SMJ: September 2021 Vol. 114, No. 09

September 13, 2021 // Randy Glick

The Southern Medical Journal(SMJ) is the official, peer-reviewed journal of the Southern Medical Association. It has a multidisciplinary and inter-professional focus that covers a broad range of topics relevant to physicians and other healthcare specialists, including medicine; surgery; women’s and children’s health; mental health; emergency and disaster medicine; public health and environmental medicine; bioethics and medical education; and quality health care, patient safety, and best practices.

Association between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Lung Cancer

Scott A. Helgeson, MD, Mark R. Waddle, MD, Rebecca C. Burnside, MD, Yalew T. Debella, MD, Augustine S. Lee, MD, Charles D. Burger, MD, Zhuo Li, MS, Patrick W. Johnson, , Neal M. Patel, MD

OPEN: An Approach to Faculty Development for Underrepresented Minorities in Medicine

Juan Robles, MD, Tanya Anim, MD, Maria Harsha Wusu, MD, MSEd, Krys E. Foster, MD, MPH, Yury Parra, MD, Octavia Amaechi, MD, Kari-Claudia Allen, MD, MPH, Jose E. Rodríguez, MD, Kendall M. Campbell, MD, Dmitry Tumin, PhD, Judy Washington, MD

Early Impacts of the COVID-19 Pandemic on Telehealth Patterns in Primary Care, Mental Health, and Specialty Care Facilities in Texas

Omolola E. Adepoju, PhD, MPH, Minji Chae, BS, MS, M. Femi Ayadi, PhD, Omar Matuk-Villazon, MD, Winston Liaw, MD, MPH

Physicians-in-Training: From Digital Devices to Digital Amnesia

Ali Seifi, MD, Michelle Rodriguez, JD, MD, Seyedmohammad Jafari, HBSc

OPEN: Immune Checkpoint Inhibitor-Related Pulmonary Toxicity: A Comprehensive Review, Part II

Hazim Bukamur, MD, Akram Alkrekshi, MD, PgDip, Heather Katz, DO, Mohamed Alsharedi, MD, Yousef R. Shweihat, MD, Nancy J. Munn, MD

Analysis of the Effects of COVID-19 Mask Mandates on Hospital Resource Consumption and Mortality at the County Level

Steven G. Schauer, DO, MS, Jason F. Naylor, PA-C, Michael D. April, MD, PhD, Brandon M. Carius, PA-C, Ian L. Hudson, DO, MPH

Could Clinician Sensitivity to Cultural and Historical Considerations Help Reduce COVID-19 Deaths among Blacks?

David Kountz, MD, Fatima Rodriguez, MD, MPH, Veronica Vital, PhD, RN, Setu Vora, MD, Ryan Gough, BS, Jessica Seyfried, MPH, MSW

Best Practices for Survey Use in Medical Education: How to Design, Refine, and Administer High-Quality Surveys

Tanya Nikiforova, MD, MS, Andrea Carter, MD, MS, Emmanuelle Yecies, MD, MS, Carla L. Spagnoletti, MD, MS

ACMQ’s Virtual Healthcare Equity Summit

September 8, 2021 // Randy Glick

Registration is Now Open for the ACMQ Healthcare Equity Summit!

Where: Virtual

When: October 1–2, 2021

Registration: https://acmq.org/page/Conference. SMA members receive 15% off their registration fees. Go to your member dashboard under the benefits tab to find your code!

The theme of this year’s meeting is ‘Healthcare Equity: A New Paradigm in Quality.’ The Centers for Disease Control and Prevention states that, “Health equity is achieved when every person has the opportunity to attain his or her full health potential.” ACMQ is committed to making that potential a reality in the medical quality community.

Achieving health equity is a collaborative effort, which is why I’m hoping you can join me for ACMQ’s first-ever Healthcare Equity Summit, where we will share insights, diverse perspectives, and actionable takeaways on subjects such as:

  • Understanding social determinants of health: What they are, what they mean, and how they have a major impact on health outcomes
  • Becoming better acquainted with the relationship between SDOH and adverse healthcare outcomes
  • Broadening understanding of your own personal unconscious biases in order to change behaviors and improve patient care
  • And more!

Please note that Physician, Nurse, and Pharmacist CEUs are available.

Safety Around the Clock: Keeping a Senior with Alzheimer’s Safe Inside and Outside

September 7, 2021 // Randy Glick

Senior caregivers face an overwhelming array of responsibilities, from managing medications to just listening when their loved one needs a sympathetic ear. Providing for an elderly person’s safety seems pretty straightforward, yet even the most basic considerations can be overlooked. Seniors who need 360-degree care require careful attention to detail to avoid dangerous, even lethal threats in their own homes. For a senior with Alzheimer’s disease, safety is a minute-to-minute concern.

The degenerative effect on the brain is severely disorienting. Alzheimer’s impacts one’s judgement, sense of place and time, physical coordination and behavioral patterns. Seniors who suffer from Alzheimer’s may become confused and do unexpected things that can lead to serious injury for no other reason than they’ve forgotten it’s dangerous.

Dementia may cause a senior to do any number of dangerous things, anything from touching a plugged-in appliance with wet hands to wandering outside and getting lost in their own neighborhood, which happens to three of every five Alzheimer’s patients in the U.S. each year. In many ways, protecting an Alzheimer’s patient from harming themselves is like child-proofing a home. Caregivers must be diligent to prevent a potentially disastrous accident.

Take Precautions in Every Room

Most accidents are easily preventable if you thoroughly examine the home environment. For example, making sure doors are locked, placing safety knobs on the stove, installing childproof plugs in electrical outlets, as well as childproof latches on kitchen and bathroom cabinet doors can prevent a number of serious mishaps. All medications should be carefully locked away out of reach and floor space kept uncluttered with easily overlooked items such as shoes or electrical cords, which can cause a bad fall. Remove tables and furniture that have sharp corners or edges, and be sure that the bedroom has plenty of lighting.

Alzheimer’s patients with dementia may easily mistake a dangerous liquid substance for water, so be careful to lock away cleaning products like paint thinner and other dangerous liquids, such as rubbing alcohol. Lighters and matches should be put out of reach, and any poisonous household plants thrown away, just to be on the safe side. It’s worth taking the time to check with the National Poison Control Center at www.poison.org, or 1-800-222-1222, if you have any doubt about objects that could pose a threat to the senior in your care.

Bathroom Safety

Bathrooms represent one of the greatest threats to seniors with Alzheimer’s. Falls are a major problem. Grab bars should be installed next to the toilet and alongside the bathtub. Non-stick mats can also help prevent falls. Serious cuts can result if razors and scissors aren’t safely locked away in a cabinet. If you have a shower with glass doors, apply decals so the senior in your care doesn’t get confused. A well-lit bathroom can help an elderly individual with dementia identify objects and avoid falls, so make sure that all burnt-out bulbs are replaced in a timely manner.

Safe Outside

There are plenty of safety threats outside as well. Most home exteriors have features that can spell trouble for a senior with Alzheimer’s. Hard wooden or cement stairs can become slippery and produce a broken leg or fractured pelvis. Consider having a ramp installed to give an Alzheimer’s patient a smooth surface to walk on when entering or exiting.

Seniors with dementia frequently wander outside, become disoriented and get lost, which can have tragic consequences, so keep all external doors locked and always accompany the individual in your care outside. In some cases, it may be necessary to have the locks on the home rekeyed, which will require the expert services of a locksmith. You can find a local locksmith as well as ratings and reviews through a site like Angi.com.

 Maintaining an environment that’s familiar, well-lit, and free of potentially harmful objects and substances is essential as a caregiver. Periodically, make a visual survey of your care-recipient’s surroundings to keep them clear of dangers they could easily miss or fail to identify correctly. As a caregiver, it’ll make your job easier and keep your loved one out of harm’s way.

Photo courtesy of Pixabay

About the Author:
Lydia Chan is the co-creator of Alzheimers.net, a website that aims to provide tips and resources to help caregivers. After her mom was diagnosed with Alzheimer's, she found herself struggling with finding balance between the responsibilities of caregiving and her own life. She is passionate about sharing her knowledge and experiences with caregivers and seniors.

Posted in: Mental HealthPatient Education

The Role of Histamine in Depression

September 7, 2021 // Randy Glick

Recent research is suggesting that reduced serotonin levels due to bodily inflammation may explain the ineffectiveness of antidepressants for some people.

Depression affects about one in ten of the adult population in the United States and is a main cause of disability globally. Many individuals do not respond to pharmaceutical antidepressant therapy, indicating a need for an improved understanding of the development of depression.

Some emerging data points to the immune system, particularly the inflammatory response, as a potential contributor to depression. Stress-induced inflammatory signals can be transmitted to the brain and affect the activity of neurotransmitters.

One neurotransmitter frequently linked to depression is serotonin. Briefly, high levels of serotonin release in the brain are linked to elevated mood, whereas low levels of serotonin are linked to the symptoms of depression.

Many individuals with depression are prescribed selective serotonin reuptake inhibitors (SSRIs), to prevent its reabsorption, meaning more serotonin is available to pass messages between neurons. However, a significant proportion of patients do not find SSRIs beneficial.

A team from Imperial College London, UK, have investigated the link between inflammation, serotonin and the effectiveness of SSRIs.

Dr Parastoo Hashemi and colleagues measured serotonin movement around the brain by placing microelectrodes into the hippocampus of live mice. Then they injected the mice with an inflammation-causing toxin called lipopolysaccharide.

Within minutes, this inflammation led to "robust decreases in extracellular serotonin in the mouse hippocampus," they report in the Journal of Neuroscience.

"There is emerging evidence that inflammation plays a significant role in the clinical variability of SSRIs, though how SSRIs and inflammation intersect with synaptic serotonin modulation remains unknown," they write. "We show that these decreased serotonin levels [because of inflammation] are supported by increased histamine activity."

The team also found that under these conditions, the SSRI drug escitalopram was limited in its ability to increase serotonin, because the drug holds back histamine reuptake, keeping levels of histamine high. Furthermore, when histamine was lowered, the drug escitalopram was able to increase circulating serotonin levels.

"We found that the histamine in the brain was triggered by the inflammatory response and directly inhibited the release of serotonin, by attaching to inhibitory receptors on the serotonin neurons. These inhibitory receptors are also present on human serotonin neurons. So, this effect might translate to people.

"This work reveals a profound effect of inflammation on brain chemistry, specifically the rapidity of inflammation-induced decreased extracellular serotonin, and points the spotlight at a potentially critical player in the pathology of depression, histamine," the researchers write.

"The serotonin/histamine homeostasis thus, may be a crucial new avenue in improving serotonin-based treatments for depression."

Commenting on the work, Dr Hashemi said, “Inflammation could play a huge role in depression, and there is already strong evidence that patients with both depression and severe inflammation are the ones most likely not to respond to antidepressants.

“Our work shines a spotlight on histamine as a potential key player in depression. This, and its interactions with the ‘feel-good molecule’ serotonin, may thus be a crucial new avenue in improving serotonin-based treatments for depression.”

It is important to note that the histamine-reducing drugs used in this study are different to normal antihistamines, which will not boost the efficacy of SSRIs. In addition, more human studies are needed to investigate how inflammation may trigger a chain reaction that increases histamine levels in ways that impair the effectiveness of SSRIs.

Dr Hashemi concluded, "Inflammation is a whole-body response and is therefore hugely complex. Depression is similarly complex, and the chemicals involved are affected in myriad ways by both genetic and environmental factors. Thus, we need to look at more complex models of depression behaviors in both mice and humans to get a fuller picture of both histamine and serotonin's roles in depression."

The role of the brain histamine system on the effectiveness of SSRIs has not yet received a great deal of attention, but in 2015 a team from the University of Florence, Italy, looked at the mechanics behind this mechanism.

Patrizio Blandina, MD, and colleagues explain that the neurobiological changes that prevent antidepressants from working remain poorly understood. They believe that failure to respond to SSRIs may be due to "abnormalities of neurotransmitter systems that excite serotonergic neurons, such as histamine".

Previous experimental studies have shown interactions between the histamine and serotonin systems that share control of functions impaired in depression, such as appetite, cognition, emotion, and sleep.

So the researchers carried out tests on the brains of mice and found that the SSRI drugs citalopram and paroxetine are ineffective in mice that are prevented from synthesizing histamine.

In the International Journal of Neuropsychopharmacology they write, "Here, we report that behavioral and neurochemical responses to SSRIs exclusively, and not to other antidepressants, are abolished in mice genetically or pharmacologically unable to synthesize histamine. Our results demonstrate that SSRIs selectively require the integrity of the brain histamine system to exert their preclinical responses."

They conclude, "The present findings demonstrate that histaminergic neurotransmission is indispensable for behavioral and neurochemical responses to acute administration of SSRIs."

Hence it is likely that individual differences in antidepressant response may be determined partly by genetic variations affecting histamine production, which may prove good predictors of more effective treatments.

Further information on the role of the histamine system in depression comes from studies into the compound oleoylethanolamide, or OEA. This compound regulates the release of different types of neurotransmitters, playing an important physiological and metabolic role. These roles include activating the hedonic dopamine pathway and increasing histamine in the brain.

A study was carried out in 2018 by the same team at the University of Florence, showing that histamine-deficient mice do not respond to the antidepressant-like effects of OEA.

The scientists explain, "It has been suggested that the bioactive lipid mediator OEA possesses anti-depressant-like effects. We recently demonstrated that several of OEA's behavioural actions require the integrity of the brain histaminergic system, and that an intact histaminergic neurotransmission is specifically required for selective serotonin re-uptake inhibitors to exert their anti-depressant-like effect."

The purpose of the 2018 study was to test if OEA requires normally-functioning histaminergic neurotransmission to exert its antidepressant-like effects. They assessed OEA's potential as an antidepressant drug in mice with artificially reduced histamine by testing serotonin release following administration of OEA.

This "revealed a dysregulation of serotonin release induced by OEA mice lacking histamine," they report in the journal Neuropharmacology.

"Our observations corroborate our hypothesis that brain histamine and signals transmitted by OEA interact, and may be the basis for the efficacy of OEA as an antidepressant-like compound."

This work was followed up in 2019 by a team of researchers at Tabriz University of Medical Sciences in Iran. They examined the links between OEA, histamine, and depression, with a focus on satiety and overeating.

Their findings suggest that OEA "can exert satiety-inducing effects by activating the hedonic dopamine pathway and increasing the brain histamine". Hence OEA, together with histamine, are likely to play a role in the management and prevention of obesity.

Furthermore, a group of Spanish researchers in 2019 also found that "the integrity of histamine receptors appears to be indispensable for OEA antidepressant effects to take place". They add, "It is possible that OEA affects cognitive processes associated with the hedonic value of behaviors" such as eating, using tobacco and alcohol.

Interestingly, the University of Florence team explored the mechanisms by which OEA and histamine work together in the brain's amygdala. They tested the role of the brain histaminergic system in the cognitive effect of OEA by depleting rats of brain histamine. They also examined the effect of OEA on histamine release in the animals' amygdalas.

This "showed that OEA increased histamine release from the amygdala", they report. "Our results suggest that activation of the histaminergic system in the amygdala has a 'permissive' role on the memory-enhancing effects of OEA."

The team suggest that targeting histamine receptors "may modify the expression of emotional memory and reduce dysfunctional aversive memories as found in phobias and posttraumatic stress disorder".

Overall, there is compelling evidence from observations in both animal and human experiments that the histamine system is essential for healthy neurotransmission and the effectiveness of antidepressant medications.

Future research will doubtless explore further the mechanisms behind these effects, with results that are likely to improve our understanding of depression and lead to new avenues for pharmacological treatments.

References and Resources

  1. Hersey, M. et al. Inflammation-Induced Histamine Impairs the Capacity of Escitalopram to Increase Hippocampal Extracellular Serotonin. Journal of Neuroscience, 28 July 2021 doi: 10.1523/JNEUROSCI.2618-20.2021 https://www.jneurosci.org/content/41/30/6564
  2. Miller, A. H. et al. The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nature Reviews Immunology, January 2016 doi: 10.1038/nri.2015.5 https://www.nature.com/articles/nri.2015.5
  3. Munari, L. et al. Brain Histamine Is Crucial for Selective Serotonin Reuptake Inhibitors‘ Behavioral and Neurochemical Effects. International Journal of Neuropsychopharmacology, September 2015 doi: 10.1093/ijnp/pyv045 https://academic.oup.com/ijnp/article/18/10/pyv045/623738
  4. Costa, A. et al. Histamine-deficient mice do not respond to the antidepressant-like effects of oleoylethanolamide. Neuropharmacology, June 2018 doi: 10.1016/j.neuropharm.2018.03.033 https://doi.org/10.1016/j.neuropharm.2018.03.033
  5. Tutunchi, H. et al. A systematic review of the effects of oleoylethanolamide, a high-affinity endogenous ligand of PPAR-α, on the management and prevention of obesity. Clinical and Experimental Pharmacology and Physiology, 23 December 2019 doi: 10.1111/1440-1681.13238 https://doi.org/10.1111/1440-1681.13238
  6. Orio, L. et al. Oleoylethanolamide, Neuroinflammation, and Alcohol Abuse. Frontiers in Molecular Neuroscience, 9 January 2019 doi: 10.3389/fnmol.2018.00490 https://www.frontiersin.org/articles/10.3389/fnmol.2018.00490/full
  7. Provensi, G. et al. Histaminergic Neurotransmission as a Gateway for the Cognitive Effect of Oleoylethanolamide in Contextual Fear Conditioning. International Journal of Neuropsychopharmacology, 1 May 2017 doi: 10.1093/ijnp/pyw110 https://academic.oup.com/ijnp/article/20/5/392/2926457

About the Author:

Jane Collingwood is a medical journalist with 17 years experience reporting on all areas of medical research for online and print publications. Jane has also worked on a range of medical studies funded by the UK National Health Service within the University of Bristol in the South West of England. Jane has an academic background in psychology and has authored books on stress management and respiratory infections. Currently she is combining journalism with a national coordinating role on the UK's largest surgical research trial.

Posted in: Mental HealthPatient Education

Breakfast with the President at the 2021 Annual Scientific Assembly

August 24, 2021 // Randy Glick

“Do We Still Need Organized Medicine and Medical Associations”
...a special address from the AMA’s 176th President, Dr. Gerald E. Harmon

We are pleased and honored to announce that the American Medical Association’s President, Dr. Gerald Harmon, will be addressing attendees during SMA’s Annual Scientific Assembly! Plan to join us on Friday morning, October 29, 7:30-8:00 am Eastern time as he discusses, “Do We Still Need Organized Medicine and Medical Associations.” This message, which will impact all members of the healthcare community, will address advocacy, education, and important public health issues, as well as why association membership is so important.

Dr. Harmon is a member of the SMA Family of Medicine, and has been actively involved since 2017. His leadership in SMA has included serving on the SMA Services Board of Directors, and as Chair of SMA’s Budget and Finance Committee. 

Learn More About the Assembly Register Today

New committee members for 2021-2022

August 19, 2021 // Randy Glick
The new committee members joining committees for 2021-2022 are:
 
Alliance Committee
Carissa Anthony, MS
Kaylee Carter, RN
 
Education Committee
Cary Cavendar, MD
Richard Leggett, MD
Loretta Loftus, MD
 
Physician-in-Training (PIT) Committee
Trent Percy
Sangeetha Isaac
Andrew Sephien
Magnus Chun
Junaid Alam
Mohammed Afraz Pasha
Buckley McCall
Zachary Olivos
Posted in: Hidden

An Overview of Post-viral Syndrome

August 16, 2021 // Randy Glick

Post-viral syndrome is a wide range of complex conditions involving physical, cognitive, emotional and neurological difficulties that vary in severity over time.

These conditions frequently lead to a sense of tiredness and weakness, pain, difficulty concentrating and headaches that linger after the viral infection has cleared. Symptoms may continue for weeks, months or longer.

While post-viral syndrome may appear similar to other health issues, it is important to exclude other conditions to have a clear understanding of the problem. Post-viral syndrome is triggered by a reaction to a virus which does not resolve in the normal way but continues in the form of sustained inflammation.

Various microbial and viral infections are possible trigger factors for post-viral syndrome, including Epstein-Barr virus, cytomegalovirus, human herpesvirus, enteroviruses, Lyme disease and more.

For patients, a sense of fatigue persists regardless of rest or additional sleep. Painkillers are often prescribed for aches and pains. Patients are advised to conserve energy, practice stress management techniques and eat a healthy diet. The jury is currently out regarding the benefits of exercise, with many individuals reporting a worsening of symptoms.

Many viral infections can trigger post-viral syndrome, with individuals who have weakened immune systems appearing to be at heightened risk. It remains unclear why the effects of a virus can linger in the body. Some theories suggest that the virus 'overloads' the immune system, preventing healthy immune system resolution for weeks, months or years. Continued inflammation, mediated by proinflammatory cytokines, could be at play.

The conditions myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) both cause symptoms similar to those of post-viral syndrome, and there is uncertainty over possible links to initiating viruses. Research exploring this area is underway at many centres around the world.

ME and CFS are sometimes considered interchangeable names for the same debilitating illness characterised by profound fatigue and impairment that lasts for at least six months. Usually the patient also experiences cognitive issues, muscle pain, gastrointestinal problems and a flu-like feeling.

The World Health Organization classifies ‘Postviral fatigue syndrome’ - incorporating both ME/CFS and chronic fatigue syndrome - as a disorder of the nervous system. There are no standardized biological markers or tests so diagnosis is based on exclusion of other underlying physiological causes. The efficacy of therapies to manage symptoms varies between patients.

In a 2021 article in the Journal of Clinical Medicine, researchers from Latvia explain that due to its unclear origins, treatment of post-viral ME/CFS is complicated, but one of the initial problems is the insufficient diagnostic process.

They report that, "ME/CFS creates a significant shadow burden on society, even considering only the direct medical costs of undiagnosed patients - the number of whom in Latvia is probably at least five times higher than the number of diagnosed patients. A similar situation can be observed in other countries."

"Preventive measures are becoming significantly more important," they write, adding, "an integrated diagnostic approach and appropriate treatment could reduce this burden in the future."

Dr Charles Shepherd, medical adviser to the UK's ME Association and former sufferer, agrees that the underlying cause of ME/CFS is "subject to much uncertainty and medical debate".

In a 2015 summary document, he writes, "This is one of the reasons why doctors have differing views on how the condition should be managed. At one end of the spectrum of medical opinion are those - myself included - who believe that ME/CFS is caused by a physical disease process that results in a number of symptoms affecting different parts of the body.

"This has now been shown to involve the brain and central nervous system, muscle, immune and endocrine systems. Mental health symptoms, where they occur, are a consequence and not a cause of ME/CFS."

He points out that research into causation of ME/CFS "has to carry a serious note of caution - because the research has been carried out on a very diverse group of patients who have differing clinical presentations and almost certainly have different disease pathways".

But despite all the problems relating to definition and patient selection for research, he believes there is considerable agreement over a three-stage process in ME/CFS, involving factors that predispose, precipitate and perpetuate the various symptoms.

The predisposing factor may be a genetic predisposition, which then precipitates ME/CFS when a trigger event takes place, such as an infection.

"Most people with this illness pre-date the onset of their symptoms to an infection - normally viral but sometimes bacterial - from which they ‘fail to recover’ and continue to have ‘flu-like symptoms’, along with the very characteristic muscle and brain symptoms that are associated with ME/CFS," explains Dr Shepherd.

In terms of perpetuating factors, the situation becomes far more uncertain. It may be that ME/CFS is perpetuated by a combination of changes to the way in which the brain, muscle, immune and endocrine systems respond to the triggering viral infection, or other immune system stressor.

Brain and central nervous system abnormalities in post-viral syndrome have been investigated using a variety of techniques. There appears to be consistent evidence of abnormalities in the autonomic nervous system which may help explain symptoms such as sudden low blood pressure on standing and an increase in the pulse on standing, as well as the cold hands and feet experienced by some people with ME/CFS, and irritable bowel and bladder problems.

Abnormalities in blood flow to parts of the brain may also explain the cognitive symptoms such as problems with short-term memory and concentration, as well as poor temperature control and pain.

But what mechanisms lie behind this extended immune response to infection? One commonality among the viruses linked to ME/CFS is the ability to bypass and evade immune cells, and thereby alter immune cell functions.

The establishment of a persistent infection is influenced by immunosuppression which may cause and maintain chronic inflammation. This chronic immune system activation is linked to changes in regulation of the immune-system chemicals cytokines, which can set the stage for post viral symptoms.

Cytokines are produced in response to any type of infection and result in a range of symptoms that include loss of appetite, wanting to sleep more than normal, and aches and pains in muscles and joints.

Hence a build up of inflammatory cytokines in the central nervous system may lead to post-viral syndrome, with one possible pathway being the movement of cytokines across the blood brain barrier. Support for this idea comes from research in which patients given interferon alpha (a type of cytokine) as a treatment for hepatitis C develop an ME/CFS-like illness as a side-effect.

Some evidence suggests that chronic pain may be caused by inflammatory signals that are spread by glial cells throughout the nervous system, activated by cytokines.

In addition, ME/CFS is associated with changes in the activity of mitochondria in cells, the energy-producing organelles. This appears to allow enhanced viral replication together with reduced mitochondrial DNA replication and increased oxidative damage.

Recently the autoimmune elements of post-viral syndrome have become a subject of intense research. Viruses contribute to autoimmune diseases in a variety of ways. An abnormal immune profile after acute infection may allow for continuous reactivation and incomplete clearance of pathogens, resulting in tissue damage and an overactive yet ineffective immune response leading to inflammation and autoimmune changes.

So both the viral activity itself and the immune response against the viral infection may contribute to produce symptoms of the condition, although immune cell activity has been found to vary across studies of ME/CFS and even within studies.

In 2018, Dr Bhupesh Prusty of the University of Wurzburg, Germany, and colleagues report, "At least in a subset of patients, the mitochondrial dysfunction and elements of autoimmunity that characterise ME/CFS may be linked to viral pathogenesis.

"Lack of extensive analysis of molecular mechanisms linking viral pathogens to ME/CFS restricts our understanding of this disease. Future studies need to focus on this aspect of ME/CFS research."

They state that currently available data on the role of chronic viral infection with ME/CFS is still controversial, but shows "potential viral involvement for at least a subgroup of ME/CFS patients".

They urge clinicians to "assess the presence and markers of viral activity at the initial stage of the disease to evaluate possible etiological factors", and call for "longitudinal and standardised studies determining ME/CFS course and therapy effectiveness with follow-up measurements".

This research will allow prognosis of the disease and help develop a specific definition for diagnosis and treatment plans.

All researchers in this field agree that the only way that firm conclusions about causation can be reached is through well-designed studies using carefully selected patients.

Nevertheless, as Dr Charles Shepherd of the ME Association points out, "Important clues are emerging and new types of drug treatment are being assessed on the basis of these abnormalities. So there is now real hope that effective forms of treatment will eventually emerge."

References and Resources

  1. Medical News Today: What to know about post-viral syndrome, https://www.medicalnewstoday.com/articles/326619
  2. Healthline: Understanding Post-Viral Fatigue, https://www.healthline.com/health/post-viral-fatigue
  3. Patient.info: What you need to know about post-viral fatigue, https://patient.info/news-and-features/what-you-need-to-know-about-post-viral-fatigue
  4. Hickie, I. et al. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ, 16 September 2006 doi: 10.1136/bmj.38933.585764.AE, https://www.bmj.com/content/333/7568/575.long
  5. Stormorken, E. et al. Factors impacting the illness trajectory of post-infectious fatigue syndrome: a qualitative study of adults’ experiences. BMC Public Health, 13 December 2017 doi: 10.1186/s12889-017-4968-2, https://bmcpublichealth.biomedcentral.com/articles/10.1186/s12889-017-4968-2
  6. Araja, D. et al. Shadow Burden of Undiagnosed Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) on Society: Retrospective and Prospective. Journal of Clinical Medicine, 6 July 2021 doi: 10.3390/jcm10143017, https://www.mdpi.com/2077-0383/10/14/3017/htm
  7. Dr Charles Shepherd, Medical Advisor to the ME Association. What do we know about the causes of ME/CFS?, https://meassociation.org.uk/wp-content/uploads/MEA-What-do-we-know-about-the-causes-of-MECFS-Shepherd-2015.pdf
  8. VanElzakker, M. B. et al. Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods. Frontiers in Neurology, 10 January 2019 doi: 10.3389/fneur.2018.01033, https://www.frontiersin.org/articles/10.3389/fneur.2018.01033/full
  9. Rasa, S. et al. Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Journal of Translational Medicine, 1 October 2018 doi 10.1186/s12967-018-1644-y, https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1644-y

About the Author:

Jane Collingwood is a medical journalist with 17 years experience reporting on all areas of medical research for online and print publications. Jane has also worked on a range of medical studies funded by the UK National Health Service within the University of Bristol in the South West of England. Jane has an academic background in psychology and has authored books on stress management and respiratory infections. Currently she is combining journalism with a national coordinating role on the UK's largest surgical research trial.

Posted in: Medicine & Medical SpecialtiesPatient Education

Things to do in Orlando during the 2021 Annual Scientific Assembly

August 5, 2021 // Randy Glick

2021 Annual Scientific Assembly registrants can receive discounted rate for entry into Walt Disney WorldⓇ. Please contact us at customerservice@sma.org or call us at 800-423-4992 for more information.

Sam's Club offers discounted rates to Disney World and other parks in Orlando:

Walt Disney WorldⓇ:  https://serviceshub.samsclub.com/pages.php?sub=wdw

Universal StudiosⓇ: https://serviceshub.samsclub.com/pages.php?sub=usf

Disney Springs:
Disney Springs is a themed retail, dining and entertainment center inspired by Florida's charming waterfront towns, historic architecture and natural beauty. The sprawling promenade features 4 distinct neighborhoods―The Landing, Marketplace, West Side and Town Center—built around bubbling springs. Learn more here!

Other things to do in Orlando:

Fun Spot Park
Boggy Creek Airboat Adventures
Giraffe Ranch
Hollywood Drive-In Golf at Universal CityWalk
Kennedy Space Center Visitor Complex
Madame Tussauds Orlando
Andretti Indoor Karting & Games

Things to do in Orlando (TripAdvisor)

Posted in: Hidden

SMJ: August 2021 Vol. 114, No. 08

August 4, 2021 // Randy Glick

The Southern Medical Journal(SMJ) is the official, peer-reviewed journal of the Southern Medical Association. It has a multidisciplinary and inter-professional focus that covers a broad range of topics relevant to physicians and other healthcare specialists, including medicine; surgery; women’s and children’s health; mental health; emergency and disaster medicine; public health and environmental medicine; bioethics and medical education; and quality health care, patient safety, and best practices.

Impact of Depressive Symptomology on Pain and Function during Recovery after Total Joint Arthroplasty

Lauren A. Beaupre, PT, PhD, Sung H. Kang, MSc, Gian S. Jhangri, MSc, Tyson Boettcher, MD, C. Allyson Jones, PT, PhD

Developing a Transitions of Care Elective for Medical Students during the COVID-19 Pandemic and Beyond

Sherine Salib, MD, Abi Amadin, MD, MPH, W. Michael Brode, MD, Clarissa Johnston, MD, Snehal Patel, MD, Michael Pignone, MD, MPH

COVID-19 Patient Acceptance to Monoclonal Antibody Infusion: A Single Medical Center Experience

Angie Ton, MD, Dawn Francis, MD, MHS, Leigh Speicher, MD, MPH

CME Article: Improving the Quality of Inpatient Discharge Instructions: An Evaluation and Implementation of Best Practices

Benjamin A. Rodwin, MD, Victor P. Bilan, MD, Craig G. Gunderson, MD, Naseema B. Merchant, MD