Microbiology Case Study: A 27 Year Old Man with Lumbar Pain

Clinical History

A 27 year old male with past medical history of mixed connective tissue disease was transferred from an outside hospital where he had initially presented for 6 days of progressively worsening lumbar pain preceded by 1 day of fevers up to 104 F, as well as chills and rigors. Also noted was pain and swelling in his left thumb and a mild rash present on the hands and feet. It is notable that the patient has multiple pets, including a rat.

Workup at the outside hospital included and MRI showing facet arthrosis and effusions at L4-L5 with mass effect on the S1 nerve root. Neurosurgery recommended biopsy of the lumbar spine by Interventional Radiology.

Laboratory Findings

Two sets of blood cultures at the outside hospital showed no growth at 5 days. Two sets of blood cultures obtained at our institution were positive at 15 and 29 hours, with a smear showing gram negative bacilli. The blood culture media was tested by nucleic acid hybridization and no targets were detected. When subcultured, there was only significant growth on the blood plate, with very small gray-green colonies that were not well appreciated

Image 1. Gram stain showing gram negative bacilli.
Image 2. Blood agar plate showing difficult to discern growth of very small grayish colonies.

A sample was sent to a reference lab for testing, which identified Streptobacillus moniliformis.

Discussion

In the United States, Streptobacillus moniliformis is the most common causative agent of rat bite fever, a relatively rare infectious systemic illness. This syndrome is also caused by infection with Spirillum minus, primarily seen in Asia, and rarely by Streptobacillus notomytis.1,2

S. moniliformis is a fastidious pleomorphic gram negative rod which grows slowly; in cases where there is clinical suspicion for rat bite fever, cultures can be held up to seven days. It is part of the normal nasal and oropharyngeal flora of rodents, with carriage rates of up to 100% in some rat populations. It can be found in oral, nasal, and conjunctival secretions, as well as urine, and can be transmitted to humans via bites, scratches, or oral contact. This includes kissing a pet rat or ingesting food or water that is contaminated with rat secretions.1,2

S. minus is a gram negative spirochete. It cannot be cultured on synthetic media, but may be visualized by Giemsa or Wright stain, or by using dark-field microscopy. Transmission of S. minus is similar to that of Steptobacillus spp., but has not been documented to be associated with contaminated food or water. (1, 2)

The clinical presentation of rat bite fever ranges from a mild case with only a flu-like illness to cases of severe sepsis. In untreated cases, the mortality rate is approximately 10 to 13 percent. Initial symptoms typically begin within 7 days of exposure for S. moniliformis and in 1 to 3 weeks for S. minus. These initial symptoms can include fever, myalgias, vomiting, pharyngitis, headache, and migratory arthralgias. If exposure was through a wound, it is typically resolved by the time symptoms develop, although it may reappear with ulceration, edema, and regional adenopathy in cases caused by S. minus. Cases associated with ingestion may have more severe vomiting and increased likelihood of developing pharyngitis.1,2

Symptoms may further develop to include a maculopapular rash on the extremities, and asymmetric polyarthralgias. The rash is seen most commonly on the extensor surfaces but can involve the palms and soles. Spontaneous remission may occur, but without treatment the fever can show a relapsing course, and the arthritis may last for several years. Possible complications include bacteremia, endocarditis, myocarditis, pneumonia, abscesses, septic arthritis, osteomyelitis, multiorgan failure, fulminant sepsis and death.1,2

Rat bite fever is usually diagnosed empirically based on consistent symptoms and history of rat exposure, because it is difficult or impossible to culture the causative organisms in the lab and there is no serologic test available. 16S rRNA sequencing can be used for definitive diagnosis, but only for certain sample types, and it is not always available.1,2

The empiric treatment of choice is penicillin, with the dose and duration being dependent on the clinical presentation. Ceftriaxone is also commonly used due to better ease of use in the outpatient setting, and tetracyclines are used in patients with beta-lactam allergies. For uncomplicated cases, most patients are treated for a total of 14 days; initially with IV antibiotics, and then transitioned to oral agents after 5 to 7 days if there is sufficient clinical improvement.1,2

Also remarkable in the patient’s history was a note indicating that they had been known to share drinks with his pets and instances of the pet rat licking the patient’s face. Initial treatment was vancomycin and cefepime, with vancomycin discontinued after the gram stain results. The patient was discharged before a definitive identification of the organism was made, with a plan for 6 weeks of outpatient treatment with ceftriaxone via infusion.

References

1.  King, Katherine Yudeh, MD, PhD “Rat Bite Fever.” UpToDate, Wolters Kluwer, 1 Jun. 2020. https://www.cdc.gov/rat-bite-fever/index.html

2.  “Rat-bite Fever (RBF).” Centers for Disease Control and Prevention, 1 Jun. 2020. https://www.uptodate.com/contents/rat-bite-fever?search=rat%20bite%20fever&source=search_result&selectedTitle=1~17&usage_type=default&display_rank=1

-Tom Koster, DO is a 1st year anatomic and clinical pathology resident at the University of Vermont Medical Center.

-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Associate Professor at the University of Vermont.

How One Phlebotomist Can Positively Influence Patient Care

Can you remember where you were when an experience showed you who you could be? I do. After graduating college, I wanted to find a way to harmonize my passion for community with my need to make an impact on society, so I began volunteering at the University of Colorado in the Cardiac Intensive Care Unit. I had an experience there that inspired me and has shaped my career’s trajectory.

During one quiet day on the unit a phlebotomy technician approached me with a task: to obtain a couple positive and uplifting movies for a patient who would most likely not make it through to the next day. Confident in my ability to achieve this, I hurried down to the volunteer office. As I looked through the selection of DVDs, I became disheartened. Nothing in their collection would do. All I could think was that this patient was living his last moments, and I couldn’t provide a happy distraction.  When I returned, my sorrow was quickly reversed when I found the technician by the patient’s bedside, using her phone to watch his favorite movie with him. I was so moved by her compassion,  I hosted a DVD drive to collect positive, uplifting movies for situations like this

I called numerous radio stations to get the word out and was featured on the local country radio station’s morning show to announce my drive and mission. My volunteer position, in combination with my customer service job, had allowed me to develop a large clientele and access to a community willing to help me in my efforts. I was touched by all the patrons who passed out flyers in the neighborhood about the drive. I ended up collecting over 200 DVDs, which I proudly delivered to the volunteer office. This intersection of medicine and community allowed me to experience firsthand the power of compassion in the medical community. I discovered my profound ability to bring together a community of unlikely individuals in an insightful and moving way. This experience also made me think seriously about the possibility of becoming a phlebotomy technician.  

Four  months, later I was practicing the art of phlebotomy in a hospital setting. As a phlebotomist I was doing more than drawing blood; I was learning the fundamentals of healthcare such as patient privacy, patient advocacy, and how to prevent the transmission of disease. I learned the importance of diagnostic and laboratory testing, how blood samples can provide clues to diagnosis and treatment.  Over the years my patients have shown me the meaning of tragedy and triumph, hope and disappointment, and most of all, the importance of being kind and gentle to those who are sick and in need. After drawing blood for more than 5 years with nearly 15,000 hours of patient care experience, I’ve learned the duty of a phlebotomist extends beyond the needle. It requires passion for diagnostic testing, patient education, patient advocacy, as well as dedication and commitment to others, to opportunities to learn, to engage in team collaboration and the ability to provide passionate medical care. Phlebotomy allows you to approach medicine with a multidisciplinary mindset and the ability to work in a medical community with a discourse of many facets under the unified goal of improving the quality of life across communities both nationally and abroad. 

Before I witnessed the compassionate care of a phlebotomy technician, I was unsure of how to combine  my passion for community with a rewarding career. In witnessing such compassion and care beyond duty, I was inspired to help, which ultimately inspired a community. That one experience showed me who I was supposed to be and what I am today – Kristi Nelson, Clinical Laboratory/Phlebotomy Coordinator.

That first experience now serves as the standard of care for my own phlebotomy team. I ensure we provide patient care that extends beyond the expectation, care that inspires change and creates a butterfly effect of positivity and compassion, in the same way that the phlebotomist had inspired me. This is just one example of how a phlebotomy interaction not only with a patient, but with other medical professionals (volunteers included) can influence patient care and the future of medicine in a positive way.

-Kristi Nelson is a Laboratory Coordinator for the Clinical Laboratory, Client Services and Customer Support at Orlando Regional Medical Center. It was through her work as a certified phlebotomist and emergency medical technician that Kristi found her passion for the healthcare community and leadership. Kristi’s leadership style follows the belief that if your actions inspire others to, learn more, do more and become more then you are a leader. Kristi demonstrates her passion for leadership by participating as the Compliance & Ethics Ambassador, Orlando Health Way Ambassador, and spokesperson for Orlando Health’s volunteer campaigns for the laboratory. Kristi holds a BA in Women’s and Ethnic Studies from the University of Colorado. Kristi is completing her BS in Neuro Psychology from the University of Central Florida and a dual Masters of Business Administration and Science Management and Leadership from Webster University.

A Wave of Testing Advances or Just a Drop in the Bucket?

Hello again everyone and welcome back! Thanks for joining last time in my discussion of social media as an inexhaustible force in professional development. This month…something different…

Yes, indeed, this month’s piece from me to you is a well-deserved break from your regularly scheduled pandemic reading. Consider this your COVID content caesura. Whatever will we discuss without the virus at the forefront of all of our media channels? What then could possibly hold our attention, satisfy our craving for knowledge and professional development, and quench our thirst for lab-driven news?

Liquid biopsies. Obviously. Get it? Thirst? Quench? Yea? I’m sorry, let’s just jump in…

Image 1. This is totally what happens during liquid biopsies, can you guys not visually see DNA? You might need better centrifuges/brighter bulbs—talk about your 10,000 ft. diagnosis, right? (Stock image: Cancer.org)

In my recent social media scroll-binging (which is absolutely normal nowadays, don’t judge) a small story about a published article in JAMA appeared nestled gently between powerful protest content, pandemic virology, and 2020 politics. The article, which was just a small summary of a study in Science that combined liquid biopsy testing with PET-CT imaging to screen and guide interventions for a variety of cancers detected among over 10,000 recruited patients. Detected cancers included anything from solid masses to lymphoma and were found from thyroids to the ovaries. Translation: earlier, more comprehensive detection of malignant neoplasms of all sorts ….*drum-roll, please* ….BY BLOOD TEST! If you’re not impressed with this outright, then don’t fret. This kind of lab testing technology is some Penn & Teller level medical lab science, and I’m very excited about it! I could do a whole talk on this, a professional one, a TEDx one even…scroll to timestamp 4:50:00—of course I’m gonna plug the TEDx talk here. You know me.

Image 2. Remember your A-B-P’s: Always be promoting. Like the TEDx talk I gave, where I talked a bit about liquid biopsies; I don’t know if told you that I did that … (Source: TEDx)

What’s a liquid biopsy anyway?

That’s a great question, I’m glad you asked. Basically, think of it as the pinnacle of precision medicine—the gate key for all diagnoses and prognoses for an individualized treatment regimen based on the principles of known mutagens and detectable proteins and particles. Put plainly, a simple blood test that tests your blood (or other body fluid) for specific biomarkers to clue us in on the presence of an insidious malignancy. What kind of markers? Circulating tumor cells, micro-amounts of relevant RNA, vesicles, modified platelets, and other parts of cells, specific proteins—the list is growing. New concept, right? Not exactly, we’ve known about circulating tumor cells for at least 70 years now (nope, not a typo) but we haven’t been able to accurately hunt for them. We’ve had a concept of this sort of testing since the 70’s but have had a hard time implementing its clinical utility.

Image 3. A clinical lab. Somewhere. Circa 1975. To be a fly on the wall when they decided to skip gas biopsies and jump straight from solid tissue to liquid—what a concept! (Source: Univ. Texas at Austin, College of Health Sciences, historical photo of flu drug development at Memorial Sloan Kettering, NY)

Until the present day. Much like PCR, NGS, MALI-ToF, specialized mass spectrometry, and other awesome tools in our clinical arsenal, the ability is surpassing the paradigm. Whoa—philosophy check: are we moving too fast? Is this a reckless exercise? Should we do more research? No, no, and yes (obviously, always). Liquid biopsies have had pre-Wright brother success in getting airborne, so I’m recruiting all you readers out there to get excited with me and garner interest. Previous limitations might have meant we needed histological diagnosis first—I see you, everyone on the AP side… but these papers I’m showing you all today say basically three things: (1) our technology for liquid biopsy is getting better, (2) we might not need any previous test/section and could use liquid biopsy as a screening tool, (3) combined with imaging studies, this could be highly predictive and clinically useful.

The published study said what…?

Okay, let me show you the papers in the order I saw them: the JAMA article was just a primer in their Biotech Innovations magazine, a summary of an interesting development in liquid biopsies. They referenced the recent study in Science and discussed how 26 of the 10,000 women aged 65-75 were confirmed from liquid biopsy (LB) to imaging with PET-CT and, ultimately, biopsy to conclude. It said that the “blood test combined with the PET-CT had a 99.6% specificity and a 15.6% sensitivity…” with more being detected by LB at follow up. If those numbers triggered you as much as they did me, then of course you would have done what I did and followed the breadcrumbs.

Image 4. (LEFT) the three-tiered method of testing in the Detect-A Science paper and (RIGHT) the nearly 99% specificity of the CancerSEEK liquid biopsy modality in the second referenced Science article.

Que the Science study. In it, the authors presented their three-step testing process, using “Detect-A” LB for baselines. Ultimately 26 cancers in 10 organs were detected by just the blood test; this was out of a total of 96 cancers detected overall in the 10,000 participants either through liquid biopsy, current standards, or other investigative work ups. They did the math and showed that despite a sensitivity of 15.7% for the combined LB and PET-CT, the positive predictive value rose from 5.9% to 40.6% when you combined those two modalities. But the other statistics weren’t as impressive. Back to the JAMA article! The very last line said, “a newer version of the test that has a 99% sensitivity without confirmatory steps is in development…” Okay, now we’re cooking with gas—or testing with liquids—whatever: that’s the holy grail of CP testing 99% sensitivity, 99% specificity! Do tell!

Much ado about liquid—this was less impressive. This last line referenced a Science paper used “CancerSEEK” LB in 1,000 patients with sensitivities from 70-98%, but fantastic 99% specificity. Different panel, different cancers this time. Interesting to note, was that, applied to the specific incidence in the US population for the particular cancers detected by CancerSEEK, the sensitivity was around 55%. And, they managed to keep the cost relatively low at under $500 per test. (Sorry, if a red light just went on while you read this, CMS is probably recording now…) Well, this left me wanting. I’ve read so little about LB’s in recent years, is no one working on them? Well no, I was just busy, there’s tons of stuff out there, silly.

In just the past year alone, the American Journal of Clinical Pathology published 10 pieces on liquid biopsy cases, education, and utility for all kinds of malignancies from cytology to hemepath! AJCP—that’s us guys, it’s happening right here, right now! I told you we’ve got to do a PR run on this stuff and get it out there.

Is this the future? Are we in it now?

I’m happy to report that yes! This is indeed the future, well at least as thought of by the folks that conceptualized liquid biopsies 70 years ago. No hover-cars, or hover-boards, or hover-anything really (not without a lot of tech and work) but we’re closer to small advances in medical diagnostics!

Image 5. Maybe a better conceptual map of what liquid biopsies do. (Source: Gene Quantification)

Nature writer Catherine Alix-Panabieres put it very well when she wrote an Outlook piece this past March. On the one hand, liquid biopsies are a growing clinically useful tool in the synergy of addressing cancer in individualized medicine. On the other hand, we’ve known about this concept and have clearly been working on advancements in this testing technology for decades—it’s about time to come out of the shadow and push into widespread utility, including them in cancer algorithms, and redefining the ways in which cancer work-ups are developed in clinical trials, regulated by safety, and integrated into the toolkit of oncologic diagnostics. In my recent interview with People of Pathology Podcast show-runner, Dennis Strenk, I said we’re not quite ready to replace tissue biopsies yet—but are we close?

When do we go from pushing glass to pushing tubes?

See you next time!

References

Abbasi, J (2020) Blood Test Flags Multiple Cancers in Large Study, JAMA. 2020;323(22):2239. doi:10.1001/jama.2020.9266 → read it here

Alix-Panabieres, C (2020) The future of Liquid Biopsy, Nature 25 Mar 2020 579, S9 doi: 10.1038/d41586-020-00844-5 → read it here

Bai, Y, and Haitao, Z (2018) Liquid biopsy in tumors: opportunities and challenges, Annals of Translational Medicine, 2018 Nov; 6 (Suppl 1): S89, doi: 10.21037/atm.2018.11.31 → read it here

CAP (2020) The ‘Liquid’ Biopsy, College of American Pathologists → read it here

Cohen, J, et al. (2018) Detection and localization of surgically resectable cancers with a multi-analyte blood test, Science 23 Feb 2018; Vol. 359, Issue 6378, pp. 926-930, doi: /science.aar3247 → read it here

Lennon, AM, et al. (2020) Feasibility of blood testing combined with PET-CT to screen for cancer and guide intervention, Science doi. 10.1126/science.abb9601 → read it here


-Constantine E. Kanakis MD, MSc, MLS (ASCP)CM is a new first year resident physician in the Pathology and Laboratory Medicine Department at Loyola University Medical Center in Chicago with interests in hematopathology, transfusion medicine, bioethics, public health, and graphic medicine. His posts focus on the broader issues important to the practice of clinical laboratory medicine and their applications to global/public health, outreach/education, and advancing medical science. He is actively involved in public health and education, advocating for visibility and advancement of pathology and lab medicine. Watch his TEDx talk entitled “Unrecognizable Medicine” and follow him on Twitter @CEKanakisMD.

COVID-19 Patients with “Green Crystals of …” STOP! Please Don’t Call Them That

Blue-green cytoplasmic inclusions in neutrophils and monocytes are a novelty in hematology. It is rare to see these inclusions on peripheral smears, and when we do, there is excitement, but sadness too, because, when noted, they usually indicate a poor prognosis and impending death. Thus, we have heard them called “green crystals of death” or “death crystals.” I know I would not want to read a family member’s medical chart and see reference to “death crystals.” It’s an insensitive term, and one the medical community is trying to discourage. And, in fact, though it typically does indicate a poor prognosis, not all cases lead to death. In published reports, it has been shown that short term mortality in patients with these crystals is about 60%.1

These rare inclusions are refractile and irregular in shape, and are found in neutrophils, and occasionally in monocytes. Color seems to be subjective here. They call them green when inclusions in photos or cells I am looking at look very blue to me. The color perceived may depend on the type of stain (Giemsa, Wright or Wright-Giemsa) used and how fancy we get in color names and descriptions. Or, maybe I’m just color blind! Some people (like my husband) are “lumpers” and call anything blue-green, blue, or green, but don’t recognize subtleties of colors. Thus, I guess to make everyone happy, or to compromise, the blue-green description may fit them best.

Image 1. Blue-green inclusions seen in neutrophils. Photos courtesy of Alana D. Swanson. UMMC

These blue-green inclusions were originally reported in patients with hepatic injury and failure. Laboratory results include elevations in AST, ALT and LDH. More recently, there have been cases with no evidence of hepatic injury. Researchers are now finding that these crystals can occur in patients with tissue injury other than liver, and in patients with multiorgan failure. In patients with no liver injury, what is a common factor is that LDH is elevated, indicating tissue injury. Additionally, along with these crystals, lactic acid levels can be used as a predictor of survival. Higher levels of lactic acidosis at the time crystals are noted is a negative predictor of survival.2

In trying to determine the clinical significance of these crystals, they have been subject to a number of different stains to determine their content. The association with hepatic failure led researchers to hypothesize that the crystals were a bile product in circulation. Since then, the crystals have been found to be negative in bile stains. When stained with other stains, Oil Red O showed positive in neutrophils, indicating high lipid content. The inclusions did not stain positive with iron stain or myeloperoxidase. Acid fast stains showed the inclusions to be acid fast positive.3 These crystals also show an interesting similarity to sea-blue histiocytes, which further associates them with tissue injury. After analysis, it is now thought that these crystals contain lipofuscin-like deposits representing lysosomal degradation products, and may be present in multiple types of tissue injury.2

With the current pandemic, I have seen reports of these crystals in COVID-19 patients. I have heard of fellow technologists seeing these, and a recent paper described the first reported cases in patients with COVID-19. These recent incidences may lead to new information about exactly what clinical significance they hold. About one third of COVID-19 patients have elevated ALT and AST, though it is not yet clear whether the liver dysfunction is directly caused by the virus, due to sepsis, or other complications of patient comorbidities. Many COVID-19 patients have mild disease, yet some develop severe pneumonia, respiratory complications, and multiorgan failure. Mortality is increased in these severely affected patients. To better understand and manage treatment for COVID-19, physicians seek to identify biological indicators associated with adverse outcomes.1

In a New York City study, Cantu and colleagues reported on six COVID-19 patients who presented with blue-green crystals in neutrophils and/or monocytes. All six patients had an initial lymphocytopenia, and significantly elevated AST, ALT, LDH and lactic acid at the time the crystals were noted. All of the patients had comorbidities, yet only two of the six presented with acute liver disease. Interestingly, in the six cases reported on in the study, only one had blue-green inclusions reported from the original manual differential. The others were found retrospectively when correlating the cases with patients known to have elevated ALT and AST. All patients died within 20 days of initial diagnosis.1

The consensus of several papers in the last few years is that these crystals are being underreported. As seen in the above study, the crystals were originally seen in just one of the six patients. A look back revealed the other cases. With an increase in COVID-19 cases in our facilities, these blue-green crystal inclusions may be a novelty that is wearing off. We may see a rise in their presence, and need to be able to recognize and report them. This information is important to report if clinicians are to use these crystal inclusions along with acute transaminase and lactic acid elevations to predict poor patient outcomes.

Clinicians, hematologists, and laboratory technologists should be educated and have a high level of awareness of these inclusions. The University of Rochester conducted a study a few years ago that noted that, because these crystals are rare, techs may not be on the lookout for them. Once techs see them, they seem to be on the alert and more are reported. The hospital instituted an “increased awareness” campaign, which resulted in an increase in detection. This revealed cases that were not related to liver injury, including patients with metastatic cancer and sepsis. However, an important correlating factor was that all of the patients had mild to severe elevations in liver enzymes. With more awareness, we are starting to see them in patients without hepatic injury, but with other inflammation and tissue injury.4

Image 2. Blue- green crystal inclusions seen in a patient diagnosed with sepsis and multiorgan failure. Photo courtesy of Karen Cable, YRMC.

Let’s raise our level of awareness of these maybe-not-so-rare crystal inclusions. And, please be sure to call them by their preferred name, blue-green neutrophil inclusions! Let’s not talk about death crystals or crystals of death.

Many thanks to my colleague Alana D. Swanson, MLS(ASCP)CM , University of Maryland Medical Center and Karen Cable, Hematology Section Lead, Yavapai Regional Medical Center, Arizona, for the photos used in this blog. 

References

  1. Cantu, M, Towne, W, Emmons, F et al. Clinical Significance of blue-green neutrophil and monocyte cytoplasmic inclusions in SARS-CoV-2 positive critically ill patients. Br J Haematol. May 26, 2020.
  2. Hodgkins, SR, Jones, J. A Case of Blue-Green neutrophil inclusions. ASCLS Today. 2019;32:431.
  3. Hodgson, T.O., Ruskova, A., Shugg, C.J., McCallum, V.J. and Morison, I.M. Green neutrophil and monocyte inclusions – time to acknowledge and report. Br J Haematol, 2015;170: 229-235.
  4. Patel,N, Hoffman,CM, Goldman,BJ et al. Green Inclusions in Neutrophils and Monocytes are an Indicator of Acute Liver Injury and High Mortality. Acta Haematol. 2017;138:85-90

-Becky Socha, MS, MLS(ASCP)CM BB CM graduated from Merrimack College in N. Andover, Massachusetts with a BS in Medical Technology and completed her MS in Clinical Laboratory Sciences at the University of Massachusetts, Lowell. She has worked as a Medical Technologist for over 30 years. She’s worked in all areas of the clinical laboratory, but has a special interest in Hematology and Blood Banking. When she’s not busy being a mad scientist, she can be found outside riding her bicycle.

Biomarker Testing for Cancer Patients: Barriers and Solutions Part 6

This month we will finish the discussion the common barriers to biomarker testing for cancer patients in the community. Lengthy complex reports is a relatively straightforward barrier to address, so I will pair it with the lack of education on guidelines barrier to complete this blog series on barriers to biomarker testing.

As you may recall, these are the top 10 barriers that I’ve seen to biomarker testing in the community:

  1. High cost of testing.
  2. Long turnaround time for results.
  3. Limited tissue quantity.
  4. Preanalytical issues with tissue.
  5. Low biomarker testing rates.
  6. Lack of standardization in biomarker testing.
  7. Siloed disciplines.
  8. Low reimbursement.
  9. Lengthy complex reports.
  10. Lack of education on guidelines.

Lengthy Complex Reports

Laboratory issued reports are typically developed by the lab and are often written in a manner that is easy to understand for other laboratorians. I’m guilty of writing long interpretive comments that are attached to every molecular diagnostics results. I would get irritated when the physician would call and ask questions that in my mind were clearly addressed in the interpretive comment. I thought the issue was they were not reading the comments (and this could be true). I now understand that the issue is that the comments were not written for the end-user.

When insourcing NGS I was fortunate enough to get feedback from the multidisciplinary team in the Molecular Steering Committee. One of the complaints that I heard loudly locally, that also resonated in the community, was the reports for NGS were way too long and they didn’t find value in half of the information that was in the report. When were shopping for the right cloud-based reporting software, I kept the feedback in mind from the oncologists. I was actually able to get proto-type reports from 3 different companies and provide them to the oncologists for them to score and provide feedback on the layout. This was invaluable in developing a report that worked well for the treating physician and not the laboratory.

Some of the feedback they gave that made a direct impact into the report we created was: bold the patient’s name so they can easily find it, use patterns as well as color-coding for drug resistance/sensitivity in case the document is faxed, and tell them everything they need to know to make treatment decisions on page one. These are things that were not intuitive to me. Having end-user feedback helped us generate a more useable report and enlightened me that the report needs to be written to an oncology audience.

Lack of education on guidelines

I’ve had the opportunity to do a great deal of educating around biomarker testing in the community. Physicians and nurses in the community want to provide guideline-driven care. Often when we are educating on changes to guidelines, it’s the first time the providers have heard of the change. NCCN for lung cancer alone had at least 7 updates in 2019. It’s amazing that the guidelines are able to keep up with the ever changing science and drug approvals; however it’s incredibly difficult to keep track of the changes.  

In large institutions we are fortunate enough to have specialized physicians that help keep the rest of us informed of changes in their area of expertise. Community physicians typically see and treat all types of cancers and don’t always have the network of specialists to keep them informed of changes for every cancer type. Many of them also do not have the time to attend conferences due to heavy workload.

 In order for the community physician to be informed of all of the changes to guidelines for every tumor type, we need to make sure the information is provided in a variety of methods. The information needs to be easily accessible. I have found that educational programs work well when brought to the community rather than trying to get the community to come to them. Pharmaceutical and diagnostic companies and even reference laboratories now have teams of individuals in roles that are intended to educate and not sell. They can provide in office education, facilitate webinars, lunch and learns, and dinner programs. If there is a champion for biomarker testing within the facility, you can develop your own educational program to be delivery locally at grand rounds. We discuss changes to guidelines within our Molecular Steering Committee. I’ve also talked to institutions where this education is given during tumor boards.

I don’t think there is a bad forum for education. Some physicians may prefer getting guideline updates from twitter; others will be more comfortable with a discussion with an expert, regardless of the medium it is important that we help facilitate education of guidelines in order to increase biomarker testing rates in the community.

-Tabetha Sundin, PhD, HCLD (ABB), MB (ASCP)CM,  has over 10 years of laboratory experience in clinical molecular diagnostics including oncology, genetics, and infectious diseases. She is the Scientific Director of Molecular Diagnostics and Serology at Sentara Healthcare. Dr. Sundin holds appointments as Adjunct Associate Professor at Old Dominion University and Assistant Professor at Eastern Virginia Medical School and is involved with numerous efforts to support the molecular diagnostics field. 

A Resident’s Perspective of SARS-CoV-2 Testing Using the Double Diamond Model of Design Process

During the 2019-2020 residency interview season, I “courted” – no better way to describe those interactions over lunch–several potential co-residents, who were eager to know why I came to University of Chicago (NorthShore) for my residency. My answers and those of my fellow residents would help the candidates determine how high they should rank our program, so I enthusiastically recalled things I liked when I interviewed at NorthShore about a year earlier. I had also recently completed my first microbiology rotation in residency and I had enjoyed seeing all of those factors work synergistically to improve patient health outcomes through improved testing. So passionately, I shared how I fell in love with the physical structure of the department which has almost all the labs and offices one floor, the automation of the labs-especially the core and microbiology labs, the capability and regular expansion of its molecular laboratory, the people and of course, “the feel” about NorthShore.

With these experiences, I looked forward to my second microbiology in March 2020, where I would learn more about the diagnostics of various microorganisms–E. coli: Gram negative short stubby/broad shouldered rods vs. Pseudomonas aeruginosa, Gram negative long slender rods, etc. (Un)fortunately, March came, but the novel coronavirus (SARS-CoV-2) had other plans for my learning. Cases of Coronavirus disease 19 (COVID-19), caused SARS-CoV-2[1] were increasing rapidly in the US, so laboratories, including ours had rapidly implement testing. Rather than have morning rounds and other educational activities where the differential diagnoses of several clinically relevant microorganisms were discussed, we had virtual and in-person meetings discussing what to do about one virus. These continued and by the middle of March, we had become the only non-government lab in Illinois and second in the Midwest that had developed a clinical PCR test for SARS-CoV-2. I was excited to be part of that success, but more so, about learning how we achieved that as a team.

Our approach could be summarized using the Double diamond or 4D model of design process which consists of four phases: Discover, Define, Develop and Deliver (Figure 1).

Figure 1. Double diamond or 4D model of design process which consists of four phases: Discover, Define, Develop and Deliver. Plan Do Study Act (PDSA) is an iterative model of quality improvement embedded in the 4D design process.
  1. In the discover phase, a phase of divergent thought [2] and exploration, we identified from events in China and other parts of the world as well as some other states in the US that the community we care for could potentially be affected by the COVID-19 outbreak.
  2. The next phase- define- is a convergent phase where the problem to be solved, as well as the resources available and resources needed to solve it are delineated [2]. As we transitioned from the discovery to define phases-and recalling the 2009 H1N1 influenza outbreak about 10 years ago- it became evident that an epidemic of a relatively fatal respiratory virus which we knew very little about was heading our way. As clinical laboratory professionals, our objective was to help identify members of the community who had been infected through testing so appropriate steps could be taken to sequester and care for them. Among our available resources was our molecular laboratory, but like most laboratories outside the Centers for Disease Control and Prevention, CDC we lacked the reagents, primers and authorization to run the test.
  3. Develop is the next phase in the process and this is a divergent phase where the team explores and refines potential solution to the issues and selects one[2]. This is often followed by the convergent deliver phase where one of the solutions from the develop phase is implemented. Feedbacks which are used for projects are also received during this phase[2]. But, the outbreak continued to evolve rapidly [3] with briskly increasing positivity rates[4] and some of the solutions we considered would require some time to be implemented and/or have long turnaround times. For instance, since we had a roust molecular laboratory, one option was to develop our assays and test in-house, while another was to send the samples to outside labs where they could be run. Running the tests in-house would have a shorter turnaround time and would be more efficient, which is extremely important considering the severity of COVID-19.
  4. Deliver is the last phase of the process.  We decided to develop a SARS-CoV-2 RT-PCR test at our institution, but we also knew we needed to put logistics and protocols in-place to deliver our solution.  For example, COVID-19 presents with flu-like symptoms but flu is common between December and March[5-7] so it would be impractical to expect to test all patients with flu-like symptoms – at least with the limited resources we had. In any case, it was clear that we would not have an ideal amount of time or information to develop and implement the perfect solution. As such, the revolving and fluid nature of the develop and deliver phases of our response is best depicted using the Plan Do Study Act (PDSA), an iterative model of quality improvement. As shown in Fig. 1, we developed and validated our assay, as well as developed an initial protocol for screening patients and logistics for patient-centered delivery in the “Do” step. Importantly, we also reviewed the effectiveness of these operations, and made necessary changes corresponding in the “Study” and “Act” steps respectively.

The prompt decision to implement in-house COVID-19 testing at NorthShore has proven to be the right one. To date we have tested 75,000 specimens and nearly 20,000 tests have been positive. Success which was possible because of the factors which made me come to NorthShore, amongst others. The LEAN, bright and capacious design of the department limits the innate barriers of hierarchical organizational structure; encouraging seamless horizontal and vertical intradepartmental consultation and collaboration as COVID-19 led us into uncharted territory. Also, having a molecular lab that regularly expands its capability made the decision to test in-house relatively easy. In addition, having an automated microbiology lab made it easier for staff to be flexible and deal with the various demands of testing for a new bug in a pandemic. And of course, the people at NorthShore who are ready to volunteer, take up new roles or change shifts to accommodate the demands of a rapidly evolving pandemic, stay in constant communications and provide feedback, and who make everything else at NorthShore work!

References

  1. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200130-sitrep-10-ncov.pdf?sfvrsn=d0b2e480_2
  2. Council, Design. “Eleven lessons: Managing design in eleven global companies-desk research report.” Design Council (2007).
  3. https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/summary.html
  4. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200324-sitrep-64-covid-19.pdf?sfvrsn=723b221e_2
  5. https://www.who.int/news-room/q-a-detail/q-a-coronaviruses#:~:text=symptoms
  6. https://www.cdc.gov/flu/symptoms/symptoms.htm
  7. https://www.cdc.gov/flu/about/season/flu-season.htm
  8. Christoff, Patricia. “Running PDSA cycles.” Current problems in pediatric and adolescent health care 48.8 (2018): 198-201.

Adesola Akinyemi, M.D., MPH, is a first year anatomic and clinical pathology resident at University of Chicago (NorthShore). He is interested in most areas of pathology including surgical pathology, cytopathology and neuropathology -and is enjoying it all. He is also passionate about health outcomes improvement through systems thinking and design, and other aspects of healthcare management. Twitter: @AkinyemiDesola

-Erin McElvania, PhD, D(ABMM), is the Director of Clinical Microbiology NorthShore University Health System in Evanston, Illinois. Follow Dr. McElvania on twitter @E-McElvania. 

Unwritten Safety Rules Every Lab Professional Should Know

Many years ago a woman purchased a cup of coffee in a restaurant drive-through. Not having a cup holder available in her car, she placed the cup between her legs to hold the coffee while she reached for money to pay for it. She burned her legs, sued the restaurant, and actually won her court case. Now such restaurants are required to warn customers with signs stating the obvious; “coffee served hot.” Before this regulation came to be, however, many people were aware of the possible danger of placing a hot cup near their skin. Does having a posted sign make customers safer? What about the lab environment? There isn’t an explicit safety regulation written for every action that could create an unsafe situation. So what are a few of the hidden and maybe no-so-obvious things might your staff need to know in order to keep safe?

You can’t chew gum in the laboratory. It’s true, but sadly, it’s not written down anywhere as a regulation. OSHA’s Bloodborne Pathogen standard says that “eating, drinking, smoking, applying cosmetics or lip balm, and handling contact lenses are prohibited (in the lab).” It says nothing abut gum, throat lozenges, hard candy, or even chewing tobacco. The unwritten rule is that OSHA is trying to prevent hand-to-face contact while working in an area where infections can be acquired easily this way. There are multiple routes of entry via mucous membranes- a major source of pathogen exposure- your mouth, nose, and eyes. Laboratorians should always keep their hands away from their face when working in the department. These activities are just another opportunity for hand- to-mouth contact. While you might be able to show the safety officer you are putting these things in your mouth outside of the lab, you would not be able to prove that to an inspector, and they will rightly cite you for it. If you need help enforcing this, be on the lookout- by the end of the year there will most likely be a regulatory body that addresses gum chewing directly.

How long should staff wear PPE? During the COVID-19 pandemic, many have asked about the effectiveness of various PPE and have looked for written guidance discussing how long it should be worn. In general, studies show that gloves lose barrier effectiveness in about two hours. Wear them that long if they are not visibly soiled while in use in the lab. Lab coats- disposable or reusable- can be worn for one week in the general lab setting unless something is spilled on them. Once a new coat is worn, the outside is considered contaminated, but that does not mean it cannot be re-used. It is wasteful to change coats every day unless there is a reason to do that (i.e. in a specialty lab where cross-contamination will be an issue). Face shields worn by staff can be reused as well, and they can be cleaned with alcohol-based products for disinfection. Rarely should a wearable face shield or goggles be used only once before disposal.

Mesh shoes are not allowed to be worn by lab personnel. Again, other than in CLSI guidelines, it will be difficult to find that written clearly in lab safety regulations. Laboratory footwear should “be comfortable and cover the entire foot, including the instep and the heel. Because canvas shoes will absorb chemicals or infectious fluids, they are not recommended. Leather or a synthetic, fluid-impermeable material is suggested. OSHA’s PPE standard does insist that employers take measures to protect the feet of employees. In the lab and specimen collection setting, that means footwear needs to protect from biohazard materials, chemicals, and even sharps. Mesh or canvas shoes do not fit the bill, and neither do clog-style shoes (even if they have a heel strap). If you need to, set your lab’s footwear policy through the dress code or maybe the Chemical Hygiene Plan. If staff tells you they can’t find this type of footwear, tell them to look harder. All across this country, hundreds of laboratory employees are wearing the appropriate shoes, and they are available at several different stores.

Often, because these safety rules are “unwritten,” staff will challenge you on them. It can be difficult to try to enforce these important safety measures if you can’t properly educate the staff about why they exist. Be sure to know your regulatory resources, and don’t be afraid to dig deeply into the references to find the answers you seek. Lab leaders can write their own policy, and it can go above and beyond what the regulations state if needed. The safety standard may not be clear and direct, but it these are still important measures to take. Just like that lady may have needed a sign to prevent her from putting hot coffee in her lap, your staff needs clear safety guidance to keep them safe from a lab-acquired injury or exposure. Provide the tools they need to remain happy and healthy members of your lab team.

Dan Scungio, MT(ASCP), SLS, CQA (ASQ) has over 25 years experience as a certified medical technologist. Today he is the Laboratory Safety Officer for Sentara Healthcare, a system of seven hospitals and over 20 laboratories and draw sites in the Tidewater area of Virginia. He is also known as Dan the Lab Safety Man, a lab safety consultant, educator, and trainer.

Pathology and Histology Services Being Developed at the Biamba Marie Mutombo Hospital (HBMM), Kinshasa, Democratic Republic of the Congo (DRC)

Dikembe Mutombo Foundation

The Dikembe Mutombo Foundation (DMF) was created by NBA Legend Dikembe Mutombo in in 1997 with a mission to improve the health, education, and quality of life for the people in his homeland, the Democratic Republic of the Congo (formerly Zaire).

It took 10 years of intense work and many challenges but in December 2007, the Biamba Marie Mutombo Hospital named in memory of Dikembe’s mother opened its doors to patients in the capital city of Kinshasa, DRC. Dikembe personally contributed more than $23 million to build and equip the hospital. The total cost of the new hospital was $29 million.

The hospital currently has close to 170 beds with an ultimate future capacity of 300 beds. It is a modern facility with state-of-the-art equipment including a new donated CT scanner (the first in the DRC.) This general hospital has the following traditional services: primary care, internal medicine, pediatrics, surgery, OB-GYN, surgical subspecialties such as neurosurgery, orthopedics, urology, and ENT. The goal for the hospital is to provide quality care and to train a cadre of health professionals who in turn will continue to build capacity in the health institutions of the country. Hospital management espouses the following values: respect for the dignity of the patients, professionalism, continuous quality improvement, transparency, and accountability. Currently, the hospital is the most modern, if not the best in the country and to date it has treated close to 500,000 patients.

In 2017, Dikembe Mutombo was honored by the Harvard University Medical School for his ongoing humanitarian efforts and dedication to health care during the Global Health Catalyst Cancer Summit in Boston. The three-day summit, hosted by Dana-Farber Cancer Institute, Brigham and Women’s Hospital (BWH) and Harvard Medical School, brought together African ambassadors, ministers of health, celebrity cancer advocates and global health stakeholders to discuss cancer and examine its global effects on society.

Background

In 2016, the Dikembe Mutombo Foundation successfully implemented a Women’s Oncology Institute at the Biamba Marie Mutombo Hospital (BMMH) in the capital city of Kinshasa. Using classic bedside and surgical teaching methodology, aided by low-cost telecommunications technology, and wise infrastructure investments, the Friends of Africa, Inc. (led by Dr. Groesbeck Parham) has been able to successfully build effective, Congolese-led programs for the early detection and treatment of female cancers at BMMH, thereby providing public access to these critical life-saving services for the first time ever in the DRC. Widespread access to such services is known to result in significant alterations in cancer death rates.

Several months ago, the hospital purchased a new ultrasound machine from GE Healthcare to aid in evaluating breast and abdomino-pelvic abnormalities for the female cancer patients.

Cervical Cancer Early Detection and Treatment Clinic

·     A new Cervical Cancer Early Detection and Treatment Clinic was opened at BMMH in July 2016, under the leadership of the Congolese healthcare providers that were trained in Zambia by Dr Groesbeck Parham.

·     During opening week 8,800 women requested cervical cancer screening services and 3,000 were accommodated

·     To date (July 2016-November 2017), the clinic has screened over 15,000 women for cervical cancer, the largest number ever reported in the DRC.

·     Almost 1,000 women (1 out of every 14 screened) were found to have cervical pre-cancer, all of whom were treated on the same day (the largest number ever reported in the DRC), using modern outpatient techniques.

Through intensive, quarterly, hands-on training demonstrations held at BMMH, a team of board-certified U.S. gynecologic oncologists from the University of North Carolina, Chapel Hill, successfully trained a local cadre of Congolese gynecologists to safely and effectively treat women diagnosed with invasive cervical cancer using oncologic surgical procedures. This novel form of competency-based surgical training was developed in Zambia and is specifically designed to rapidly build surgical proficiency in resource-constrained settings, based on the principles of “Deliberate Practice”, intense replication, and mental narration of a limited repertoire of surgical procedures. 

Using an approach tailored specifically for training surgeons in resource-constrained environments, a team of U.S., board-certified breast surgical oncologists from the University of Arkansas (led by Dr. Ronda Henry-Tillman) successfully trained local Congolese general surgeons to safely and effectively perform surgical procedures that are fundamental to the modern treatment of breast cancer. The training approach was identical to the one used to train gynecologists to perform cervical cancer surgery. To date 81 patients with breast cancer have been treated with surgery by the newly trained team of Congolese general surgeons, under the tutelage of U.S. breast surgical oncologists. All surgeries have taken place in the newly formed Breast Cancer Surgical Unit at BMMH.

In summary, the following has been accomplished:

  1. Developed a local Congolese workforce that has the capacity to provide modern, high quality cervical and breast cancer early detection, diagnostic and treatment services, and to train others
  2. Established two new female cancer (cervix and breast) specialty clinics at BMMH
  3. Established two new female cancer (cervix and breast) surgical units at BMMH
  4.  Leveraged web-based videoconferencing (Skype, Zoom) technology to facilitate continued education and develop an international women’s oncology community of practice, made up of Congolese, Zambians and Americans.
  5. Implemented a women’s oncology data collection system
  6. Designed culturally appropriate health promotion messages
  7. Initiated a cervical cancer prevention outreach program

 Women’s Oncology Care for Africa, known as WOCA. They are the visiting breast and cervical cancer team from the U.S.

Dr. Michael Hicks (L), gynecologic oncologist consultant from Detroit, Michigan, and Dr. Alex Mutombo Baleka (R) from Kinshasa, DRC, performing the first radical hysterectomy ever at BMMH in Kinshasa on a woman recently diagnosed with invasive cervical cancer during a cervical cancer screening program sponsored by the Dikembe Mutombo Foundation and supported by UNFPA.

Pathology and Histology

Histology is the next step that the HBMM hospital is working on establishing. This will provide a needed tool for a more complete diagnostic picture for better patient care. Presently, the hospital is working with 2 different Pathologists to help establish the diagnostic part of the Pathology lab. This is where I have come in to help the Pathologist develop their histology lab needs at BHMM. On my first trip over the hospital selected a team of medical techs to be the core of the histology lab. July 2019, I spent 3 weeks giving formal histology lab classes, organized our equipment and lab area, and started some initial hands-on training on basic histology procedures. On Feb 27th, 2020, I return to the DRC for my second trip to the HBMM hospital. The trip started on the 27th of Feb. in San Jose, Costa Rica. I spent parts of 2 days in Atlanta at the Mutombo Foundation picking up 2 donated microtomes and a double headed microscope to take over for the lab. My first task was to review my previous classroom teachings and spent more time on performing laboratory techniques. With the equipment we now have in the lab we were able to do some valuable training. We worked on tissue embedding, microtome sectioning, floatation bath pickup of the thin cut specimen tissues, and general good laboratory practices with the Pathology Lab. (photos)  Additionally, I was able to spend time visiting and training other histology groups in Kinshasa. I spend one day giving classes at the University of Kinshasa, in the Pathology Dept., to a hand full of Histologists from 4 different labs within the city of Kinshasa. My focus of visiting and presenting classes to those outside of the HBMM hospital was to educate the local labs more about basic histology, to help them to start networking to help each other, and for me to find out the available histological resources within the community. All this will not only help our present histology setup at the HBMM, but it will help the others develop better lab uniformity and quality to help each lab’s patients. We are still short a few things at the HBMM to get histology up and running. We would like to have the lab operational on our next trip to Kinshasa. We had projected the opening of Histology for July – Aug. 2020.  However, due to the COVID-19 pandemic and travel restrictions this timeline may not be met. We are still hoping for the histology\pathology lab opening at HBMM in 2020.

I would like to thank Dr. Dan Milner and Ms. Alpa Pandya from ASCP for their instrumental help in making this lab project possible. This is not the first time they have assisted me overseas and I hope it is not our last program to jointly help.  Additionally, I would like to thank Susan Johnson, Executive Director at DMF in Atlanta, GA, for her tireless support. She made sure everything came together for me. This included the obtaining (twice) a visa for me for the DRC.  This visa was not an easy task, especially for someone living in Costa Rica without a DRC Embassy in all Central America. Last, but of course not the least by any means, I would like to thank the Mutombos for their generosity and compassion for helping the medically underserved people of the Congo.

Each trip I have done overseas that I have provided teaching, basic or IHC lab setups, or fine-tuning of histology labs have all been different, but always rewarding. Just to note, many any of these trips I have done with the support of ASCP. I hope this article stimulates others to go out and help others. We all have something to offer. Please share your knowledge with others who many do not have the opportunities that you have been given. Do not let borders or languages be a deterrent. Remember, everything is possible if approached correctly.

The grounds at Biamba Marie Mutombo Hospital, Kinshasa, DRC.
A portion of one histology class.
Teaching in the lab at HBBM.

-David J. Davis BS, HT(ASCP)QIHC is a certified Histologist and has his qualification in immunohistochemistry with ASCP.  He has been a histologist for the past 38+ years. He has worked in various capacities in 26 countries around the world. Since 1992 he’s been teaching and assisting the international community in histology. He’s retired, but definitely not finished working.

The Social Medium is the Message

Hello again everyone and welcome back to Lablogatory!

If you read my post last time, I talked about preserving integrity and delivery of our professional duty as laboratorians in the face of both overwhelming pandemic demands as well as working to  advocate for our field as more people realize each day what goes into every single lab result around the world. A run on sentence and a heavy discussion—and it was just in time to celebrate Lab Week 2020!

This time let’s expand on the second topic a bit. Advocacy in our profession and spotlighting our critical roles as pathologists and medical laboratory scientists. As much as you or I might agree that this is proof positive, just from looking at the regular old news media this year, it’s not so easy. But something that’s been quietly creeping higher and higher on the Lab-Med radar this past year or so is now growing faster than it ever has before: Social Media.

The medium you disseminate information on also translates a message about the author/speaker. For me, I was not only staying the course about data-driven testing science regarding COVID, but I took every ad-lib and opportunity to praise the medical laboratory profession. I praised laboratorians for their hard work, and took a minute to say clearly and plainly, that they are indisputably healthcare heroes in this season of notability. In doing so, I found myself addressing a more pressing pandemic: The Path and MLS pipeline problem. We have a serious issue with finding new medical laboratory scientists and medical students to go into our field. The main cause and culprit? Our essential clinical invisibility. As we are much less patient facing than our other colleagues, it’s difficult to expose younger students considering various careers in healthcare to our specialty. Cue Twitter, Facebook, Instagram, LinkedIn, and even TikTok.

Image 1. Throwback to the 2019 ASCP Annual Meeting in Phoenix, AZ. Dr. Kamran Mirza (left), myself, and Dr. Adam Booth (right) are all part of the growing community of pathologists/trainees plugged into the social network to advocate, collaborate, and spotlight our profession. Follow them both on twitter at: @KMirza and @ALBoothMD, they are champions of using social media as an educational connection.

I’ve talked about this before. And, of course, I’m biased: I’m on the official ASCP Social Media Communications Committee and was highly active in previous iterations including the #SoMeTeam as well as ASCP Social Media Ambassadors programs. Anyone who reads my pieces here knows I’m not social media shy—heck, I weaponized my online presence for residency interview season, networking around the clock to get my name and my work out there for programs to notice. Spoilers: it worked really, really well.

(If you’re one of those senior medical students who is preparing to practice the age-old tradition of wiping the internet clean of your presence, consider a 180 turnaround from that plan—at least if you’re applying to pathology…)

So what worked so well for me? Well, first some background. You know I’m on two ASCP committees, CCPD and Social Media. I’ve already told you I’ve been working the social media angles for a while now, at ASCP meetings, sharing content, etc. And I had a super busy, and super rewarding, residency interview season. With rotations and interviews at some amazing places, I was able to both learn a lot about what it is I really want to do and meet folks to talk about it with. All that being said, sometimes things just fall into place. Specifically, a global pandemic happened. …too soon?

I’m not going to rehash the early days of the pandemic for you, or talk about how I became involved on the ground floor of a lot of outreach and education efforts: that was sooo last month, I did that already (read it all here). But what I will talk about is the butterfly effect that each media engagement set into place for me.

Image 2. When everyone’s talking, the loudest microphone gets the audience. When no one’s making sense, the best content wins. Many of the talks and interviews since the very first ones with my friend and colleague Dr. Ajufo set up a cascade of content to answer some serious concerns during these strange times.

In effect, the order of events for me these last few months looked like this:

  • Writing pieces for Lablogatory¸ some based in scientific analysis of testing, some to address public health concerns and education.
  • Making small viral online tid-bits aimed at educating lay people about overall health, avoiding exposure, and what testing means.
  • Social media connection to join the #PathCast lecture series, of which my video has garnered approximately 20,000 individual views and was seen in almost 50 countries.
  • Invitations from CDC-funded training agencies to explain testing considerations, virology details in translational science, and discuss how those most vulnerable to social determinants of health are most inequitably affected by pandemic conditions.
  • Informal features where I was invited to discuss those intersectional tenets of medicine, public health, and socioeconomics with lay persons in a virtual group setting.
  • An interview with Lifehacker magazine’s Vitals section, to answer reddit-style ask-me-anything questions regarding COVID testing online live with open to the public availability.
  • Inclusion in Lifehacker magazine’s online podcast, where I was featured alongside other experts to discuss the effect of the pandemic on many aspects of life from health to finances.
  • An interview with The Endless Files Podcast¸ where I was invited as a content expert to discuss the connections between laboratory data, public health, public policy, and discuss the political climate surrounding coronavirus concerns all over the sociopolitical spectrum.
  • An interview with People of Pathology Podcast which gave me the chance to talk about my individual career path and transition from education about testing to advocacy and representation for our amazing profession.
  • The nomination and selection by my medical school faculty and peers to deliver the student charge at my formal, virtual, medical graduation.
  • …more are on the way!

Why am I listing these things? Is it my misplaced Greek hubris? Maybe. But before I fly too close to the sun, I’m trying to prove a point. That what started out as creating content on social media for health and wellness during a pandemic essentially became a snowball by summer. I was addressing pressingly relevant information during the obvious opportunity to step up and educate. But something else was happening; something I didn’t realize until recently. And whatever it was, I wasn’t getting there alone.

**All of this was made possible by social media recommendations and connections from friends and colleagues!**

PathCast? I was recommended by a pathologist friend on ASCP’s CCPD committee with me. The CDC-funded training? A former grad student friend of mine when I studied at Rush. Lifehacker? Made possible in a public call for content by our favorite medical lab scientist and Lablogatory editor, Kelly Swails. The Endless Files? Reached out to an old political science professor and friend at Loyola. People of Pathology? Social media connections with friends and CLS colleagues in Canada—you want to make things happen? Don’t go at it alone!

Don’t know how to get started in all this social media frenzy? Don’t fret. Basically, here’s a four-step process: make accounts on one or all of your favorite platforms, follow everyone you want to learn more from, share other’s content or your own frequently, and (most importantly) promote others before yourself! There are countless webinars and talks on how to use social media to leverage advocacy and education, just look at some of the greatest pathology teachers on Twitter: @KMirza, @CArnold_GI, @MArnold_PedPath, @RodneyRhode, @HermelinMD, @KreuterMD, @JMGardnerMD, and many, many more. But there’s more than just twitter! Many super talented folks team up to produce lectures, webinars, and even podcasts (check out the brand-spankin’-new PathPod here!)

Just dive in!

Image 3. Virtual graduation, social media outreach. 2-for-1 sale. In my on-screen graduation quote during the conferment of degrees, part of it read “don’t let me be the last pathologist you were friends with…” and during my student address, I implored my classmates and anyone else watching to consider creative, new ways to solve clinical problems. Maybe with new tools, new skills, and a new understanding of interdisciplinary collaboration. I also reminded people that our digital presence can indicate our professional message, as champions of truth in science.

In conclusion, social media is the new (old) heavy hitter in the medical world. Younger med students are getting access to more specialty information than they ever have before, informing and guiding their career choices. Specialists of all kinds share and reshare excellent diamonds of content that galvanize medical discourse everywhere from Twitter to TikTok. What does this do? It closes the gap between professionals across disciplines, shines new spotlights on fields that traditionally got stamped with basement autopsy stereotypes, and creates digestible and understandable bridges for lay people to access our jargon-filled discourse. It only goes up from here.

Post-script: if you haven’t noticed the racially charged, horrible situations adding to the tumultuousness of 2020, there’s another lesson in this. Social media again proves a most-valuable and all-powerful tool to mobilize, demonstrate, collaborate, and unify thoughts, ideas, and causes. I doubt we will ever be free of tragic moments in history, but when we come together as one collective we can use our various platforms to honor heroes, shame wrong doers, celebrate positive change, and highlight systemic failings that might hold us back from true progress, justice, and peace. That includes the medical world, as all things cross at the intersections of human life and human rights.

Thank you for reading! Stay safe, stay well, and continue to practice safe, compassion-informed social distancing. The pandemic isn’t over, and neither is our work.

Until next time!


-Constantine E. Kanakis MD, MSc, MLS (ASCP)CM is a new first year resident physician in the Pathology and Laboratory Medicine Department at Loyola University Medical Center in Chicago with interests in hematopathology, transfusion medicine, bioethics, public health, and graphic medicine. His posts focus on the broader issues important to the practice of clinical laboratory medicine and their applications to global/public health, outreach/education, and advancing medical science. He is actively involved in public health and education, advocating for visibility and advancement of pathology and lab medicine. Watch his TEDx talk entitled “Unrecognizable Medicine” and follow him on Twitter @CEKanakisMD.

COVID-19 Testing Explained

By this point I believe we are all tired of reading and talking about COVID. However based on reading comments on social media, it’s quite clear that there are a lot of misconceptions about COVID testing. For starters COVID-19 is the disease caused by the SARS-CoV-2 virus. So all of the tests we are using to assist in the diagnosis of COVID-19 are really looking for signs that the person was infected with SARS-CoV-2. There are also 3 main categories of tests for SARS-CoV-2 based on the target of the assay: RNA, antigen, and antibody.

Diagnosis of COVID-19 should be based on clinical symptoms, risk of exposure, test results and timeline. The diagnostic tests based on detection of SARS-CoV-2 RNA are the most commonly used and reliable for diagnosis of COVID-19.1 All of these assays are based on amplifying the viral RNA to detect the presence of the RNA. Most assays use some form of PCR to amplify the virus, however because the virus is RNA-based it has to be converted to cDNA with reverse transcriptase PCR before amplification and detection. TMA or transcription-mediated amplification is another chemistry that can be used to amplify the RNA to a detectable level. Both PCR and TMA based assays are very sensitive at detecting the virus especially within the first week after symptoms develop.1,2 Due to the RNA-based nature of the SARS-CoV-2 genome, the mutation rate is anticipated to be high. Most of the RNA-based assays have adopted a strategy to target 2 different areas of the viral genome to prevent missing the presence of the virus due to a mutation in the primer binding site.

A SARS-CoV-2 antigen test received EUA in early May. The test is designed with immunofluorescence-based lateral flow. This type of test is designed to detect SARS-CoV-2 proteins present on the outside of the virus. In general, this class of test is cheaper and faster than RNA-based testing however it is less sensitive (80% clinical sensitivity).3 The clinical specificity of antigen assays is shown to be 100%,3 therefore a positive result is reliable. These tests can be used for screening; however patients with negative results may still need to proceed to testing by an RNA-based method. Antigen based tests is typically more sensitive during the same timeframe when PCR testing is more sensitive, ie earlier in the course of disease.

SARS-CoV-2 antibody tests are the last class of tests. Seroconversion appears to occur within 7-14 days of symptom onset2 or 15-20 days post exposure to the virus.4 There are many different tests to choose from to determine if the patient has previously been exposed to SARS-CoV-2. The assays range from lateral flow cassettes to high throughput chemiluminescent based assays. Some of the SARS-CoV-2 antibody assays detect IgG, IgM, IgA or some combination of the 3 including total antibody without differentiating between the three. The latest studies have shown that some patients develop IgM first, some with IgG, and others had both IgG and IgM develop at the same time.5 Therefore differentiating IgG from IgM is not providing a timeline for acute infection as we have seen in response to other viruses. Although sensitivity and specificity vary widely between manufacturers total antibody detection appears to be more sensitive than IgG or IgM detection alone.4 The FDA recently pulled numerous assays off of the market due to poor performance.

It is important to note that even with the most sensitive and specific antibody test, these tests cannot determine if a patient has protective immunity. Unfortunately we don’t know enough about immunity with regards to COVID yet. Early studies are promising, showing that some level of antibody will likely provide protection from future exposure. We don’t know if there is a threshold of antibody that needs to be present before a patient is immune, will the immunity only decrease the severity and not prevent reinfection, and how long the antibodies are maintained after exposure. These will be important questions to answer before the clinical utility of antibody testing can be realized. Right now the test is useful to determine is a patient was previously exposed to SARS-CoV-2 and is helpful to address epidemiological questions with regards to prevalence of COVID-19 in the community. The antibody test should not be used for diagnosis of current infection due to the delay to seroconvert after exposure.

References

  1. Sethuraman, N., Jeremiah, S. S., & Ryo, A. (2020). Interpreting Diagnostic Tests for SARS-CoV-2. JAMA. doi:10.1001/jama.2020.8259
  2. Wolfel, R., Corman, V. M., Guggemos, W., Seilmaier, M., Zange, S., Muller, M. A., . . . Wendtner, C. (2020). Virological assessment of hospitalized patients with COVID-2019. Nature, 581(7809), 465-469. doi:10.1038/s41586-020-2196-x
  3. Quidel Sofia®2 SARS Antigen FIA. https://www.quidel.com/sites/default/files/product/documents/EF1438900EN00_0.pdf 5/29/2020.
  4. Lou, B., Li, T. D., Zheng, S. F., Su, Y. Y., Li, Z. Y., Liu, W., . . . Chen, Y. (2020). Serology characteristics of SARS-CoV-2 infection since exposure and post symptom onset. Eur Respir J. doi:10.1183/13993003.00763-2020
  5. Long, Q. X., Liu, B. Z., Deng, H. J., Wu, G. C., Deng, K., Chen, Y. K., . . . Huang, A. L. (2020). Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. doi:10.1038/s41591-020-0897-1

-Tabetha Sundin, PhD, HCLD (ABB), MB (ASCP)CM,  has over 10 years of laboratory experience in clinical molecular diagnostics including oncology, genetics, and infectious diseases. She is the Scientific Director of Molecular Diagnostics and Serology at Sentara Healthcare. Dr. Sundin holds appointments as Adjunct Associate Professor at Old Dominion University and Assistant Professor at Eastern Virginia Medical School and is involved with numerous efforts to support the molecular diagnostics field.