Tag: 8/6/22

Categories : Cardiovascular DiseaseTags : Leave a comment

RAAS Inhibitors Reduce Risk of Intracranial Aneurysm Rupture

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Credit: American Heart Association

The risk of intracranial aneurysm rupture was lower in people taking renin-angiotensin-aldosterone system (RAAS) inhibitors for hypertension, according to the findings of a Chinese study published in Hypertension.

A database with more than 3000 people with these aneurysms in 2016–2021, rupture rates reached 23.4% in RAAS inhibitor users and 76.6% in non-users.

RAAS inhibitor use was associated with a significantly reduced risk of intracranial aneurysm rupture (odds ratio [OR] 0.490), and this applied to angiotensin-converting enzyme (ACE) inhibitors (OR 0.559) and angiotensin receptor blockers (ARBs) alike (OR 0.414).

The RAAS inhibitors’ effect persisted across subgroups by age, sex, BMI, control of hypertension, monotherapy and combination therapy, and location and size of intracranial aneurysms.

The researchers pointed out the safety and affordability of RAAS inhibitors, and suggested that a randomised trial be conducted to confirm whether these medications protect against aneurysm rupture.

Hypertension is known to to increases the risk of intracranial aneurysm rupture, the cause of most subarachnoid haemorrhage strokes.

The authors note that there is evidence suggesting RAAS activation is involved in the pathogenesis of intracranial aneurysms.

“In hypertension, the RAAS has wide-ranging effects on blood pressure regulation through sodium retention, pressure natriuresis, salt sensitivity, vasoconstriction, endothelial dysfunction, and vascular injury. Given these facts, in addition to the directly increasing hemodynamic stresses, activation of the RAAS by systemic hypertension can cause vascular inflammation, injury, and remodeling and thereby contribute to the process of intracranial aneurysm rupture,” they explained.

How inhibiting RAAS would prevent aneurysm rupture was unclear, the authors noted, which could be investigated in a future study.

For this retrospective study, the authors reviewed the records of 3044 adults (mean age 61, 36.6% men) patients across 20 Chinese academic medical centres.

Patients were on blood pressure medications and had an intracranial aneurysm, and split between those whose aneurysms had ruptured (n = 1238) or had not ruptured (n = 1806) by the time of analysis. Aneurysms could be treated by clipping, coiling, and/or conservative treatment.

A secondary analysis matched 541 RAAS inhibitor users with an equal number of non-users, revealing that 17.7% of ruptured aneurysms would be prevented if all patients took RAAS inhibitors.

Besides RAAS inhibitor non-use, other independent predictors of rupture included female sex, passive smoking, uncontrolled or unmonitored hypertension, hyperlipidaemia, and aneurysmal location outside the internal carotid artery.

“Our study importantly extends previous studies of blood pressure control, treating hyperlipidemia and diabetes aggressively, and avoiding passive smoking as second [prevention] for these patients,” the authors wrote.

Limitations include possible confounding variables, as well as key clinical variables, such as blood pressure measurements and duration and dose of RAAS inhibitor therapy not being included in the database.

Source: MedPage Today

Categories : Diseases, Syndromes and ConditionsTags : Leave a comment

Keratinocytes Play a Role in Stable Vitiligo Disease

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Targeting keratinocyte metabolism could be a new method of vitiligo treatment. Photo by Hanen BOUBAHRI on Unsplash

A new study published today in JCI Insight reveals the unique cell-to-cell communication networks that can perpetuate inflammation and prevent repigmentation in patients with stable vitiligo disease, and the particular role that keratinocytes play.

“In this study, we couple advanced imaging with transcriptomics and bioinformatics to discover the cell-to-cell communication networks between keratinocytes, immune cells and melanocytes that drive inflammation and prevent repigmentation caused by vitiligo,” said Anand K. Ganesan, MD, PhD, professor at University of California, Irvine. “This discovery will enable us to determine why white patches continue to persist in stable vitiligo disease, which could lead to new therapeutics to treat this disease.”

Vitiligo is an autoimmune skin disease characterised by the progressive destruction of melanocytes by immune cells called autoreactive CD8+ T cells, resulting in disfiguring patches of white depigmented skin. This disease has shown to cause significant psychological distress among patients. Melanocyte destruction in active vitiligo is mediated by CD8+ T cells, but until now, why the white patches in stable disease persist was poorly understood.

“Until now, the interaction between immune cells, melanocytes, and keratinocytes in situ in human skin has been difficult to study due to the lack of proper tools,” said Jessica Shiu, MD, PhD, assistant professor of dermatology and one of the first authors of the study. “By combining non-invasive multiphoton microscopy (MPM) imaging and single-cell RNA sequencing (scRNA-seq), we identified distinct subpopulations of keratinocytes in lesional skin of stable vitiligo patients along with the changes in cellular compositions in stable vitiligo skin that drive disease persistence. In patients that responded to punch grafting treatment, these changes were reversed, highlighting their role in disease persistence.”

MPM is a unique tool that has broad applications in human skin. MPM is a noninvasive imaging technique capable of providing images with sub-micron resolution and label-free molecular contrast which can be used to characterise keratinocyte metabolism in human skin.

Most studies on vitiligo have focused on active disease, while stable vitiligo remains somewhat of a mystery. Studies are currently investigating when metabolically altered keratinocytes first appear and how they may affect the repigmentation process in patients undergoing treatment.

The study findings suggest the possibility of targeting keratinocyte metabolism in vitiligo treatment. Further studies are needed to improve the understanding of how keratinocyte states affect the tissue microenvironment and contribute to disease pathogenesis.

Source: University of California – Irvine

Categories : Allergies Diet and NutritionTags : Leave a comment

Dietary Fibre Shown to Protect Against Atopic Dermatitis

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Research suggests that the gut-skin axis may have an influence on skin conditions. Photo by Romina Farias on Unsplash

A study published in Mucosal Immunology into the emerging gut-skin axis has found that microbial fermentation of dietary fibre in the gut can protect against atopic dermatitis. The research could potentially lead to novel treatments to prevent or treat allergies.

The Monash University led by Professor Ben Marsland showed that fermentation of fibre in the gut by bacteria and subsequent production of short chain fatty acids (SCFAs), in particular butyrate, protected against atopic dermatitis in mice.

Previous work had found that dietary fibre was connected to protection against flu through SFCAs activating cytotoxic T cells. SCFAs are also often found in sources including root vegetables such as chicory roots or the skins of citrus fruits

While it is well established that the gut microbiome shapes the immune system, the influence it has on the skin is less explored.

“Previous work from our group, and others, has focused on the local health benefits of SCFAs in the gut as well as at distal sites such as the lung and cardiovascular system,” Professor Marsland said. “We wondered if this might also extend to the skin, which is an area that has not really been investigated.

“People speculate that diet can influence skin health, but there is not a great deal of science behind this.”

The researchers fed mice a diet high in fermentable fibre or gave them purified SCFAs. “This treatment was profoundly protective against allergic skin inflammation,” Professor Marsland said.

They labelled the butyrate with isotopes and tracked it in the body, taking only minutes to reach the skin where it enhanced the metabolism of keratinocytes, priming them to mature and produce the key structural components required for a healthy skin barrier.

“The upshot of this was that the skin barrier was fortified against allergens – we were using house dust mite allergens – that would normally penetrate the skin barrier, activate the immune system and start an allergic reaction in these models,” he said.

“It turns out the immune system was secondary to this skin barrier function.”

Actively improving the skin barrier could have protective effects against environmental exposures that cause allergies and perhaps even other skin diseases which are underpinned by a damaged or weak skin barrier. SCFAs could be administered orally or directly on the skin as a cream, bypassing the gut, he said.

“The fact that short chain fatty acids can be given topically and are well-tolerated opens up possibilities for development of preventative strategies or disease-modifying interventions – that represents the most significant translational potential of our research.”

One possibility to explore is whether this could help children who are at risk of developing skin allergies that cascade towards food allergies and asthma, the so-called ‘Atopic March’.

Source: Monash University

Categories : Cardiovascular Disease Implants and ProsthesesTags : Leave a comment

Deep Nerve Stimulation Controls Blood Pressure

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Blood pressure cuff
BP cuff for home monitoring. Source: Pixabay

A study published in Frontiers in Neuroscience demonstrated that blood pressure and renal sympathetic nerve activity (RSNA) can be controlled by bioelectronic treatment. RSNA is often increased in hypertension and renal disease.

Using a custom-wired electrode, Professor Mario Romero-Ortega previously reported that deep peroneal nerve stimulation (DPNS) elicits an acute reduction in blood pressure. The current study, advances that work, focusing on his development of a small implantable wireless neural stimulation system and exploration of different stimulation parameters to achieve a maximum lowered response.

Prof Romero-Ortega integrated a nerve stimulation circuit less than a millimetre in size, with a novel nerve attachment microchannel electrode that can be implanted into small nerves, while enabling external power and DPNS modulation control.

Using this implantable device, his team demonstrated that systolic blood pressure can be lowered 10% in one hour and 16% two hours after nerve stimulation.

“Our results indicate that DPNS consistently induces an immediate and reproducible arterial depressor effect in response to electrical stimulation of the deep peroneal nerve,” reported Prof Romero-Ortega.

While pharmacological treatments are effective, blood pressure remains uncontrolled in 50–60% of resistant hypertensive subjects. Unfortunately, despite the use of multiple antihypertensive drugs in combination, blood pressure remains poorly controlled in 50–60% of the hypertensive population and approximately 12–18% of them develop resistant hypertension, defined as blood pressure greater than 140/90 mmHg despite the use of antihypertensive drugs.

“In this study, DPNS induced an initial increase in RSNA during the first 2–3 seconds, followed by a reduction in renal activity and mean arterial pressure, despite the increase in heart rate,” said Prof Romero-Ortega. “The observed activation of the RSNA during the DPNS was not expected since its activity is associated with hypertension.”

Source: University of Houston

Categories : Pain ManagementTags : Leave a comment

Cannabis is Moderately Effective for Chronic Pain, Review Finds

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Cannabis’s pain reduction effects appear to be less effective than previously though. Photo by Kindel Media

Cannabis product use provides modest, short-term improvements in chronic pain, albeit with some side effects, according to a large review of research on cannabis pain management. The review also revealed a general lack of high quality evidence such as randomised controlled trials (RCTs). The data will be uploaded to a web app made by Oregon Health & Science University to inform clinicians on cannabis medications.

Reporting in Annals of Internal Medicine, researchers found evidence to support a short-term benefit in treating neuropathic pain with two synthetic products with 100% tetrahydrocannabinol (THC): dronabinol (under the trade name Marinol) and nabilone (Cesamet). Another product, a sublingual spray of equal parts THC and cannabidiol (CBD), known as nabiximols, also showed evidence of some clinical benefit for neuropathic pain. All of the products had side effects, such as nausea, sedation and dizziness.

From 3000 studies, the researchers selected RCTs or comparative observational studies of patients with chronic pain that compared cannabis products with a placebo or no treatment (that is, usual care) for at least 4 weeks of treatment or follow-up.

They ended up with a total of 25 with scientifically valid evidence – 18 RCTs and seven observational studies. Cannabinoids were categorised as high, comparable, or low THC-to-CBD ratio. The researchers found:

  • Synthetic products with high THC (> 98%) and little or no CBD: moderate improvement in pain, but greater sedation risk and possible increase in dizziness
  • Extracted products with majority THC (THC:CBD ratio ranging from 3:1 to 47:1): no significant improvement in pain, but greater study withdrawal because of adverse events and dizziness
  • Sublingual sprays with comparable THC and CBD levels: small improvement in pain but a much greater increased risk of dizziness and sedation and a moderate increase in nausea

Besides these findings, there was little evidence to support any other conclusions.

“In general, the limited amount of evidence surprised all of us,” said lead author Marian S. McDonagh, PharmD, emeritus professor at OHSU. “With so much buzz around cannabis-related products, and the easy availability of recreational and medical marijuana in many states, consumers and patients might assume there would be more evidence about the benefits and side effects.

“Unfortunately, there is very little scientifically valid research into most these products. We saw only a small group of observational cohort studies on cannabis products that would be easily available in states that allow it, and these were not designed to answer the important questions on treating chronic pain.”

“For some cannabis products, such as whole-plant products, the data are sparse with imprecise estimates of effect and studies had methodological limitations,” the authors noted.

This situation makes it difficult to guide patients.

“Cannabis products vary quite a bit in terms of their chemical composition, and this could have important effects in terms of benefits and harm to patients,” said co-author Roger Chou, MD. “That makes it tough for patients and clinicians since the evidence for one cannabis-based product may not be the same for another.”

The living review, including a visual abstract summary of the findings, will also be shared on a new web-based tool launched by OHSU and VA Portland Health Care System early this year to help clinicians and researchers evaluate the latest evidence around the health effects of cannabis. Known as Systematically Testing the Evidence on Marijuana, or STEM, the project includes ‘clinician briefs’ to help health care workers translate the clinical implications.

“This new living evidence review is exactly the type of resource clinicians need to clarify for patients the areas of potential promise, the cannabis formulations that have been studied and, importantly, the major gaps in knowledge,” said co-author Devan Kansagara, MD, MCR, professor of medicine at OHSU.

Source: Oregon Health & Science University