment of tinnitus,” said Associate Professor in Audiology at the Universirt of Auckland, Dr Grant Searchfield.

Key to the new treatment is an initial assessment by an audiologist who develops the personalised treatment plan, combining a range of digital tools, based on the individual’s experience of tinnitus.

“Earlier trials have found white noise, goal-based counselling, goal-oriented games and other technology-based therapies are effective for some people some of the time,” says Dr Searchfield.

“This is quicker and more effective, taking 12 weeks rather than 12 months for more individuals to gain some control.”

“What this therapy does is essentially rewire the brain in a way that de-emphasises the sound of the tinnitus to a background noise that has no meaning or relevance to the listener,” Dr Searchfield says.

Audiology research fellow Dr Phil Sanders says the results are exciting and he found running the trial personally rewarding.

“Sixty-five percent of participants reported an improvement. For some people, it was life-changing – where tinnitus was taking over their lives and attention.”

Some people didn’t notice an improvement and their feedback will inform further personalisation, Dr Sanders noted.

Tinnitus is a phantom noise and its causes are complex. It has so far defied successful treatment.

While most people experience tinnitus, or ringing in the ears at least on occasions, around five percent experience it to a distressing degree. Impacts can include trouble sleeping, difficulty carrying out daily tasks and depression.

Dr Searchfield says seeing his patients’ distress and having no effective treatment to offer inspired his research. “I wanted to make a difference.”

The next step will be to refine the prototype and proceed to larger local and international trials with a view to FDA approval.

The researchers hope the app will be clinically available in around six months.

Source: University of Auckland

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Chronic Inflammation Link to Low Vitamin D Explains Some Controversies

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Vitamin D pills
Photo by Michele Blackwell on Unsplash

New genetic research shows a direct link between low vitamin D levels and high levels of inflammation, providing an important biomarker to identify people at higher risk of or severity of chronic illnesses with an inflammatory component, such as type 2 diabetes. The findings, published in the International Journal of Epidemiology, also helps to settle some of the controversies surrounding the ‘sunshine vitamin’.

The study drew on genetic data for 294 970 participants in the UK Biobank, using Mendelian randomisation to show the association between vitamin D and C-reactive protein levels, an indicator of inflammation.

University of South Australia’s Dr Ang Zhou, the study’s lead researcher, said that the findings suggest that boosting vitamin D in people with a deficiency may reduce chronic inflammation.

“This study examined vitamin D and C-reactive proteins and found a one-way relationship between low levels of vitamin D and high levels of C-reactive protein, expressed as inflammation.

“Boosting vitamin D in people with deficiencies may reduce chronic inflammation, helping them avoid a number of related diseases.”

The study also raises the possibility that having adequate vitamin D concentrations may mitigate complications arising from obesity and reduce the risk or severity of chronic illnesses with an inflammatory component, such as CVDs, diabetes, and autoimmune diseases.

Senior investigator and Director of UniSA’s Australian Centre for Precision Health, Professor Elina Hyppönen, said that these results offer an explanation for some of the controversies in reported associations with vitamin D.

“We have repeatedly seen evidence for health benefits for increasing vitamin D concentrations in individuals with very low levels, while for others, there appears to be little to no benefit.” Prof Hyppönen said.

“These findings highlight the importance of avoiding clinical vitamin D deficiency, and provide further evidence for the wide-ranging effects of hormonal vitamin D.”

Source: University of South Australia