Three decades-old antibiotics could offer an alternative to opioid-based painkillers

Three decades-old antibiotics administered together can block a type of pain triggered by nerve damage in an animal model, UT Southwestern researchers report. The finding, published online today in PNAS, could offer an alternative to opioid-based painkillers, addictive prescription medications that are responsible for an epidemic of abuse in the U.S.

Over 100 million Americans are affected by chronic pain, and a quarter of these experience pain on a daily basis, a burden that costs an estimated $600 billion in lost wages and medical expenses each year. For many of these patients – those with cancer, diabetes, or trauma, for example – their pain is neuropathic, meaning it's caused by damage to pain-sensing nerves.

To treat chronic pain, prescriptions for opioid painkillers have increased exponentially since the late 1990s, leading to a rise in abuse and overdoses. Despite the desperate need for safer pain medications, development of a new prescription drug typically takes over a decade and more than $2 billion according to a study by the Tufts Center for the Study of Drug Development, explains study leader Enas S. Kandil, M.D., associate professor of anesthesiology and pain management at UTSW.

Seeking an alternative to opioids, Kandil and her UT Southwestern colleagues – including Hesham A. Sadek, M.D., Ph.D., professor of internal medicine, molecular biology, and biophysics; Mark Henkemeyer, Ph.D., professor of neuroscience; Mahmoud S. Ahmed, Ph.D., instructor of internal medicine; and Ping Wang, Ph.D., a postdoctoral researcher – explored the potential of drugs already approved by the Food and Drug Administration (FDA).

The team focused on EphB1, a protein found on the surface of nerve cells, which Henkemeyer and his colleagues discovered during his postdoctoral training nearly three decades ago. Research has shown that this protein is key for producing neuropathic pain. Mice genetically altered to remove all EphB1 don't feel neuropathic pain, he explains. Even mice with half the usual amount of this protein are resistant to neuropathic pain, suggesting EphB1's promise as a target for pain-relieving drugs. Unfortunately, no known drugs inactivate EphB1.

Exploring this angle further, Ahmed used computer modeling to scan a library of FDA-approved drugs, testing if their molecular structures had the right shape and chemistry to bind to EphB1. Their search turned up three tetracyclines, members of a family of antibiotics used since the 1970s. These drugs – demeclocycline, chlortetracycline, and minocycline – have a long history of safe use and minimal side effects, Ahmed says.

To investigate whether these drugs could bind to and inactivate EphB1, the team combined the protein and these drugs in petri dishes and measured EphB1's activity. Sure enough, each of these drugs inhibited the protein at relatively low doses. Using X-ray crystallography, Wang imaged the structure of EphB1 with chlortetracycline, showing that the drug fits neatly into a pocket in the protein's catalytic domain, a key portion necessary for EphB1 to function.

In three different mouse models of neuropathic pain, injections of these three drugs in combination significantly blunted reactions to painful stimuli such as heat or pressure, with the triplet achieving a greater effect at lower doses than each drug individually. When the researchers examined the brains and spinal cords of these animals, they confirmed that EphB1 on the cells of these tissues had been inactivated, the probable cause for their pain resistance. A combination of these drugs might be able to blunt pain in humans too, the next stage for this research, says Kandil.

Unless we find alternatives to opioids for chronic pain, we will continue to see a spiral in the opioid epidemic. This study shows what can happen if you bring together scientists and physicians with different experience from different backgrounds. We're opening the window to something new."

Enas S. Kandil, M.D., Associate Professor, Anesthesiology and Pain Management, UT Southwestern

Source:

UT Southwestern Medical Center

Posted in: Medical Science News | Medical Research News | Pharmaceutical News

Tags: Anesthesiology, Animal Model, Antibiotic, Cancer, Cardiology, Chronic, Chronic Pain, Crystallography, Diabetes, Drugs, Education, heat, Medicine, Minocycline, Molecular Biology, Nerve, Neuropathic Pain, Neuroscience, Opioids, Pain, Pain Management, pH, Prescription Drug, Protein, Receptor, Research, Tetracycline, Trauma, X-Ray

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Diabetes symptoms: Five ‘unusual’ signs of high blood sugar you shouldn’t ignore

Diabetes expert reveals rise of cases in children during pandemic

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Diabetes affects around five million people in the UK, and 90 percent of those cases are caused by type 2 diabetes. But it can be really difficult to know if you’re at risk of the condition. These are the subtle symptoms you should be watching out for.

Diabetes is a common condition that’s caused by the body struggling to convert sugar in the blood into useable energy.

Having diabetes increases your risk of developing some serious medical conditions, including heart disease and strokes.

If you develop any of the key warning signs of diabetes, you should speak to a doctor straight away.

Aside from the more common symptoms, there are a number of “unusual” signs to look out for, according to medical website Healthline.

Breath scent

Some diabetes patients may find that their breath develops a fruity scent.

The smell is caused by diabetic ketoacidosis; a complication of high blood sugar.

In the absence of insulin, the body starts to break down fat cells for energy. But this process produces an acid – known as ketones – as a by-product.

If you have diabetes, you may find that your breath smells of fruit or nail polish.

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Itchiness

Persistent itching is a lesser-known symptom of diabetes, and it’s caused by nerve damage.

High blood sugar has a direct impact on the nerve fibres in the body – and not in a good way.

The nerve damage usually impacts the hands and feet, but it can actually develop anywhere on the body.

As a result, the body’s natural reaction is to start itching in the areas with nerve damage.

Dry mouth

High blood sugar can reduce saliva flow in the mouth, warned the medical website.

While it’s normal to occasionally have a dry mouth, you should speak to a doctor if it continues to happen, for no obvious reason.

Erectile dysfunction

Type 2 diabetes patients may develop some kind of sexual dysfunction, including impotence.

It’s caused by high blood sugar damaging the blood vessels that carry blood to the penis.

Dark skin patches

Some diabetes patients may find that they develop dark, velvety patches of skin.

These patches can be widespread across the body, or in just certain folds of the skin.

It’s a condition known as acanthosis nigricans, and it’s most common around the neck.

The patches develop as high levels of insulin in the blood can cause skin cells to reproduce faster than normal.

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Metabolomics and machine learning used to identify possible COVID-19 biomarkers

One of the many mysteries still surrounding COVID-19 is why some people experience only mild, flu-like symptoms, whereas others suffer life-threatening respiratory problems, vascular dysfunction and tissue damage.

Now, researchers reporting in ACS' Analytical Chemistry have used a combination of metabolomics and machine learning to identify possible biomarkers that could both help diagnose COVID-19 and assess the risk of developing severe illness.

Although some pre-existing conditions, such as diabetes or obesity, can increase the risk of hospitalization and death from COVID-19, some otherwise healthy people have also experienced severe symptoms. As most of the world's population awaits vaccination, the ability to simultaneously diagnose a patient and estimate their risk level could allow better medical decision-making, such as how closely to monitor a particular patient or where to allocate resources.

Therefore, Anderson Rocha, Rodrigo Ramos Catharino and colleagues wanted to use mass spectrometry combined with an artificial intelligence technique called machine learning to identify a panel of metabolites that could do just that.

The cross-sectional study included 442 patients who had different severities of COVID-19 symptoms and tested positive by a reverse transcriptase-polymerase chain reaction (RT-PCR) test, 350 controls who tested negative for COVID-19 and 23 people who were suspected of having the virus despite a negative RT-PCR test.

The researchers analyzed blood plasma samples from the participants with mass spectrometry and machine learning algorithms, identifying 19 potential biomarkers for COVID-19 diagnosis and 26 biomarkers that differed between mild and severe illnesses. Of the COVID-19-suspected patients, 78.3% tested positive with the new approach, possibly indicating these were RT-PCR false negatives.

Although the identified biomarkers, which included metabolites involved in viral recognition, inflammation, lipid remodeling and cholesterol homeostasis, need to be further verified, they could reveal new clues to how SARS-CoV-2 affects the body and causes severe illness, the researchers say.

Source:

American Chemical Society

Journal reference:

Delafiori, J., et al. (2021) Covid-19 Automated Diagnosis and Risk Assessment through Metabolomics and Machine Learning. Analytical Chemistry. doi.org/10.1021/acs.analchem.0c04497.

Posted in: Biochemistry

Tags: Analytical Chemistry, Artificial Intelligence, Blood, Cholesterol, Diabetes, Education, Flu, Inflammation, Machine Learning, Mass Spectrometry, Metabolites, Metabolomics, Obesity, Polymerase, Polymerase Chain Reaction, Research, Respiratory, Reverse Transcriptase, SARS, SARS-CoV-2, Spectrometry, Vascular, Virus

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Immune response to insulin could identify, help treat those at risk for type 1 diabetes

diabetes

Researchers from the Barbara Davis Center for Childhood Diabetes at the University of Colorado Anschutz Medical Campus have found that immune responses to insulin could help identify individuals most at risk for developing Type 1 diabetes.

The study, out recently in the Proceedings of the National Academy of Sciences, measured immune responses from individuals genetically predisposed to developing Type 1 diabetes (T1D) to naturally occurring insulin and hybrid insulin peptides. Since not all genetically predisposed individuals develop T1D, researchers sought to examine T-cell immune responses from the peripheral blood that could occur before the onset of clinical diabetes.

“We want to know why people develop T1D, and this research has helped provide a lot more information and data as to what it looks like when genetically at-risk individuals are headed towards clinical diagnosis,” says Aaron Michels, MD, the study’s lead researcher, Associate Professor of Medicine at CU Anschutz and researcher at the Barbara Davis Center. “Ideally, you want to treat a disease when it’s active, so this is a need in our field to understand when people have an immune response directed against insulin producing cells.”

Researchers collected blood samples from genetically at-risk adolescents every 6 months for two years. Inflammatory T-cell responses to hybrid insulin peptides correlated with worsening blood glucose measurements and progression to T1D development. The results indicate an important advancement in identifying the risk of T1D early as well as the potential for intervention.

“There are now therapies used in research studies that have delayed the onset of clinical type 1 diabetes,” says Michels. “Patients with these specific immune responses, may benefit from immune intervention to delay T1D onset and possibly prevent it for years.”

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What is high cholesterol?

What is cholesterol?

Cholesterol (ko-LES-ter-ol) is a fatty substance found in the body. (1) It moves around the body in the blood by attaching itself to proteins, creating molecules known as lipoproteins. (2)

Types of cholesterol

There are two types of cholesterol: low-density lipoprotein (LDL) and high-density lipoprotein (HDL).

These types are often labelled as good and bad respectively. (3) LDL is considered to be harmful to the body; whereas HDL is considered to be protective. (2)

This is because too much LDL can lead to a build-up in the arteries; whereas excess HDL is broken down and removed from the body. (3)

Where is cholesterol found?

Cholesterol is produced by the liver, but it is also found in some foods. (3)

Foods that are particularly high in cholesterol include:

  • Kidneys and other offal
  • Eggs
  • Prawns
  • Full fat dairy products
  • Meats (4, 5, 6)

Despite cholesterol being found in some foods; it is important to remember that a lot of the cholesterol found in the body actually comes from foods that are high in saturated fat. This is because this fat is turned into cholesterol by the liver. (6)

What does cholesterol do in the body?

The two types of cholesterol do different things in the body. LDL carries cholesterol from the liver to cells that require it; whereas HDL carries cholesterol in the opposite direction – from the cells to the liver. (3)

Cholesterol is also used in the body to make some hormones, vitamin D and some substances that aid digestion. (1)

Specifically, cholesterol is used to make the stress hormones. These are also known as adrenal corticoid hormones and include cortisol, corticosterone and so forth. Cholesterol is also used to make sex hormones: androgens and estrogens. (16)

Cholesterol is used in the making of bile acids, which aid the digestion of food – particularly the digestion of fats. Cholesterol in the bile acid is reabsorped into the intestinal tract once it has been used to break down the fats. Thus, one way of lowering cholesterol levels is to target this reabsorption. (16)

Overall, it is important that your body has cholesterol as these things are essential for the body to function. For example, hormones carry signals around the body. (6)

High cholesterol

Despite cholesterol being important for the body to function, too much cholesterol can be a bad thing.

Video following the life of a man recently diagnosed with high cholesterol. Source: British Heart Foundation

But how high do cholesterol levels have to be to be considered dangerous?

According to the NHS, the UK government states that healthy cholesterol levels are defined as total cholesterol levels below 5mmol/L and LDL levels below 3mmol/L. (7)

The BBC, however, states that healthy cholesterol levels are controversial. (6)

Both the NHS and the BBC stress that healthy levels for people with (or at high risk of) heart disease, hypertension or diabetes should be lower. Specifically they recommend that these high risk individuals should keep their cholesterol levels below 4mmol/L and their LDL levels below 2mmol/L. (6, 7)

How can you tell if you have high cholesterol?

There are not many symptoms of high cholesterol; consequently it may be hard to tell that you have high cholesterol. (8)

One symptom that you may find is yellow patches, called xanthomas, on your skin. These particularly affect the skin around the eye area. (9)

Xanthomas can, however, be caused by other problems, such as diabetes, primary biliary cirrhosis and some cancers. (10)

The main way to tell whether you have high cholesterol is to have a blood test. This may involve fasting for 10-12 hours before the test, to make sure your food does not influence the test. (7)

The blood may be taken either using a needle or syringe or by pricking your finger. (9)

What causes high cholesterol?

The three main things that affect your cholesterol levels are diet, weight and level of physical activity.

If your diet is high in saturated fat, then your blood cholesterol levels will be higher. Similarly, if you are overweight then you are also at a higher risk of high cholesterol.

Physical activity levels can also contribute to your cholesterol levels. Being active for 30 minutes most days can help lower bad cholesterol and raise good cholesterol. (11)

Despite eating a healthy diet, some people may still have high cholesterol. This may be something that they have inherited. There is a condition called familial hyperlipidaemia which is inherited and causes high cholesterol. (2)

What diseases does high cholesterol cause?

High cholesterol makes you more likely to get coronary heart disease. (1)

This is because the LDL can build up inside the coronary arteries, this makes the arteries become narrower. The narrowing of arteries is also known as atherosclerosis. (3)

Atherosclerosis means that blood clots can more easily block the arteries. This can lead to heart attacks. (8)

LDL can also build up in other arteries, such as those that lead to the brain. This can lead to stroke. (1)

High cholesterol can also lead to something that is called a mini-stroke. This is also known as a transient ischaemic attack (TIA). A mini-stroke has similar symptoms to a stroke and is caused by a temporary reduction in the blood supply to the brain. This can be caused by atherosclerosis. (3, 12, 13)

What treatments are there for high cholesterol?

There are several ways that you can lower your cholesterol levels: through a healthy diet; exercising more and taking medications.

Healthy diet

A healthy diet involves lowering your intake of saturated fats, such as:

  • Fatty meats
  • Meat pies
  • Butter
  • Cream
  • Cakes and biscuits (2, 4)

The Food Standards Agency recommends that men and women eat no more than 30g and 20g of saturated fat per day respectively. (14)

It also involves eating more healthy foods like:

  • Oily fish, such as mackerel and salmon
  • High-fibre foods such as beans, pulses and lentils
  • Fruit and vegetables
  • Garlic, cooked or raw
  • Foods that contain antioxidants and vitamins C and E, such as strawberries, broccoli and so forth (2, 4, 11)

Exercise

The NHS recommends that you do 150 minutes of moderate-intensity aerobic activity every week. They define this activity as exercise that makes your heart beat faster and causes you to break into a sweat; yet still allows you to be able to talk whilst working. (4)

Medications to lower cholesterol

Some people may need to take medications to lower their cholesterol. Whether this is deemed necessary depends on your LDL and HDL levels, along with your risk of cardiovascular disease. (2)

Video following a man who decides to take statins to lower his cholesterol levels. Source: British Heart Foundation

There are several different medications available to lower cholesterol; these include statins, aspirin, niacin and so forth. (14)

Statins are perhaps the most well-known medicines used to lower cholesterol. They are in fact a group of medicines that include simvastatin, atorvastatin, fluvastatin, pravastatin and rosuvastatin. (9)

They work by blocking an enzyme in your liver that helps make cholesterol.

They can, however, cause side effects including muscle pain and stomach problems, such as indigestion. (9, 14)

Aspirin may be prescribed to prevent blood clots from forming.

Niacin may also be given to lower cholesterol. This is because in high doses it can lower LDL and increase HDL.

Yet again there are potential side effects with this drug. It can lead to liver damage if taken for long periods of time. Also it may cause flushing, which is where the face turns red.

In order to reduce these side effects, it is recommended that you do not take too many niacin supplements and instead try to get as much niacin as you can though your diet. (14)

Several foods contain niacin, which is also known as vitamin B3. These include:

  • Beef, pork and generally foods that are high in protein
  • Fish
  • Some nuts, including peanuts
  • Whole grains (15)

Sources

  1. http://www.nhlbi.nih.gov/health/health-topics/topics/hbc/
  2. http://www.bhf.org.uk/heart-health/conditions/high-cholesterol.aspx
  3. http://www.nhs.uk/conditions/Cholesterol/Pages/Introduction.aspx
  4. http://www.nhs.uk/Livewell/Healthyhearts/Pages/Cholesterol.aspx
  5. www.betterhealth.vic.gov.au/…/Cholesterol_explained
  6. www.bbc.co.uk/health/physical_health/conditions/cholesterol1.shtml
  7. http://www.nhs.uk/Conditions/Cholesterol/Pages/Diagnosis.aspx
  8. http://www.cdc.gov/cholesterol/faqs.htm
  9. www.bupa.co.uk/…/high-cholesterol
  10. http://www.nlm.nih.gov/medlineplus/ency/article/001447.htm
  11. http://www.indstate.edu/humres/docs/high_cholesterol.pdf
  12. www.nhs.uk/…/Introduction.aspx
  13. www.nhs.uk/Conditions/Transient-ischaemic-attack/Pages/Causes.aspx
  14. http://www.nhs.uk/Conditions/Cholesterol/Pages/Treatment.aspx
  15. http://www.moh.gov.my/images/gallery/rni/8_chat.pdf
  16. http://www.mendedhearts.org/Docs/HB-Fall04-Cholesterol.pdf

Further Reading

  • All Cholesterol Content
  • Cholesterol – What is Cholesterol?
  • Cholesterol Physiology
  • Hypercholesterolemia and Hypocholesterolemia
  • High Cholesterol and Stroke Risk
More…

Last Updated: Apr 19, 2019

Written by

April Cashin-Garbutt

April graduated with a first-class honours degree in Natural Sciences from Pembroke College, University of Cambridge. During her time as Editor-in-Chief, News-Medical (2012-2017), she kickstarted the content production process and helped to grow the website readership to over 60 million visitors per year. Through interviewing global thought leaders in medicine and life sciences, including Nobel laureates, April developed a passion for neuroscience and now works at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour, located within UCL.

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What is Autoimmunity?

The term autoimmunity refers to a failure of the body’s immune system to recognize its own cells and tissues as “self”. Instead, immune responses are launched against these cells and tissues as if they were foreign or invading bodies.

The immune system exists in almost all complex life forms. The main functions of the immune system are to defend the body from germs and other foreign invaders. The immune system is composed of special cells and organs that together mount an immune attack against foreign chemicals, viruses, bacteria, or pollen.

A cell called a B lymphocyte develops into a plasma cell, which produces antibodies to fight off such invaders. Any such substance that triggers an immune response in this way is referred to as an antigen. For the immune system to function appropriately, it must be able to distinguish cells that are “self” form substances that are non-self or foreign. Autoimmunity refers to when the immune system fails to do this and instead produces antibodies that are directed towards the body’s own tissues. These are called auto-antibodies.

Some of the main examples of autoimmune disorders include diabetes mellitus type 1 (IDDM), systemic lupus erythematosus (SLE), Hashimoto's thyroiditis, Graves' disease of the thyroid, Sjögren's syndrome, Churg-Strauss Syndrome, Coeliac disease, rheumatoid arthritis (RA), and idiopathic thrombocytopenic purpura.

In previous years, a misconception existed that the body was not capable of recognising “self” antigens. At the start of the twentieth century, Paul Ehrlich described the concept of “horror autotoxicus,” which referred to how a normal body would not create an immune attack against its own tissue. Therefore, such responses were considered abnormal and a sign of disease. Now, however, we know that autoimmunity is a key part of the vertebrate immune system, but that it is usually kept in check by an immunological tolerance of antigens that are “self.”

Sources

  1. www.oucom.ohiou.edu/…/Lecture17_autoimmunity2xpg.pdf
  2. www.kau.edu.sa/…/…_7_AUTOIMMUNITY_AND_AUTOIMMUNE_DISEASE_Part1.pdf
  3. omicsonline.org/…r-basis-in-todays-perspective-2155-9899.S10-003.pdf
  4. www.st-andrews.ac.uk/~gdk/bl4217web/Gp2RefList/autoimmune_path.pdf
  5. http://www.kims.org.kw/bulletin/Issues/Issue9/Autoimmunity_I.PDF

Further Reading

  • All Autoimmunity Content
  • Low-Level Autoimmunity
  • Autoimmunity Immunological Tolerance
  • Autoimmunity Genetic Factors
  • Autoimmunity Sex
More…

Last Updated: Aug 23, 2018

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.

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What is a Vitrectomy?

A vitrectomy is a surgical procedure that may be carried out for a number of reasons:

  • improving vision in patients experiencing complications from diabetes
  • removing foreign bodies from the eye in cases of trauma
  • taking a biopsy to diagnose infections or diseases
  • as part of other operative procedures on the retina

The aim of the procedure in most cases is to remove the vitreous humour to allow access to other parts of the eye.

The vitreous humour is usually a transparent, gelatinous substance inside the eye, found behind the iris and the lens, and in front of the retina. Its only purpose is to give volume to the eye.

There are two different types of vitrectomies, posterior pars plana vitrectomy and anterior vitrectomy.

Posterior pars plana vitrectomy

This type of vitrectomy is carried out by a retina specialist. This procedure involves removing the vitreous gel from the eye through the pars plana, the region of the eye that is thought to have no function in the post-fetal period and as such is thought to be the safest point of entry into the eye. Surgical instruments are also introduced into the eye through the pars plana.

The vitreous jelly is dissected and then peeled or sucked out through small 1mm cuts made into the white of the eye. Any necessary repairs to the retina are carried out, as well as removing any foreign bodies, or, in the case of surgery to treat complications of diabetes, leaking blood vessels are sealed.

Image Credit: Saginbay / Shutterstock

Anterior vitrectomy

Anterior vitrectomies are carried out when vitreous gel leaks through the pupil and into the anterior (front) chamber of the eye. Eye trauma, cataracts of the lens, and corneal or glaucoma surgery, can cause this to occur. Anterior vitrectomies aim to minimize the risk of developing future problems due to leaking vitreous fluid, and to improve visual recovery.

Vitrectomy procedure: steps

Before the vitrectomy is done, pre-operative assessments are carried out. A full history is taken, covering both general and eye health, and details of medications prescribed for other conditions are discussed. Checks to ensure that anesthesia may be safely used on the individual patient will also be carried out. General anesthesia is usually used for vitrectomy procedures, but local anaesthetic can also be used if precisely placed.

Once a patient is underneath anesthesia, the eye is kept open with forceps. The doctor will make a small (1mm) incision, and cut through the pars plana, also known as the sclera or the white of the eye. A surgical microscope that allows a wide view of the inside of the eye, along with a magnified view, is inserted. Fiberoptic cables are also used to illuminate the inside of the eye. These instruments are inserted via separate openings. The vitreous fluid is then extracted using a vitrectomy probe and any retinal problems are treated at the same time. In diabetics, leaking blood vessels are laser-coagulated at this time.

The procedure usually takes several hours.

As vitreous jelly does not reform by itself, it is necessary to replace it with one of the substances below:

  • A gas bubble that is absorbed naturally over 2-3 weeks
  • Air that is absorbed within 24-36 hours
  • A blend of gas and air
  • An oil or heavy liquid that is surgically removed later

The chamber that was once filled with vitreous jelly will be filled naturally with aqueous humour after the gas and air have been absorbed.

Recovery from vitrectomy surgery

After vitrectomy surgery, vision will be blurred for several weeks. The eye will be sensitive and swollen, and improvement may not be seen until two weeks after the surgery.

If gas or oil has been used to replace the vitreous jelly, some patients are told to position their head in a downward tilt to ensure that the gas or oil is against the treated area of the retina, as gas will float to the top of the eye. Patients are asked to do this for around 4 to 14 days, for 50 minutes per hour, although this can change depending on the reason for the surgery. To make this more comfortable, neck pillows can be used. It is also advised that patients lie on their front when sleeping. All of these measures help the retina to heal in the right place.

Complications from vitrectomy procedures

Cataracts are known to occur after vitrectomies. The formation of cataracts has been linked to high oxygen levels in the proximity of the lens, which isn’t usually exposed to a lot of oxygen. It is hypothesized that the substances used to replace vitreous fluid do not keep oxygen away from the lens as efficiently as the natural vitreous fluid does. Retinal damage can also occur when air is inserted into the eye to replace the vitreous fluid.

If patients experience a significant decrease in vision quality, or increase in colored discharge, pain, swelling, light sensitivity or redness, emergency medical attention from an eye hospital should be sought.

Some patients may experience high pressure in the eye, which is treated with eye drops. Increased pressure in the eye can cause double vision and pain.

There is also a risk of infection, as with any surgical procedure. Infections will usually be treated with antibiotics.

Other complications include:

  • Bleeding in the eye
  • Damage to the lens
  • Problems with eye movement
  • Inflammation
  • Retinal re-detachment
  • Drooping eyelid
  • Distorted or blurred vision

Sources

  • https://www.asrs.org/patients/retinal-diseases/25/vitrectomy
  • www.ouh.nhs.uk/patient-guide/leaflets/files/100322vitrectomy.pdf
  • www.guysandstthomas.nhs.uk/…/vitrectomy.pdf
  • www.reviewofophthalmology.com/…/complications-of-vitreoretinal-surgery

Further Reading

  • All Vitrectomy Content

Last Updated: Feb 26, 2019

Written by

Lois Zoppi

Lois is a freelance copywriter based in the UK. She graduated from the University of Sussex with a BA in Media Practice, having specialized in screenwriting. She maintains a focus on anxiety disorders and depression and aims to explore other areas of mental health including dissociative disorders such as maladaptive daydreaming.

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Metformin use reduces risk of death for patients with COVID-19 and diabetes

metformin

Use of the diabetes drug metformin—before a diagnosis of COVID-19—is associated with a threefold decrease in mortality in COVID-19 patients with Type 2 diabetes, according to a racially diverse study at the University of Alabama at Birmingham. Diabetes is a significant comorbidity for COVID-19.

“This beneficial effect remained, even after correcting for age, sex, race, obesity, and hypertension or chronic kidney disease and heart failure,” said Anath Shalev, M.D., director of UAB’s Comprehensive Diabetes Center and leader of the study.

“Since similar results have now been obtained in different populations from around the world—including China, France and a UnitedHealthcare analysis—this suggests that the observed reduction in mortality risk associated with metformin use in subjects with Type 2 diabetes and COVID-19 might be generalizable,” Shalev said.

How metformin improves prognosis in the context of COVID-19 is not known, Shalev says. The UAB findings suggest that the mechanisms may go beyond any expected improvement in glycemic control or obesity, since neither body mass index, blood glucose nor hemoglobin A1C were lower in the metformin users who survived as compared to those who died.

“The mechanisms may involve metformin’s previously described anti-inflammatory and anti-thrombotic effects,” Shalev said.

The study—first made available in MedRxiv and now published in the peer-reviewed journal Frontiers in Endocrinology—included 25,326 patients tested for COVID-19 at the tertiary care UAB Hospital between Feb. 25 and June 22 of last year. Of the 604 patients found to be COVID-19-positive, 311 were African Americans.

The primary outcome in the study was mortality in COVID-19-positive subjects, and the potential association with subject characteristics or comorbidities was analyzed.

Researchers found that Blacks, who are only 26 percent of Alabama’s population, were 52 percent of those who tested positive for COVID-19, and only 30 percent of those who tested negative. In contrast, only 36 percent of the COVID-19-positive subjects were white, while whites made up 56 percent of those who tested negative, further underlining the racial disparity. Once COVID-19-positive though, no significant racial difference in mortality was observed.

“In our cohort,” Shalev said, “being African American appeared to be primarily a risk factor for contracting COVID-19, rather than for mortality. This suggests that any racial disparity observed is likely due to exposure risk and external socioeconomic factors, including access to proper health care.”

Overall mortality for COVID-19-positive patients was 11 percent. The study found that 93 percent of deaths occurred in subjects over the age of 50, and being male or having high blood pressure was associated with a significantly elevated risk of death. Diabetes was associated with a dramatic increase in mortality, with an odds ratio of 3.62. Overall, 67 percent of deaths in the study occurred in subjects with diabetes.

The researchers looked at the effects of diabetes treatment on adverse COVID-19 outcomes, focusing on insulin and metformin as the two most common medications for Type 2 diabetes. They found that prior insulin use did not affect mortality risk.

However, prior metformin use was a different matter. Metformin use significantly reduced the odds of dying, and the 11 percent mortality for metformin users was not only comparable to that of the general COVID-19-positive population, it was dramatically lower than the 23 percent mortality for diabetes patients not on metformin.

After controlling for other covariates, age, sex and metformin use emerged as independent factors affecting COVID-19-related mortality. Interestingly, even after controlling for all these other covariates, death was significantly less likely—with an odds ratio of 0.33—for Type 2 diabetes subjects taking metformin, compared with those who did not take metformin.

“These results suggest that, while diabetes is an independent risk factor for COVID-19-related mortality,” Shalev said, “this risk is dramatically reduced in subjects taking metformin—raising the possibility that metformin may provide a protective approach in this high-risk population.”

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Levels of diabetes have tripled in 25 years

The proportion of adults with diagnosed diabetes trebled between 1994 and 2019, report researchers from UCL and the National Center for Social Research (NatCen), who have analyzed the latest results from the Health Survey for England (HSE).

The report, which is commisisoned by NHS Digital, analyzes data from over 8,200 adults and 2,000 children living in private households in England and shows the percentage of people who have been diagnosed with diabetes has risen since 1994, from 3% to 9% among men and from 2% to 6% among women.

The researchers found that total diabetes (which includes both diagnosed cases and people found by the survey to have undiagnosed diabetes) is much more common among people with lower incomes and also among those with obesity. For example, 16% of people in the lowest income group had diabetes but only 7% in the highest income group. The proportion of adults with total diabetes increased from 5% of those with normal weight to 9% of adults with overweight and 15% of adults with obesity.

Additionally, the report highlights that adults living in the most deprived areas are the most likely to be obese. This difference was particularly pronounced for women, where 39% of women in the most deprived areas were obese, compared with 22% in the least deprived areas. The survey also found that children’s obesity was closely associated with whether their parents’ were overweight or obese.

Professor Jennifer Mindell, co-editor of the report, (UCL Research Department of Epidemiology and Public Health) said: “Over the past few decades, diabetes has become more common in both high and low income countries. We have known for a long time that diabetes increases the risks of developing circulatory diseases and cancers.

“We have seen this year that it also increases the risks of serious infection and death in people infected with COVID-19. Diabetes is much more common in people with obesity. The COVID-19 pandemic has rightly prompted greater focus on obesity reduction, which will also help with the problem of rising diabetes.”

For the first time, the survey also asked about GP consultations. It shows that 69% of men and 82% of women had consulted a GP in the previous 12 months. GP consultations are more common in older ages, especially among men, and also increase with Body Mass Index (BMI): 80% of adults with obesity reported having a GP consultation in the last year, compared with 74% of overweight and normal weight adults.

84% of respondents said they had consulted their GP solely for a physical health problem, 5% for a mental health, nervous or emotional problem and 11% for both types of problem in the last 12 months. Women were more likely than men to have discussed a mental health problem with their GP and to use counseling or therapy services for a mental health problem.

The report finds that consultations for mental health problems were more common among those from lower incomes: 25% of adults in the lowest income group had a consultation about a mental health problem in the last year, compared with 15% of adults in the highest income group.

Additional reports on HSE 2019 include findings on adult health behaviors, carers and eating disorders.

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DR MICHAEL MOSLEY: Why won't the NHS tell you how to treat diabetes?

DR MICHAEL MOSLEY: Why won’t the NHS tell you the secret to treating diabetes? (Clue: It costs nothing)

Eight years ago I managed to beat type 2 diabetes by going on my 5:2 diet (cutting my calories two days a week) and losing weight — 9kg to be precise. 

Since then I’ve become something of a broken record on the importance of shedding body fat to improve your blood sugar levels.

So I was delighted last week by the news from the Norfolk Diabetes Prevention Study — the largest of its kind in the world — which showed that even modest weight loss can have a big impact.

A recent review by Danish researchers found more than 70 per cent of people with type 2 diabetes who had lost significant amounts of weight were still medication-free more than five years later [File photo]

The Norfolk study recruited more than 1,000 people with pre-diabetes (meaning they had raised blood sugar levels). They were asked to lose weight, then were monitored for more than eight years. Those who managed to lose 2kg to 3kg, and keep it off, almost halved their risk of developing full-blown type 2.

This adds to extensive research carried out by British scientists showing that, as well as pre-diabetes, type 2 diabetes can be put into remission by going on a rapid weight-loss diet. And, as we’ve known for 20 years, weight-loss surgery can also reverse type 2.

In fact, a recent review by Danish researchers found more than 70 per cent of people with type 2 diabetes who had lost significant amounts of weight were still medication-free more than five years later.

Despite all this, the NHS Choices website still tells you type 2 diabetes is a ‘progressive’ disease that ‘usually gets worse over time’, with most people needing ever increasing levels of medication. What a depressing — and I would argue inaccurate — message.

So why aren’t they being a bit more encouraging? The situation with type 2 diabetes reminds me of a tussle I had with the medical establishment more than 25 years ago. 

In 1993 I was looking around for a subject to make a science documentary, when I came across the work of two Australians, Dr Barry Marshall and Dr Robin Warren, who had a striking new theory about stomach ulcers.

I was delighted last week by the news from the Norfolk Diabetes Prevention Study — the largest of its kind in the world — which showed that even modest weight loss can have a big impact [File photo]

At the time, stomach or duodenal ulcers (affecting the first part of the small intestine) were incredibly common but, like type 2, were seen as something of a mystery.

Gut ulcers can be excruciatingly painful and lead to internal bleeding. Doctors knew they were caused by excess acid and they could be managed by drugs such as ranitidine, which stopped the stomach from producing acid. These drugs, known as proton pump inhibitors, were expensive but there was a lot of incentive to use them because if you didn’t, or if the drugs stopped working, there was a high chance you’d need some of your stomach and intestines removed.

Robin and Barry, however, were convinced they had a cheap and effective cure. Their research showed that most patients with ulcers were infected with a bacterium, which the two doctors called Helicobacter pylori.

The patients’ stomachs were producing more acid to get rid of the bacterium, but this failed because Helicobacter is resistant to acid attack. But it is vulnerable to the right antibiotics.

To prove the point, Barry deliberately infected himself with Helicobacter (he swallowed a flask of it) and soon developed gastritis — massive inflammation — which he cured with a short course of antibiotics. This was in 1984.

Nine years later, when I began filming with Robin and Barry, there was still widespread resistance to their claims, despite extensive proof they were right.

When I asked Barry how long he thought it would take to persuade his colleagues to take their claims seriously, he laconically replied, ‘Well it’s been ten years and ten per cent of doctors are treating ulcers this way. Perhaps in 100 years they will all be doing it.’

In fact, within ten years almost all doctors were doing it. Not least because Barry and Robin won the Nobel Prize for Medicine in 2004 for their work.

But back in 1994, when my documentary, Ulcer Wars, detailing their work, came out, the medical reaction was either indifference or hostility. A review in The British Medical Journal by a leading gastroenterologist described the film as ‘one sided and tendentious’.

However, patients with duodenal ulcers who’d watched the programme soon began demanding antibiotic treatment.

Many later wrote to me and as one man put it: ‘I saw your programme a week before I was due to have surgery, and it was only because my doctor was prepared to listen that I was cured by antibiotics rather than having a chunk of my guts removed.’

Why did it take so long for doctors to adopt this approach, despite overwhelming evidence that eradicating Helicobacter could change patients’ lives? This was a question that researchers from Harvard asked in 2019 — concluding that it was mainly because doctors get much of their information from pharmaceutical companies, and these companies had no incentive to promote a cheap alternative to their acid-reducing drugs (which, of course, you took for life).

The parallels with type 2 diabetes are clear. As the millions of those affected in the UK will know, type 2 is usually treated with medication. 

While this will reduce the long-term damage caused by high blood sugar levels, it doesn’t deal with the underlying disease — and like all medication, the drugs can have significant side-effects, particularly when you move on to injecting insulin.

So how long before there’s widespread acceptance that most cases of type 2 diabetes can be put into remission by a rapid weight-loss diet? 

It is beginning to happen, but I wouldn’t guarantee that NHS Choices will be telling you the good news any time soon.

Like us, worms need to sleep. And the way their bodies prepare for sleep is also surprisingly similar to humans — one of the key triggers for a bit of shut eye is the release of melatonin, also known as the ‘hormone of darkness’.

Melatonin is produced in your brain and levels rise when it gets dark (synthetic melatonin is a popular sleep aid and is used to treat jet lag — I find it very effective).Now researchers at the University of Connecticut have discovered how melatonin actually works — in worms at least.

It slows the release of neurotransmitters, substances that allow messages to travel between nerve cells. So melatonin effectively tells your brain cells to stop chatting to each other — the chemical equivalent of a giant ‘shhh’!

Covid-19 vaccines are like buses; you wait for one, then two come along, almost together, with other contenders coming close behind.

This week we learnt that the vaccine made by Moderna may be even more effective than Pfizer’s. That both are more than 90 per cent effective is fantastic news and a real poke in the eye for the sceptics who claimed we might never get a vaccine against Covid-19, let alone several.

These findings also suggest that our immune system is doing what evolution designed it to do: mount a strong response to the virus.

There was a fear that Covid-19 might mutate into a more resistant form — or that our immune response might weaken. 

Yet recent research suggests that while antibody levels tend to fall over time, your immune system retains a ‘memory’ of the virus. So if you encounter it again, your body is ready to begin churning out antibodies and T-killer cells.

Which makes me wonder why Boris, who’s had Covid, is self-isolating. He’s unlikely to be ‘bursting with antibodies’ as he claims, but he’s also very unlikely to get it again, or to be infectious, so I can’t see how he’s a threat to others. 

Our immune system has been severely tested by Covid, but as the new vaccines show, it just needs a bit of help to get back on top.

Covid-19 vaccines are like buses; you wait for one, then two come along, almost together, with other contenders coming close behind [File photo]

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