Tag: 19/11/21

A New Alternative to Skin Biopsies

Source: Pixabay

A new ‘virtual histology’ technology being developed by researchers could replace many skin tissue biopsies. The technology is detailed in Light: Science & Applications

Histology is the microscopic study of tissues and organs through sectioning, staining, and examining those sections under a microscope. Often called microscopic anatomy and histochemistry, histology allows for the visualisation of tissue structure and characteristic changes the tissue may have undergone.

“This process bypasses several standard steps typically used for diagnosis – including skin biopsy, tissue fixation, processing, sectioning and histochemical staining. Images appear like biopsied, histochemically stained skin sections imaged on microscope slides,” said the study’s senior author, Aydogan Ozcan, Chancellor’s Professor and Volgenau Chair for Engineering Innovation of the Electrical and Computer Engineering Department at UCLA Samueli.

The technology may enable rapid diagnosis of malignant skin tumours, reducing unnecessary invasive skin biopsies and allowing skin cancer diagnosis at an earlier stage. This technology had only previously been applied to microscopy slides of unstained tissue, acquired through a biopsy. This is the first time virtual histology has been applied to intact, unbiopsied tissue.

“The current standard for diagnosing skin diseases, including skin cancer, relies on invasive biopsy and histopathological evaluation. For patients, this often leads to unnecessary biopsies and scars as well as multiple visits to doctors. It also can be costly for patients and the health care system,” said Dr Philip Scumpia, assistant professor of dermatology and dermatopathology at the David Geffen School of Medicine at UCLA and the West Los Angeles Veterans Affairs Hospital and a member of the UCLA Jonsson Comprehensive Cancer Center. “Our approach potentially offers a biopsy-free solution, providing images of skin structure with cellular-level resolution.”

The research team, led by Ozcan, Scumpia and Dr. Gennady Rubinstein, a dermatologist at the Dermatology & Laser Centre in Los Angeles, created a deep-learning framework to transform images of intact skin acquired by an emerging noninvasive optical technology, reflectance confocal microscopy (RCM), into a format that is user-friendly for dermatologists and pathologists. Analysing RCM images requires special training because they are in black and white, and unlike standard histology, they lack nuclear features of cells.

“I was surprised to see how easy it is for this virtual staining technology to transform the images into ones that I typically see of skin biopsies that are processed using traditional chemical fixation and tissue staining under a microscope,” Dr Scumpia said.

The researchers trained a neural network to rapidly transform RCM images of unstained skin into virtually stained 3D images like the H&E (haematoxylin and eosin) images familiar to dermatologists and dermatopathologists.

“This framework can perform virtual histology on a variety of skin conditions, including basal cell carcinoma. It also provides detailed 3D images of several skin layers,” said Ozcan. “In our studies, the virtually stained images showed similar color contrast and spatial features found in traditionally stained microscopic images of biopsied tissue. This approach may allow diagnosticians to see the overall histological features of intact skin without invasive skin biopsies or the time-consuming work of chemical processing and labeling of tissue.”

“The only tool currently used in clinics to help a dermatologist are dermatoscopes, which magnify skin and polarise light. At best, they can help a dermatologist pick up patterns,” said Rubinstein, who also uses reflectance confocal microscopes in clinic.

The authors said there is a way to go before clinical use, but they aim to introduce the technology at various scales alongside other optical-imaging systems. Once the neural network is “trained,” with many tissue samples and the use of powerful graphics processing units (GPUs), it will be able to run on a computer or network, enabling rapid transformation from a standard image to a virtual histology image.

This technology could usher in a new age of “digital dermatology” and change how dermatology is practised. Additionally, the research team will see if this artificial intelligence platform can work with other AI technologies to look for patterns and further aid in clinical diagnosis.

Source: UCLA

The Latest on Gastric Cancer

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November is Gastric Cancer Awareness Month. In 2020, gastric cancer was the sixth most common cancer in 2020, with 1.09 million new cases, according to the World Health Organization.

It was also the fifth most common cause of cancer death in 2020. Gastric cancer is common in certain parts of the world, including South America and Asia. Gastric cancer can affect any part of the stomach, but in most of the world, gastric cancers form in the main part of the stomach.

Mohamad Sonbol, MD, a medical oncologist at Mayo Clinic, shares five things to know about the current state of diagnosis, screening and treatment for gastric cancer:

  • Endoscopy is usually the initial step in diagnosing gastric cancer, allowing physicians to diagnose, stage and treat some cancers at early stages. Using the endoscope, they can go in and remove localised and superficial abnormal growths. If physicians detect gastric cancer, they use a CT and positron emission tomography to scan for further staging.
  • Screening for gastric cancer is not recommended in the general population, unlike in East Asia where it is more common. However, screening protocols are in place for people at higher risk. Risk factors include obesity, smoking, alcohol consumption and family history.
  • Surgery is an option for patients whose cancer has not spread and is surgically removable. Surgery is the only curative approach for patients with localised or locally advanced gastric cancer. Other treatments, such as systemic therapy and radiation, maximise the chance of cure and lower the risk of the cancer returning.
  • New therapeutic options are available for gastric cancer. In the US, the FDA approved the combination of chemotherapy with nivolumab, an immunotherapeutic drug, in metastatic gastric adenocarcinoma. FAM-trastuzumab deruxtecan-NXKI, administered as an infusion, is now an option for patients with HER2-positive metastatic gastric cancer.

Some immunotherapeutics are standard care and some are in studies. Chemotherapy kills cells all over the body, while immunotherapy stimulates the immune system to fight the cancer. Generally, chemotherapy works for a while and then stops. When immunotherapy works, it is usually for a longer time. Which regimen to choose depends on the different targets on the cancer cells.

“I tell patients who have been recently diagnosed with gastric cancer that there is hope,” Dr Sonbol said. “We now have many more treatment options than before.”

Source: EurekAlert!

A Link Between Intestinal Changes, Diet and Disease

A new study published in Nature Metabolism has found a link between diet, intestinal cell changes and disease.

The intestine has to react quickly to changes in nutrition and nutrient balance. One of the ways it does so is with intestinal cells that are specialised in the absorption of food components or the secretion of hormones. In adult humans, the intestinal cells regenerate every five to seven days. The ability to constantly renew and develop all types of intestinal cells from intestinal stem cells is crucial for the natural adaptability of the digestive system. However, a long-term diet high in sugar and fat disrupts this adaptation and can contribute to the development of obesity, type 2 diabetes, and gastrointestinal cancer.

The molecular mechanisms behind this maladaptation are the research area of this study. Intestinal stem cells are thought to play a special role in maladaptation, and to investigate this, the researchers used a mouse model to compare the impacts of a high-sugar and high-fat diet and with a control group.

“The first thing we noticed was that the small intestine increases greatly in size on the high-calorie diet,” said study leader Anika Böttcher. “Together with Fabian Theis’ team of computational biologists at Helmholtz Munich, we then profiled 27 000 intestinal cells from control diet and high fat/high sugar diet-fed mice. Using new machine learning techniques, we thus found that intestinal stem cells divide and differentiate significantly faster in the mice on an unhealthy diet.” The researchers hypothesize that this is due to an upregulation of the relevant signaling pathways, which is associated with an acceleration of tumor growth in many cancers. “This could be an important link: Diet influences metabolic signaling, which leads to excessive growth of intestinal stem cells and ultimately to an increased risk of gastrointestinal cancer,” says Böttcher.

Using this high-resolution technique, the researchers have also been able to study rare cell types in the intestine, such as hormone-secreting cells. Among their findings, they were able to show that an unhealthy diet leads to a reduction in serotonin-producing cells in the intestine. This can result in intestinal inertia (typical of diabetes mellitus) or increased appetite. Furthermore, the absorbing cells were shown to adapt to the high-fat diet, increasing functionality and thus directly contributing to weight gain.

The study findings enable a new understanding of disease mechanisms associated with a high-calorie diet. “What we have found out is of crucial importance for developing alternative non-invasive therapies,” said study leader Heiko Lickert. 

Presently, there is no pharmacological approach to prevent, stop or reverse obesity and diabetes. Only bariatric surgery causes permanent weight loss and can even lead to remission of diabetes. However, these surgeries are invasive, non-reversible and costly to the healthcare system. Novel non-invasive therapies could happen, for example, at the hormonal level through targeted regulation of serotonin levels. This will be an avenue of future research for the group.

Source: EurekAlert!

Leafy Vegetable-rich Diet Could Curb Migraine Symptoms

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It may be worth adopting a plant based diet, rich in dark green leafy vegetables, to ease the symptoms of chronic migraine, suggest doctors reporting on a case study.

Writing in BMJ Case Reports, the doctors’ recommendation comes after treating a man who suffered from migraines for 12 years and had tried medication, yoga and avoiding potential ‘trigger foods’ to no avail.

Over 1 billion people worldwide have migraines, characterised as one-sided, pulsating headaches lasting 4–72 hours, and often accompanied by sensitivity to noise and light and sometimes prodromal auras. While the condition may be treated and prevented with drugs, a growing body of evidence suggests that diet can be an effective treatment.

Six months before his clinic referral, the man’s migraines had become chronic, occurring on 18–24 days of every month. The pain was described as starting suddenly and intensely in the forehead and left temple. The pain was throbbing in nature, usually lasting 72 hours. His headaches were accompanied by sensitivity to light and sound, and nausea and vomiting. On a scale of 0–10, he scored the pain severity as 10–12 out of 10.

Blood tests showed little systemic inflammation and a normal level of beta-carotene (53 µg/dL). This is likely due to his daily sweet potato consumption, which, although high in beta-carotene, are relatively low in the nutrients responsible for the anti-inflammatory and antioxidant properties of carotenoids, the authors pointed out. These are instead found in dark green leafy vegetables, such as spinach. Systemic inflammation and oxidative stress are implicated in migraine.

The authors recommended that he follow the Low Inflammatory Foods Everyday (LIFE) diet, which is a nutrient dense, whole food, plant-based diet.

The LIFE diet includes eating at least five ounces (142g) of dark green leafy vegetables every day, drinking one 32-ounce (905g) daily green LIFE smoothie, and cutting back on whole grains, starchy vegetables, oils, and animal protein, particularly dairy and red meat.

After two months on the LIFE diet, the frequency of his migraine attacks had fallen to just 1 day a month; the length and severity of the attacks had also lessened. Blood tests showed a substantial rise in beta-carotene levels, from 53 µg/dL to 92 µg/dL.

He stopped his migraine meds and even when he tried certain ‘challenge’ foods which triggered headaches, they were less intense. At three months his migraines completely stopped, and they haven’t returned in 7.5 years.
The 60-year-old patient, whose identity was not disclosed, said: “Before I changed my diet, I was suffering six to eight debilitating migraines a month, each lasting up to 72 hours. Most days, I was either having a migraine or recovering from one.”

The man was allergic, which studies suggest contributes to migraines, and his allergies had disappeared. He was also HIV positive, also linked to migraine risk, so it is certainly possible that the man’s HIV status and antiretroviral drugs had contributed to his symptoms, the reports acknowledge, which they could not exclude.
Nevertheless they concluded: “This report suggests that a whole food plant-based diet may offer a safe, effective and permanent treatment for reversing chronic migraine.

“While this report describes one very adherent patient who had a remarkable response, the LIFE diet has reduced migraine frequency within three months in several additional patients (personal communication).”

Source: EurekAlert!

Extreme Heat Threatens Cardiovascular Health

Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash


With South Africa’s summer being expected to be both wetter and hotter this year, there is a greater risk of adverse cardiovascular incidents, especially for adults with pre-existing cardiovascular diseases. Experts writing in the Canadian Journal of Cardiology discuss how extreme heat affects cardiovascular health, why health professionals should care and what recommendations they can make to minimise consequences.

Extreme heat events are predicted to become longer, more common and more severe. Some 70 000 heat-related deaths occurred during the 2003 European heatwave. Risk factors for heat-related hospitalisation include age, chronic illnesses, social isolation, some medications, and lack of access to air conditioning. Among chronic illnesses, cardiovascular diseases are often identified as a risk factor for heat-related hospitalisation and death.

The Intergovernmental Panel on Climate Change (IPCC) recently reported that global temperatures are rising at a greater rate than previously projected, and that the number of extreme heat days will significantly increase across most land regions,” said senior author Daniel Gagnon, PhD, University of Montreal. “Although we don’t yet fully understand the reasons, people with cardiovascular disease are at greater risk of hospitalisations and death during extreme heat events.”

The researchers reviewed studies and noted a consistent association between extreme heat and increased risk of adverse cardiovascular outcomes. An examination of reviews and meta-analyses on the effect of extreme heat on adverse cardiovascular outcomes showed that heatwaves significantly increase mortality risk from ischaemic heart disease, stroke, and heart failure.

“Although the effects of extreme heat on adverse cardiovascular events have been explained in the context of heatstroke, many events occur without heatstroke, and the mechanisms of these events in the absence of heatstroke remain unclear,” observed Dr Gagnon. “It is likely that heat exposure increases myocardial oxygen needs.”

One possibility is that heat exposure puts excessive strain on the heart for individuals with heart disease and that heat exposure increases the risk of blood clots forming within cardiac blood vessels.

The authors propose that preventive strategies should aim to reduce the extent of hyperthermia and dehydration. In Canada, heat-health warnings systems act as a first line of defence by raising awareness of upcoming heat events and recommending strategies to minimise possible heat complications. For example, heat warnings are issued 18-24 hours before a heat event in Ontario and Québec, when ambient temperature will remain above 30°C for a minimum of two days. Public advisories include identifying the signs of heat stress, ensuring people drink adequate amounts of cold fluid or seeking an air-conditioned environment – though for many people, this is not an option.

Recent research supports electric fan use, skin wetting and immersing the feet in tap water as simple methods to stay cool during extreme heat events. “Air conditioning is the most effective strategy that can be recommended since it effectively removes the heat stimulus and minimises the risk of adverse cardiovascular outcomes,” commented Dr Gagnon. “However, less than one third of global households own air conditioning.”

More studies are needed to explain why extreme heat is linked to increased risk of adverse cardiovascular outcomes; the effect of cardiovascular medication on the human body’s physiological responses during heat exposure; the best cooling strategies in heat waves for individuals with CVD; and safe environmental limits for outdoor exercise in individuals with heart disease.

“Cardiovascular health professionals need to be aware of the negative consequences of extreme heat on cardiovascular health. A better awareness and understanding of the cardiovascular consequences of extreme heat, and of the measures to take to prevent and mitigate adverse events, will help us all assess the risk and optimize the care of patients exposed to an increasingly warm climate,” concluded Dr Gagnon.

Source: Elsevier