Microbiology Case Study: A 26 Year Old Female with Diarrhea

Case Description

A 26 year old female with a past medical history of Hemoglobin SC disease (Hb SC) and iron deficiency anemia presented to the emergency department with lower abdominal pain and diarrhea for three days. She began having multiple episodes of watery diarrhea, followed by bloody diarrhea after eating at a restaurant. During this time, she also had fever, chills, body aches, and headache. The patient had been on a course of ceftriaxone and metronidazole started three weeks prior for sore throat, ear infection, and bacterial vaginosis. She completed her metronidazole course prior to the current illness. Abdominal computed tomography revealed splenomegaly and a mildly dilated, fluid-filled appendix without evidence of infectious or inflammatory abnormalities. Hemoglobin on admission was 11.1 mg/dL (Reference Range: 11.2- 15.7 mg/dL) and MCV 62.9 fL (Reference Range: 79.4- 94.8 fL), which is similar to her baseline.

Laboratory Identification

The patient underwent work up for community-acquired diarrhea. Stool cultures grew non-typhoidal Salmonella (Image 1). Blood cultures performed at the time of admission flagged positive with gram negative rods which were also identified as Salmonella species by MALDI-TOF. The organism was susceptible to ampicillin, ceftriaxone, ciprofloxacin, and trimethoprim/sulfamethoxazole. The patient continued on intravenous ceftriaxone and responded to therapy. She was discharged home on oral ciprofloxacin.

Image 1. Salmonella Microbiologic Diagnosis using Xylose Lysine Deoxycholate agar and Triple Sugar Iron slant. A) Non-typhoidal strains of Salmonella are lactose non-fermenting, hydrogen sulfide producing (black colonies) enteric Gram-negative rods on Xylose Lysine Deoxycholate agar (XLD agar). B) Non-typhoidal strains of Salmonella are Alkaline (pink) over Acid (yellow) with the production of copious amounts of hydrogen sulfide on Triple Sugar Iron agar (TSI).

Discussion

Hemoglobin SC disease (Hb SC) is the second most common hemoglobinopathy after Sickle Cell Disease (SCD, Hb SS) globally.1 Hb SC disease occurs when a patient inherits both hemoglobin S and hemoglobin C alleles. Hemoglobin S and C variants are caused by point mutations in the hemoglobin beta- chain, and both variants lead to reduced affinity to the alpha-chain. While hemoglobin C is an abnormal form of hemoglobin that does not cause sickling on its own, when co-inherited with hemoglobin S, the beta chains polymerize, causing red cell sickling when oxygen tension is lowered in the blood.2 Patients develop anemia due to reduced red cell lifespan (27-29 days for Hb SC vs. 15-17 days for Hb SS) and subsequent destruction of red blood cells.3

Complications arise from vascular occlusion and destruction of red blood cells, leading to gallstones, pulmonary infarction, priapism, and/or cerebral infarction. Other complications include avascular necrosis of the femoral head, bone marrow necrosis, renal papillary necrosis, retinopathies, splenomegaly, and recurrent pregnancy loss. Although Hb SC patients often exhibit similar symptomology to sickle cell disease, symptoms are typically milder and present later in childhood.2,3 In comparison to patients with Hb SS, Hb SC patients have milder anemia, less frequent sickle cells, and less severe hemolysis. While Hb SC patients have fewer sickling episodes compared to Hb SS patients, Hb SC patients have more severe retinopathy and splenomegaly. It is also important to note that the enlargement of the spleen is often caused by red blood cell sequestration and the optimal function of the spleen is significantly reduced (functional hyposplenia), which can lead to increased risk of infection from encapsulated bacteria.

Diagnosis of Hb SC disease is typically made by performing hemoglobin electrophoresis (Image 2). Hemoglobin electrophoresis separates the differing varieties of hemoglobin by size and electrical charge. Capillary electrophoresis separates hemoglobin variants based on the “zone” of detection where each variant hemoglobin appears based on a reference pattern. Normal hemoglobin (A, F, A2) is easily discriminated from variant hemoglobins (S, C, E, D), and quantification allows for detection of beta-thalassemia (increased A2 fraction). While useful as a screening tool, the hemoglobin variants identified in the “zones” are not specific. For example, Hb C and Hb Constant Spring share a zone, and Hb A2 shares a zone with Hb O- Arab. Variants detected by capillary electrophoresis are confirmed by a second method, and in this case Hb SC was confirmed by acid agarose gel (Sebia Hydrogel). When subjected to acid gel electrophoresis, Hb C and Hb S migrate in separate bands, while Hb A, A2, D, and E comigrate in the “A” band, and the “F” band may contain F in addition to the glycated fraction of normal adult Hb A. Patients with Hb SC disease will have variants detected in the S and C zones in capillary electrophoresis and lack signal in the A zone.4

Image 2. Laboratory Diagnosis of Hb SC disease includes hemoglobin electrophoresis and peripheral blood smear review. A) Hemoglobin capillary electrophoresis (pH 9.4) separates F, S, C, A2, A (Sebia, Capillarys 2 Flex Piercing). B) Acid agarose gel (pH 6.0-6.2) separates hemoglobins F, A, S, and C (Sebia, Hydragel Acid QC lane).  C) Peripheral blood smear morphology showing characteristic Hb SC forms including target cells, boat shaped cells (single arrow), red cell with crystals (double arrow), and hemighost cells (triple arrow).

Examination of the peripheral blood smear from a patient with Hb SC disease (Image 2C) reveals frequent target cells, boat-shaped cells (taco shaped), and only rarely contains classic sickle cells. Hemoglobin C crystals can be seen, both free floating and inside red cells, a feature of CC and SC disease but not seen in SS disease. Hemi-ghost cells and cells with irregular membrane contractions are also more frequent in Hb SC disease. In contrast, sickle cells are rarely observed in peripheral smears from Hb SC patients.

Salmonellaeare flagellated gram negative bacilli that are members of the Enterobacterales. Salmonellosis is typically foodborne in nature and presents as a self-limiting acute gastroenteritis.5,6 However, these organisms can invade beyond the gastrointestinal tract resulting in bacteremia.6 This case presents Salmonella as a cause of bacteremia in a patient with Hb SC disease following a bout of gastroenteritis. Although there is a well-known association between SCD and invasive infections with Salmonella, the incidence of Salmonella infection in patients with Hb SC disease has not been well studied. Patients with SCD, particularly those in Africa, are at risk for developing invasive disease caused by non-typhoidal Salmonella, including osteomyelitis, meningitis, and bacteremia. It has been hypothesized that disruptions in the gut microbiome and increased permeability of enterocytes makes SCD patients more prone to invasive Salmonella infections.6 Furthermore, the compromised function of the spleen in both patients with SCD and Hb SC disease increases the risk of disseminated infection by encapsulated bacteria and Gram negative rods. The spleen plays an important housekeeping role removing old or damaged erythrocytes, but also has an important immunological function housing memory B cells, producing antibodies and macrophages that phagocytize circulating bacteria, particulates or other debris and then present the antigens to other immunological cells in the spleen.7 Although sepsis caused by Salmonella is an occasional progression of gastroenteritis, this patient’s Hb SC disease likely increased the likelihood of bacteremia because of her functional asplenia.

References

  1. Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010;115(22):4331–6.
  2. Tim R. Randolph,24 – Hemoglobinopathies (structural defects in hemoglobin),Editor(s): Elaine M. Keohane, Catherine N. Otto, Jeanine M. Walenga,Rodak’s Hematology (Sixth Edition), Elsevier, 2020, Pages 394-423, ISBN 9780323530453, https://doi.org/10.1016/B978-0-323-53045-3.00033-7.
  3. (https://www.sciencedirect.com/science/article/pii/B9780323530453000337)
  4. Nathan, D. G., Orkin, S. H., & Oski, F. A. (2015). Sickle Cell Disease. In Nathan and Oski’s hematology and oncology of infancy and childhood (8th ed., pp. 675-714). Philadelphia, PA: Elsevier. Retrieved from https://www.clinicalkey.com/#!/content/book/3-s2.0-B9781455754144000206y.com/#!/content/book/3-s2.0-B9781455754144000206. Accessed 2022
  5. Bain, BJ. (2020) Haemoglobinopathy Diagnosis, Third Edition. Hoboken: John Wiley and Sons, Ltd
  6. Kurtz, J. R., Goggins, J. A., & McLachlan, J. B. (2017). Salmonella infection: Interplay between the bacteria and host immune system. Immunology letters190, 42–50. https://doi.org/10.1016/j.imlet.2017.07.006
  7. Lim, S.H., Methé, B.A., Knoll, B.M. et al. Invasive non-typhoidal Salmonella in sickle cell disease in Africa: is increased gut permeability the missing link?. J Transl Med 16, 239 (2018). https://doi.org/10.1186/s12967-018-1622-4
  8. Leone G, Pizzigallo E. Bacterial Infections Following Splenectomy for Malignant and Nonmalignant Hematologic Diseases. Mediterr J Hematol

-John Stack is a first year AP/CP resident at UT Southwestern Medical Center.

-Marisa Juntilla is an Assistant Professor in the Department of Pathology at UT Southwestern Medical Center. Dr. Juntilla is a board certified Clinical Pathologist and is certified in the subspecialty of Hematopathology.

-Dominick Cavuoti is a Professor in the Department of Pathology at UT Southwestern Medical Center. Dr. Cavuoti is a board certified AP/CP who is a practicing Clinical Microbiologist, Infectious Disease pathologist and Cytopathologist.

-Andrew Clark, PhD, D(ABMM) is an Assistant Professor at UT Southwestern Medical Center in the Department of Pathology, and Associate Director of the Clements University Hospital microbiology laboratory. He completed a CPEP-accredited postdoctoral fellowship in Medical and Public Health Microbiology at National Institutes of Health, and is interested in antimicrobial susceptibility and anaerobe pathophysiology.

-Clare McCormick-Baw, MD, PhD is an Assistant Professor of Clinical Microbiology at UT Southwestern in Dallas, Texas. She has a passion for teaching about laboratory medicine in general and the best uses of the microbiology lab in particular.

BOGO: Biopsy One, Get One Free

I’ve mentioned before how important it is to know clinical history before attending a biopsy, and I cannot stress this point enough. As the first line of screening, the intermediary between clinician and pathologist, the role of the cytologist is to prepare, assess, and convey. In a cancer center, we have three main populations: the patients with the unknown primary, the patients with the suspected primary, and the patients with the suspected metastasis. In the event of a suspected metastasis, we’ll review previous relevant pathology material if we have it onsite. Unless the clinician is requesting additional prognostic markers, the review process helps us eliminate the unnecessary repetition of immunostains (IHC) by confirming that the current material is morphologically consistent with the prior material. Sometimes we still perform old-school cytology without a plethora of ancillary studies. HA!

Most of the endobronchial ultrasound (EBUS) procedures performed at our institution are for lung cancer staging or differentiation between a lung cancer metastasis and an extra-pulmonary metastasis. Not that we don’t see the occasional sarcoid- or anthracosis-related process from time to time, but our most common indication is cancer. For an 88-year-old male patient with multiple lung nodules and both mediastinal and hilar lymphadenopathy, confirmation of metastasis was the main objective of the EBUS procedure. The patient’s pertinent medical history includes former tobacco use, squamous cell carcinoma of the lung (diagnosed percutaneously in 2022), clear cell renal cell carcinoma (s/p partial nephrectomy in 2020), prostate cancer (radiated in 2007), melanoma (excised in 2001), and cutaneous squamous cell and basal cell carcinoma (also previously excised in 2002 and 2008). With an extensive cancer history, the lung nodules and thoracic nodes could be any of them, although metastatic squamous cell carcinoma of the lung was clinically favored. My awesome cytologist colleague, Kelly, attended the EBUS procedure. The Rapid Onsite Evaluation (ROSE) was a clear-cut “adequate for diagnostic material,” and the attending pathologist added “tumor cells present.” The following morning, Kelly stopped by my desk to ask my opinion of the 12R (right hilar) lymph node she was screening. She said, “look at my dots. Do these look like the same cells to you? Or are they different? Because I feel like they’re different.” Before putting the slide on my scope, I asked, “so… like a combined adenosquamous? Or a small cell component?” She replied, “not small cell. Something… I don’t know, but they look different. The patient was recently diagnosed with lung cancer and has a history of renal cell.” I fixated on the H&E cell block slides (Images 1-3) before perusing the Diff-Quik and Papanicolaou-stained slides (Images 4-5). “Uhm… Why are there two different types of tumor cells here?! The cytoplasm here is so… vacuolated, but it’s not quite like lung adeno, and the other group… even the n/c (nuclear-to-cytoplasmic) ratio is different. What is this?” Kelly replied, “okay, so there are definitely two different types of tumor here.” I looked up, “It has to be. Absolutely, yes.”

Images 1-4. Lymph node, 12R, EBUS-guided FNA. 1-3: H&E cell block sections 1, 100x; 2, 400x; 3, 100x. 4: Diff-Quik stained smear.
Image 5. Lymph Node, 12R, EBUS-guided FNA. Pap-stained smear.

Kelly entered her diagnosis into our laboratory information system and brought the case over to the pathologist on cytology service for the day. She explained her thought process, and the pathologist also questioned if it was a combined process, such as a lung adenosquamous and maybe the original lung biopsy only sampled the squamous component. With the most recent clinical history of both lung squamous cell carcinoma and clear cell renal cell carcinoma, an IHC panel was appropriately selected. Later that afternoon, the pathologist exclaimed, “IT’S BOTH! IT’S SQUAMOUS AND RCC!” The clusters of squamous cell carcinoma did not stain for PAX8 (a renal cell carcinoma marker) (Image 6), and the same cluster stained positive for p40 (a squamous cell carcinoma marker) (Image 7). Within the same level of the cell block, the cluster of cells that appeared morphologically different than squamous cluster stained positive for PAX8 (Image 8) and negative for p40 (Image 9), confirming a renal cell carcinoma component. A small focus of p40-positive cells was present next to the p40-negative renal cell carcinoma (Image 9), further demonstrating mixed histology. This finding was shared with other pathologists, and the results were immediately called to the pulmonologist as this was a critical finding. Sometimes we encounter a partially involved node where the tumor cells are intermixed with lymphocytes, sometimes the lymph node yields more tumor than the primary site, and sometimes, albeit rarely, we encounter a lymph node infiltrated by two different carcinomas.

Images 6-9. Lymph Node, 12R, EBUS-guided FNA. Cell block section immunocytochemistry. Squamous cell carcinoma cluster – 6: PAX8-negative; 7: p40-positive. Renal cell carcinoma cluster – 8: PAX8-positive, 9: p40-negative (with small focus of p40-positive squamous cell carcinoma).

Due to the patient’s bulky disease and PD-L1 expression of 30%, the medical oncologists primary aim was to treat the squamous cell carcinoma first and follow up renal cell carcinoma therapy second. After the first few cycles of treatment, the lung nodules have decreased in size, but the thoracic nodes remain unchanged. Once the squamous cell carcinoma is controlled or demonstrates a more significant response, immunotherapy may be added to target both, with a tyrosine kinase inhibitor directed at renal cell carcinoma metastases in the event of progression.

-Taryn Waraksa-Deutsch, MS, SCT(ASCP)CM, CT(IAC), has worked as a cytotechnologist at Fox Chase Cancer Center, in Philadelphia, Pennsylvania, since earning her master’s degree from Thomas Jefferson University in 2014. She is an ASCP board-certified Specialist in Cytotechnology with an additional certification by the International Academy of Cytology (IAC). She is also a 2020 ASCP 40 Under Forty Honoree.

“Being a Doctor” Vs. “Doing Your Job”

I awoke to a text recently that simply said, “Can I ask you a question?” Having finished medical school 22 years ago, I get this very frequently and know from personal anecdotal statistics that it’s either a medical issue (high probability) or someone needs money (much less common). This is not a text from work nor is it from a channel that will result in additional funds deposited on my behalf. This is from an acquaintance, by which I mean it could be any of the following: family member, friend, colleague, ex-girlfriend of an ex-boyfriend, co-worker, random person I met somewhere, etc. I spent some time on the phone in response to this text, recommended a course of action, and solved the problem. The details of this discussion (or the hundreds of others I had over the years) are privileged and irrelevant. The point is that I was “being a doctor’. A problem was presented by a person in need with real concerns about their health (or a loved one’s), I assessed the information they provided, and suggested a next step. My advice is usually spot on and appreciated which stems from my being cautious but concerned. Another important feature of my advice derives from one of my mantras: “Don’t scare the straights!” (which I learned from the comic genius, Bill Murray, in Ghostbusters).

This is one of the hardest aspects of being a doctor (especially when you are a student). It’s really great that you recognize (sometimes immediately) that someone has a life-threatening illness… but they don’t need to know that unless they are within a safe, secure medical environment where action can be taken. Moreover, medical issues are private for the same reason. It’s pretty clear to all of us that we shouldn’t yell “Fire!” in a crowded theatre or even jokingly say words that sound like “bomb,” at an airport. But here’s a true story of what I mean with medicine. Many years ago, I happen to be on an airplane (at cruising altitude) coming back from Africa, where my friend, Paul Farmer (RIP), was also a passenger. Another colleague of ours (a surgeon) was also on the plane. Paul was having an eye issue which looked mild but irritating. Our colleague said, loudly in her confident tone, “Do you think it could he Ebola?” Paul and I exchanged a quick glance, both thinking, “Don’t scare the straights!” I think you see my point. But, for clarity, a personal example. One winter, my husband and I were returning from the city to our suburb, which required a brisk, long walk from the train. The sidewalks were icy and, in places, uneven. He stepped off and fell full force on his shoulder. The next morning he couldn’t move it and it was painful. My immediate thought was, “He broke his shoulder.” Did I say, “Dude, you totally broke your shoulder!” No. We were having an open house to sell our place and he was all stressed about it. So, I said, “Be careful with your arm and we will go to urgent care afterward.” This made him calm. I even made him drive to urgent care (it was not his dominant shoulder) to reassure him he was okay. In urgent care, the ortho surgeon (who happened to be that day’s coverage) walked in after the x-ray and said, “Dude, you broke your shoulder!” And my husband promptly passed completely out onto the examination table. It’s all about understanding the acuity of the situation and striving to not make it worse.

Have I ever been wrong? Of course! Because the only way to truly care for a medical concern is to evaluate it yourself in person with appropriate tools. And almost all of the times I have been wrong (which is only a few), there was some crucial aspect that was not shared because either it wasn’t known or there was discomfort with sharing.

But what I am describing is not unique to me. I’m quite sure every doctor gets these calls with frequency. It’s the purest form of practice because there is no financial transaction presumed, assumed, or demanded.

But what about “doing my job?” Let’s break that down. I work for a non-profit and have a private consultation practice (non-overlapping, non-conflicting). Currently, I am financially compensated (at about $175/hour (pre-tax)) for any/all of the following: health system implementation, grant writing/administration, education, research management, social media production/communication, expert scientific/business consultations, committee participation, abnormal laboratory case review, daily laboratory management, intra-operative consultation, market insights/research, etc. Not much of that sounds like I’m fighting death and stamping out disease at the individual patient level, the life task I as trained for in medical school. Importantly, I’m also hard salaried across all my work so I don’t do individual billing except for a few things like abnormal slide review. Many of my physician colleagues do have to engage in individual billing. But I think much of what I do still sounds very familiar to many of my physician colleagues who see patients every day. When (in my opinion) my physician colleagues should be spending every hour of every day “being a doctor,” as I described above, I fear they spend a lot of time instead documenting, managing, and administrating to ensure they are compensated. I am of the very unpopular opinion that healthcare should be free but I also believe healthcare workers should be compensated aligned to their impact on patients. The medical profit insistence paradigm continues to widen inequity while decreasing the care time for patients in lieu of format/template/documentation to justify billing. I have to spend time doing this non-patient care but, fortunately, they are limited because of the narrow slice of medical billing to which my services are privy.

Here is a specific example to demonstrate the difference I’m discussing. I received an abnormal smear to review from the laboratory. The white blood cell count was over 400,000 cells (ref 10 – 30), the smear was a “medical student”-level diagnosis, the patient was on a supposedly effective treatment, but they had left against medical advice. There are many ways to respond to this case. My question was, “Is this patient okay, right now?” and my immediate action reflex said, “This patient needs to see an oncologist right now.” But she left AMA. How you as a patient or doctor respond to this says a lot about you as a person but also about the fiscal constraints in which you work. What did I do? I called the patient who had, thankfully, been admitted elsewhere, and asked them to please have their doctor call me back. The doctor did, I told them the information, and my suggestion that oncology see them immediately. Oncology saw them a few hours later. Let’s summarize. I spent about 20 minutes reviewing all of the clinical and laboratory information, about 1 hour on the phone over 2 days, and about 10 minutes documenting all of this in the patient’s medical record. I was subsequently paid an additional $25 two months later for that documentation by the patient’s insurance company. So, I “did my job” for $16.67/hour over my base but I was also “being a doctor,” which likely was best for the patient. Which is most important at the end of the day? I certainly didn’t need the extra $25 but the patient definitely needed my input. Importantly, note that the insurance company valued my time at a 10-fold lower rate than did my hospital.

A recent study demonstrated that when nurse practitioners are used instead of physicians, healthcare costs were higher.1 This study follows other studies which have shown the opposite. I don’t have an opinion about quality of care, appropriateness, or territorial pissings in the current debate between MDs and NPs about scope of practice; in fact, I see NP’s quite frequently for my healthcare. But we are all being asked to always be conscious of costs in healthcare when all we should be focusing on is, “How is the patient doing right now?” Grand efforts, like task shifting domestically and internationally, are assumed to save money but they simply don’t do so universally. Where costs could be easily cut (i.e., administration) or outsourced (i.e., finance, HR, IT), they aren’t because C-suites are in charge of cost cutting. But doctors (and NPs and all front line medical workers) are the ones being told to be cost conscious and find cost savings—when their job should only be asking the question, “How is the patient doing right now?”

I love “being a doctor,” especially when I can help someone reach a positive outcome. I love “doing my job” because it’s variable, ever-changing, challenging, rewarding, and I feel my compensation is appropriate. I really love when “doing my job” and “being a doctor” align around the same task. Finding this alignment as frequently as possible produces the happiest healthcare workers and the best care for patients, in my opinion.

Note: As an employee of a 501(c)(3), my salary information is public knowledge.

Reference

  1. https://www.ama-assn.org/practice-management/scope-practice/amid-doctor-shortage-nps-and-pas-seemed-fix-data-s-nope
milner-small


-Dan Milner, MD, MSc, spent 10 years at Harvard where he taught pathology, microbiology, and infectious disease. He began working in Africa in 1997 as a medical student and has built an international reputation as an expert in cerebral malaria. In his current role as Chief Medical officer of ASCP, he leads all PEPFAR activities as well as the Partners for Cancer Diagnosis and Treatment in Africa Initiative.

Omicron: Variant of High Significance?

Omicron is now the dominant variant in the United States and gained that title faster than any variant before it. I have been tracking variants in the North Texas region since February of this year and detected the first Alpha variant (B.1.1.7). During this time, there were multiple substrains circulating. Some like Epsilon (origin California) rose in prominence then declined to extinction. Rise in Alpha (origin U.K.) and Delta variants (B.1.617.2, origin India) were tracked over the course of weeks, but Omicron has been tracked on a daily basis, since it is rising so quickly.

Many places are using S-Gene Target Failure (SGTF) as a surrogate for Omicron variant (Yale, University of Washington below).

Photo credit @NathanGrubaugh (Yale, Left) and @pavitrarc (UW virology, right)

SGTF occurs when the TaqPath COVID-19 multiplex test has 2/3 targets successfully amplify when the S-gene target does not or “drops out.”  This phenomenon was first observed in the Alpha variant, because the probe for this target overlapped a characteristic mutation: S:Del69_70 (deletion of the 69th and 70th amino acids in the spike protein from a 6 base pair deletion). This mutation is absent in Delta, but present in Omicron, so has been used as an early tracker of Omicron prevalence.

Most of this discussion is speculative and we won’t ever really know, but given the rate of transmission of this variant, it seems unlikely that it would have acquired so many mutations and not been detected before now. The most recent common ancestor is from over a year ago suggesting it was incubating for a long time.

We’ve seen a case of a person severely immunocompromised with no antibody response to vaccination + booster who still has an unmutated wild type strain in their system. With no immune pressure, the virus has not evolved.

However, in HIV+ patients with variable/ low immunity, there could be enough pressure to drive the immune evasion properties seen in Omicron. Southern Africa has over 30% of their HIV+ patients not on therapy who would be likely candidates for this type of host.

Did we see this coming?

Yes. Other immune evasive variants have arisen in areas with high prevalence of previous infection (Brazil/ S. Africa). Organisms evolve just enough to overcome the challenges in their environment. Thus the level of immunity provided by various immune exposures are approximately:

 Previous infection < 2x Vaccine < 2x Vaccine+ previous infection ~ x3 Vaccine

Scientists theorized that either Delta would evolve more immune evasive mutations or a totally new variant would arise. However, I didn’t think it would spread this quickly.

What is the impact?

Therapies. Most antibody therapies are directed as the business end of the spike protein—the receptor binding domain (RBD). The rest of the protein is covered in glycosylation modifications that block much recognition. Thus with many mutations in Omicron compared to the wild type strain (white), most therapeutic antibodies no longer bind/ inactivate viral replication.

Source: https://biorxiv.org/content/10.1101/2021.12.12.472269v1.full.pdf

Only one monoclonal antibody—Sotrovimab from GSK—is effective, because it binds a pan-coronovirus epitope outside of the RBD. However, this antibody is in short supply.

  • Thus, knowing which variant someone has can direct therapy. Several hospitals in our area are out of Sotrovimab, and only people with the Delta variant can access other options. Thus, knowing the variant in a short time frame has clinical implications.
  • Whole genome sequencing takes too long, so the FDA has agreed to review PCR genotyping approaches for clinical use. I have described some previous approaches, but many of these methods are useful as a screening method and would not have sufficient specificity to determine whether an omicron variant is present. Next time, I will discuss variant genotyping, why it is important, how it can be done, and what clinical actions can be taken with the knowledge.

Severity. There are signs that it is less severe. Is this due to increase in immune tolerance? We now have been prepared by either previous infection or vaccination to be protected from hospitalization or severe disease.

@Jburnmurdoch https://twitter.com/jburnmurdoch/status/1478339769646166019/photo/1

Or is the decline in severity due to lower pathogenicity? A recent non-peer reviewed study indicates the virus replicates x70 faster than Delta in the upper airways (left), but infiltrates cells 10% as well as the original strain.

From: https://www.med.hku.hk/en/news/press/20211215-omicron-sars-cov-2-infection?utm_medium=social&utm_source=twitter&utm_campaign=press_release

We all hope this will continue to be better news about the severity of Omicron, but from the lab side, I’ve heard of positivity rates >50% at some places. So this can still have a broad impact.

-Jeff SoRelle, MD is Assistant Professor of Pathology at the University of Texas Southwestern Medical Center in Dallas, TX working in the Next Generation Sequencing lab. His research interests include the genetics of allergy, COVID-19 variant sequencing, and lab medicine of transgender healthcare. Follow him on Twitter @Jeff_SoRelle.

Where have all the Techs Gone?

Electronic media is replete with articles and editorials of employers lamenting the shortage of workers. Signs offering hiring bonuses hang outside of restaurants, stores, and other retail outlets all across the country.

The inability to find workers has forced employers to take another look at their business model and reevaluate whether the model is still viable in its current form. The power balance in the employer/ employee dynamic has shifted. Employers accustomed to having their choice of applicants now find themselves scrambling to find workers.

No schools, No students

The healthcare industry, including the medical laboratory, is not exempt from the shortage despite healthcare experts and administrators knowing that the trending laboratory employee shortage was inevitable years ago.

Laboratory school administrators and managers have been sounding the alarm about the lack of community college and university medical technology program applications. Many academic medical technology programs are shuttered due to a lack of students.  The decrease in the number of students going into the laboratory field and the normal attrition rate of older workers retiring or moving on to higher-paying occupations has led to a high vacancy rate and a loss of expertise.

Burnout

The pandemic has added more pressure on a cohort of employees experiencing the stress of a new and unknown danger. These allied health professionals were (and are) the front-line response to a disease threatening everyone, regardless of economic or social demographics. Lab worker burnout has become a documented phenomenon

We call them heroes, but in reality, these are the same people working every day (pandemic or not), serving patients and delivering quality test results. Labs across the nation are filled with these everyday people. But just like everyone, laboratory workers have families, feelings, and needs they are trying to meet while being asked to give a little more. Many have little left to give and are now leaving the field to pursue other less stressful occupations or to simply enjoy the life they have worked so hard to build.

Start recruiting early

How can healthcare organizations stem the tide of those choosing to leave the lab and simultaneously attract young fresh minds to the unglamorous and less financially rewarding but necessary field of laboratory testing?

Presentations to elementary school children are a great way to introduce the next generation to the laboratory field. What child doesn’t like looking into a microscope to see their own red and white blood cells? Roadshows put on in junior high and high schools are a great way to kindle interest in healthcare just when students are beginning to ponder the question of what they want as a career.

Educational Aid

The cost of college continues to rise. Scholarships are often garnered by high-performing “A” students. But there is a pool of “B” students that could also benefit from financial assistance and would be just as welcomed into clinical laboratories. Broadening and diversifying the qualifications to receive a scholarship and financial aid could conceivably add to the pool of potential laboratory workers. Another unique idea is to allow laboratory workers’ dependents access to unused employee educational benefits.

Wellness in the Lab

Resources should also be dedicated to retaining technicians and technologists who are considering leaving the laboratory field.  The level of compensation is meaningful, but studies have shown that employees often leave the job for more esoteric reasons. Reducing stress, supporting a culture of wellness, inclusiveness, and belonging can differentiate one workplace from another. The theme of workplace wellness was extensively discussed at this year’s ASCP 2021 annual meeting in Boston.

The Need is Real

The pandemic has highlighted the importance of the laboratory to the health of the nation. The medical laboratory should use this moment in the spotlight to advocate for more resources and emphasize the necessity for more laboratory programs and students to meet the future testing needs of the nation.

Of course, many lab managers are wondering what to do today to stem the slow leak of personnel. Providing mental health support and financial incentives do work to keep these knowledgeable workers in the lab. Managers realize that laboratory science is a demanding high acuity job with little or no margin for error. To maintain quality, the healthcare industry will need to change its perceptions about the laboratory and address the lack of technicians and technologists with the same interest and retention resources given to nurses and doctors.

-Darryl Elzie, PsyD, MHA, MT(ASCP), CQA(ASQ), has been an ASCP Medical Technologist for over 30 years and has been performing CAP inspections for 15+ years. Dr. Elzie provides laboratory quality oversight for four hospitals, one ambulatory care center, and supports laboratory quality initiatives throughout the Sentara Healthcare system.

Disruption in Cancer Care: Good or Bad … What’s Next?

The concept of disruption often has negative connotations. Everyone on the planet can understand the phrase, “COVID-19 has disrupted our lives” without explanation. Although this disruption has been global, the disruption and ensuing impact this has had on non-COVID-19 related healthcare and, specifically, oncology, have been dramatic.

Surgeries, chemotherapy and other medical treatments were canceled or delayed by months, and volumes of testing across the cancer landscape dropped to minimums. Existing infrastructure furthered the deployment of telehealth consultations and, eventually, clinics were reopened; however, there is no question that many people with cancer face being diagnosed at a more advanced stage of disease, with worse outcomes.

On 25-26 October, the World Cancer Leaders’ Summit, organized by the Union for International Cancer Control and hosted by the American Society for Clinical Pathology, brought together more than 600 leaders from some 100 countries. One of the major topics of discussion was, “What do we do for oncology after COVID-19?”

In addition to examining heart-wrenching data on disruptions to cancer services, there were also positive discussions about what we have learned from this pandemic, how we have adapted, and what novel approaches we should keep that could create optimal, more efficient, or more impactful cancer care.

The positive side of disruption

When applied to innovative technologies or ways of thinking, “disruption” can be positive, particularly when we consider the many advancements happening so quickly with treatments, including immunotherapies like check-point inhibitors, mRNA cancer vaccines, CAR-T therapy, epigenetic therapies, that the different members of the cancer community are often running to catch up.

Some of these advances are simply operational efficiency (i.e., getting more output from the system by improving the inputs and the usage) while many are transformative innovations (i.e., immunotherapy for lung cancer and melanoma). And some advances are considered “disruptive” because they are not just a new way of doing something better but allow an entirely new approach that previously wasn’t available and that radically improves prevention, diagnosis, treatment or supportive care.

A disruptive revolution in cancer detection

In oncology, a true disruptive innovation is taking place with universal cancer screening (UCS) or multi-cancer early detection (MCED). The earlier a cancer is detected and the patient can start treatment, the higher the chance of survival. The current paradigm for cancer care is suspicion of cancer leads to diagnosis, which leads to treatment. Suspicion rests in either the results of a screening test or when a person shows symptoms, and diagnosis involves a biopsy that must be analyzed.

Primary care doctors and not just oncologists will be able to use UCS and MCED testing platforms. Tests will be performed on a timescale (e.g. annually, every five years) relevant to the person’s age, medical and family history as well as the type of cancer being detected for, rather than wait for a patient to present with symptoms. Furthermore, these platforms will be able to detect 20 to 50 or more cancers from a single sample and for myriad cancer stages, including precursor or pre-invasive cancer, and there is no need for a separate diagnostics phase: the result itself would dictate a treatment because the UCS/MCED platforms not only detect the cancer but can, in theory, give an origin and medical response parameters.

Whereas the current paradigm involves primary care, oncology, surgery, radiology, pathology, nursing, etc., this new paradigm would only involve primary care and an insurance provider.

Innovating, Creating and Breaking Down Barriers

The transition from traditional oncology to such novel platforms – as with all disruptive technologies – will not be smooth as we are talking about entire businesses and careers connected to traditional oncology possibly become obsolete. People with cancer, however, are expected to have shorter, more efficient journeys, likely with better outcomes and at a lower cost.

In LMICs, where oncology care systems are not nearly as developed as in HICs and where governments, unlike the US, are generally assumed or expected to pay for cancer services, UCS/MCED will require fewer dollars and provide better results than investing in the infrastructure required to create traditional cancer care systems. If this theoretical framework (UCS/MCED for cancer) does demonstrate the value in promises, it would set the stage for similar paradigms in other non-communicable diseases for which infrastructure and resources in LMICs are often lacking.

UCS/MCED was a hot topic at the WCLS. The leaders that were involved in the meeting sit on either side of a fence with regards to this innovation. There are those that support this technology’s development as quickly as possible, anticipating better patient outcomes, more efficient systems, less healthcare spending and more revenue. There are also opponents to this innovation, who throw up barriers resulting from fear of losses (revenue, employment, testing volume, referral networks, etc.).

The barriers they present, however, are important only if they are true barriers and not just perceived barriers. Why? True barriers are likely to require the engagement of the traditional oncology system to overcome; yet the act of overcoming those barriers may herald the disruptive innovation they fear. When an existing system must participate in its own creative destruction, can such a disruptive innovation take place?

No doubt the participants of the WCLS will continue to ask this question and let’s hope they find some answers for the sake of our patients.

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-Dan Milner, MD, MSc, spent 10 years at Harvard where he taught pathology, microbiology, and infectious disease. He began working in Africa in 1997 as a medical student and has built an international reputation as an expert in cerebral malaria. In his current role as Chief Medical officer of ASCP, he leads all PEPFAR activities as well as the Partners for Cancer Diagnosis and Treatment in Africa Initiative.

E(cto)pic Metastasis

A 72 year old female originally presented with lung carcinoid and bilateral renal masses. The patient’s left kidney biopsy demonstrated ectopic thyroid parenchyma by an outside institution. Her thyroid function tests were unremarkable, she had no known previous head and neck radiation, and to the best of her knowledge, there was no family history of thyroid cancer. She underwent FDG PET imaging, which showed increased bilateral uptake in the neck (thyroid and lymph nodes), and an avid right posterior renal mass. Otherwise, her scan was relatively clear. Her left renal mass was resected and demonstrated thyroid parenchyma, but the differential diagnoses included thyroid heterotopia and metastatic well-differentiated thyroid carcinoma.

FNA and core biopsy were then obtained from the right upper quadrant of the kidney. The findings are depicted below.

Images 1-6: Kidney, Right, Fine Needle Aspiration. 1: Pap-stained smear; 2: DQ-stained smear; 3: H&E Cell Block section; 4: TTF-1+; 5: Thyroglobulin +; 6: CK7+.

The FNA was signed out as “Atypical thyroid tissue present.” Immunohistochemical stains demonstrated positive staining for CK7, vimentin (partial), TTF-1, thyroglobulin, and PAX-8 (partial), and negative staining for RCC, Napsin A, synaptophysin, and chromogranin. While these immunostains suggest thyroid-type tissue, morphology was most worrisome for metastatic thyroid carcinoma. The chromatin presented as hypochromatic and powdery, nuclear grooves and pseudoinclusions were present, and the nuclei were enlarged with irregular membranes. However, the scant material present precluded a definitive diagnosis.

Images 7-8: Kidney, Right, Core Biopsy. 7, H&E section 100X; 8, H&E section 400X.

The core biopsy suggested benign-appearing thyroid tissue similar to that seen in the left kidney, however, the surgical pathologist diagnosed the material as metastatic thyroid carcinoma.

A thyroid FNA was obtained from one of the patient’s multiple right-lobed thyroid nodules consistent with TI-RADS category 5 the next day. This was diagnosed as atypia of underdetermined significance due to scant cellularity.

Images 9-10: Thyroid, Right Lobe, Fine Needle Aspiration. 9: DQ-stained smear; 10: Pap-stained smear.

The right renal mass was resected after molecular profiling was performed on the left renal mass tissue. Mutation Detection by Next Generation Sequencing demonstrated a tumor mutation burden of 3.6Muts/Mb and identified mutations in the PRKDC, PTEN, and KRAS genes. Two kidney tumors were identified in the right kidney (one measuring 8.0 cm and the other 4.5 cm), both diagnosed as metastatic thyroid carcinoma with papillary features.

Images 11-12: Kidney, Right, Resection. 11, H&E section 40X; 12, H&E section 400X.

The thyroid was then resected, and pathologic findings were consistent with invasive follicular carcinoma with extensive angioinvasion to 4 or more vessels. While renal metastases are rare, the high affinity for angioinvasion makes the kidney a prime metastasis site due to its vascular-rich tissue. The patient was prescribed a low iodine diet and Thyrogen-stimulated radioiodine ablation to remove any remaining thyroid tissue or micrometastases and enhance the sensitivity of thyroglobulin as a tumor marker for surveillance purposes. While thyroid cancer (papillary and follicular types) is typically considered “the best cancer to have” due its slow growth and low-risk of widespread malignancy, it doesn’t mean that it won’t metastasize, even to a distant organ that you normally wouldn’t suspect. Great caution must be taken to ensure that lumps, bumps, and swallowing issues are addressed at annual physicals to catch a low-risk cancer before it has the opportunity to become an epic metastasis.

-Taryn Waraksa, MS, SCT(ASCP)CM, CT(IAC), has worked as a cytotechnologist at Fox Chase Cancer Center, in Philadelphia, Pennsylvania, since earning her master’s degree from Thomas Jefferson University in 2014. She is an ASCP board-certified Specialist in Cytotechnology with an additional certification by the International Academy of Cytology (IAC). She is also a 2020 ASCP 40 Under Forty Honoree.

Moving Beyond Data to Action

On October 6th, 2021, the Lancet Commission on Diagnostics launched the “Transforming access to diagnostics” commission report with a virtual program and release of several publications. One of the publications included a study led by Dr. Sue Horton on access to diagnostics using data from 14 countries, mostly in Africa, from 2004 to 2018 with single timepoint data used to evaluate the relationship of access to diagnosis with a variety of factors. The diagnostics that were evaluated did not include histopathology, crucial for the diagnosis of cancer; however, the study did show importantly that income and population density had demonstrable relationships with access to diagnostics at the primary care level. For hospital-based access, there was no relationship which led the authors to conclude, among many other and relevant points, that access to diagnostics in “primary health care is the diagnostic so-called last mile and particularly affects poor, rural, and marginali[z]ed communities globally; appropriate access is essential for equity and social justice.” In the Commission report, the authors describe a tiered system with three levels that countries should incorporate into a national laboratory strategy and suggest that the burden of affording this system should fall on the governments. Moreover, they demonstrate the extremely important data around use of global markets to show that while the top four countries supply nearly 50% of all diagnostics, those same four countries only supply 24% of pharmaceuticals. In the opening statements to the Lancet Commission launch, Dr. John Nkengasong espoused very strongly the importance of manufacture of diagnostics WITHIN LMICs as one much needed solution.

For example, I was assisting a colleague with access to immunohistochemistry antibodies for which they were currently paying $700 USD for one vial of CD20. I traced the manufacture back to the US supplier (where the antibody was produced) and attempted to buy a vial as a private citizen with a credit card and was surprised to see that I could do so for $220 USD. This is the exact same vial of CD20 antibody. Why was my colleague paying a 218% markup? When I inquired with the company of manufacture, they reported that they had existing contracts to supply 2nd, 3rd, and 4th party vendors that they could not violate (i.e., they could not sell directly to a purchaser on the continent of Africa). The local supplier charging the $700 USD suppled a very large number and breadth of medical supplies including other diagnostic tests and reagents. Those reagents were reasonably priced, and several were on sustained government contracts. However, the CD20 antibody was not. Why is that the case? Let’s assume you are a supplier of widgets and wobbles. Your demand for widgets is huge and you sell more than 100,000 widgets per month to 20 different consumers. For wobbles, one person orders one wobble once per year. Your widgets ship room temperature but your wobbles require a cold chain, lest they be destroyed. What would you do? You could choose not to sell wobbles. You could choose to charge a ridiculous price for wobbles so that the excess time, energy, and expense of getting one wobble to your consumer is worth the effort. But you would not sell the wobbles for a similar profit margin as your widgets. It just wouldn’t make business since. Now imagine that the wobbles are manufactured in a country other than your own and to get them, you buy them from a country supplier who buys them from a regional supplier. So, wobbles already come with additional markups. You do have a third choice which is to manufacture wobbles locally, cut out the middle people, and charge much less but still make more profit. This is a great model if wobbles can be easily manufactured; however, when wobbles require an enormous capital investment, is it worth it to sell a couple of wobbles a year? Of course not. This business-based example is one of the drivers for a $700 USD vial of CD20. If a local manufacturer, in country or in a neighboring country, could manufacture and sell, this reagent would be more affordable and feasible as an available diagnostic. Specifically, patients with lymphoma would have access to rituximab for CD20.

But note the Commissions finding that almost 50% of diagnostics are made in the top 4 countries. This means, naturally, that the pricing for these reagents and supplies will be based on that economy and/or GDP, not on the economy or GDP of every country down to the lowest on any given scale. Consider the Big Mac Index, which looks at buying power relative to the US dollar. The only African country used in the Big Mac Index is South Africa and it is third from the bottom. To be clearer, if you have 100 South African Rand, you could get about $6.69 USD if you exchanged it directly (ignoring fees). If you want to buy a Big Mac in the USA, the average consumer price is $5.65; however, in South Africa, it’s 33.50 Rand. Based on the Dollar:Rand exchange rate, we are paying only $2.24 USD in South Africa for the same sandwich that would cost us $5.65 in the US. So, the Rand is undervalued. Now, let’s look at our vial of CD20 (not revealing the country to protect identities). According to the current exchange rate, you get $4.34 USD for every 10,000 units of this countries currency. Based on this model, if the CD20 was being EVENLY exchanged with cash (as opposed to being undervalued or discounted as we saw with South Africa), it should cost 450,586 units of this country’s currency. Instead, it is costing them 1,612,053 units. If we assume that this country could/should achieve a Big Mac Index equivalent discounted of the CD20 as we see with the Big Mac itself in South Africa, it should cost them 307,057 units or $133 USD. The difference? The Big Mac is manufactured and locally distributed directly to the customer in South Africa. The CD20 is not. So, one step to achieving an equitable pricing structure in healthcare for LMICs, especially in Africa, needs either direct discounted by US- and European-based manufacturers—unlikely to occur because of fear of alternative market access—or these products need to be manufactured and supplied locally.

What I have trouble agreeing with completely and, in some cases, even it part, is the concept of all healthcare costs falling on the government of a population with the expectation that they deploy a “one size fits all” approach to any aspect of healthcare. When we consider the US and Europe (again, the top four producers of diagnostics), we find one as a largely private commercial system driven by government pricing for elder care and the other a socialist system with universal healthcare enhanced by private care. For both systems, there is a huge economic base which either drives capitalism across the system from raw materials to final product or an enormous tax base that can cover the bulk of the costs of the systems. As we move from these four down the GDP ladder to LMICs, we don’t see, despite that we would like to nicely categorize countries into clear groups, a solution that would work “globally” because major pieces of economic development are needed as pre-requisites for a capitalist open market or one payer system. Each country has a unique set of circumstances (e.g., history, genetic diversity, geography, natural resources, tourism, disease burden, language, population size, etc.) that cannot be reduced to simply a GDP value or Big Mac Index factor. Moreover, it is wholly within the realm of colonialism, which we supposedly abandoned 70 to 80 years ago, to think that we can propose a system for “all countries” that would even remotely approach the solving the problems of these countries. Although it is an excellent mental exercise to idealize a healthcare system as having something as simple as three tiers and trying to allocate what tools and resources are needed at each level to accommodate the population, the reality is that such a framework is only a starting point with a lot of work needed to fully realize what type of system would be best for a given country. Very small islands and small nations may have only one hospital to serve its entire population and insufficient patients of a given type to justify the expense of certain tools. Extremely large countries with large populations will need a myriad of systems with their own tiers that support patients based on location, socioeconomic status, language, etc. and these systems likely overlap in geography. And the expertise to best determine that system is the health and government leadership of that country, not an external set of non-specific instructions. The external set of instructions, however, are extremely important, as noted, as a starting point, but each country that identifies a gap in their diagnostics, for example, has to assess their specific situation. At the heart of this problem is the need to stop talking about the challenges of global healthcare and start (or continue) directly working on fixing them.

At ASCP, we approach our global outreach through assessment, gap identification, implementation planning, and execution (AGIE). Through that approach, we have deployed and/or support 19 sites in 15 countries with telepathology; however, in an additional 10 countries, we have active programs that have not yet reached a point of telepathology deployment. Had we said, from the beginning, “We are going to give everyone telepathology”, we would have wasted an enormous amount of time and money. By following an AGIE approach, we have navigated to the specific problems of each site with whom we collaborate and attempted to solve them. And we do so with more than 80 collaborative partners. The Lancet Commissions on Diagnostics most recent launch is an excellent first alert for those who have not been engaged in global health for the last 20 years that there are still major challenges and problems in global healthcare and diagnostics. Our hope is that funders, governments, industry, health system members, patients, and advocates will view this as a rallying cry to direct resources and energy to join those of us who have been engaged in this work to move the needle even further. Access to diagnostics for every patient everywhere. It is ASCP’s simple mantra, and we hope, together, we can achieve that goal.

References

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-Dan Milner, MD, MSc, spent 10 years at Harvard where he taught pathology, microbiology, and infectious disease. He began working in Africa in 1997 as a medical student and has built an international reputation as an expert in cerebral malaria. In his current role as Chief Medical officer of ASCP, he leads all PEPFAR activities as well as the Partners for Cancer Diagnosis and Treatment in Africa Initiative.

The Anatomy of Lab Safety Design: Handling a Flood

Most laboratories are designed with eyewash stations and at least one safety shower depending on the size of the department. The use of these safety showers is not common, but it does happen, and the staff needs to be prepared for such an event. That preparation not only involves testing and training on equipment use, but also in making sure the physical space is ready for a potential deluge of water that can pour down into the department for potentially up to fifteen minutes. Other flooding incidents may occur as well. A floor drain can back up, a water line connected to an analyzer might break, or water might even come through the ceiling from a pipe above the department. Being prepared and responding efficiently to these types of flooding events should be part of the overall lab safety program.

One reason safety specialists and some regulatory agencies require that items in the lab not be stored directly on the floor is so they will not be damaged in the event of a departmental flood. It is generally acceptable to store plastic items (waste bins, etc.) on the floor since they cannot be damaged by water. Cardboard, computer hard drives, and other like items should be stored on palettes or shelves. Securing electrical wires and raising multi-plug adaptors off the floor is also a best practice.

When designing or remodeling a laboratory, consider the possibility of floods when choosing the type of flooring to be installed. The best laboratory flooring is monolithic, like a sheet vinyl that has few seams. It should bend up to the walls to create a coved base that is integral with the floor. This design (recommended by the CDC and CLSI) keeps liquids from going under tiles or through walls which will create more problems (like mold) down the road.

Floor drains where safety showers exist are not required, and many labs have showers where there is no drain at all. Remember that in a typical situation where a shower would be used, hazardous chemicals are involved. Any hazardous waste that might go into the sanitary sewer should be routed through a neutralization station or into a hazardous waste collection tank. The ANSI requirements for a safety shower include the ability to deliver 20 gallons of water per minute for 15-20 minutes. That’s a total of 400 gallons. The requirements also state that the water pattern must be at least 20” in diameter and 60” above the floor. Therefore, a majority of the water will not even travel to the drain. It will go to the lowest point of the floor in the department. The bottom line is, if the safety shower must be used, a flood should be expected.

In order for the lab to be prepared for a flood emergency, materials should be on hand that will help contain large amounts of water. Those materials may include large volume spill kits with booms or dikes that are capable of holding water back. Staff should be trained how to use these materials as spill training is provided, and drills should be conducted so they can use the supplies comfortably. Make sure these spill materials are easily accessible and that signage clearly indicates where they are stored.

What does the physical anatomy of your lab look like? Is it designed for safety in the event of a hazardous material spill or exposure? Is the department set up to handle a sudden flood situation, and can staff identify the steps to take to respond efficiently and safely? Take a look around your lab today, and make any necessary corrections so that all will be ready should a laboratory flood occur for any reason.

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.

Looking into the Pathology Mirror

Conversing with people early in their career has always been an exciting experience for me and, I hope, for those with whom I have spoken. I tend to get enthusiastic in discussing all the possibilities that lie ahead and try to keep the conversation focused on the individual in question. I try to avoid talking about my own career path unless someone specifically asks—but I keep it brief. One-on-one conversations tend to be very productive for the individual because we can delve deep into their questions, fears, concerns, hopes, and goals. Group discussions often end up being more informative for me, and I have learned a ton from listening to dynamic young people. I was recently gifted with the opportunity to lead 9 focus groups as part of a grant-funded project which included several groups with medical students and pathology residents. Although our focus was on forensic pathology, the groups were quite diverse. I would call the experience overall very positive and enlightening for all of us, but I was struck by a few observations that I felt the need to explore further on my own—so, you get to read a blog about it.

Pathology is a fascinating specialty after medical school that covers a large range of diseases and patient types, an even larger range of scopes of practice, and includes some of the lowest and highest paid jobs in the field. At the same time, the practices of pathology and medicine are evolving at an extremely rapid rate while medical knowledge is expanding exponentially. There is an entire industry based around paraphrasing the current literature for a given specialty because, even within a specialty, you can’t read every new study or follow every new development. It is this expansion that has created the demand by pathologists in the last 2 decades to be sub-specialists so that a focus on one particular area of practice will keep their expertise sharp, their diagnoses hyper-accurate, and their risk profile minimal. This expansive phenomenon in medicine in general but specifically in pathology is an excellent indicator that the field of knowledge is ripe for a disruptive innovation. It is common knowledge that the practice of anatomic pathology, for example, is based on a technique that is more than 100 years old—histology; however, what is not common knowledge is that the amount of data generated by reviewing a histology slide from, for example, a tumor, is 1/1000th or less than the data generated by performing genetic sequencing of that same tumor. Add to the mix the ability to perform transcriptional analysis, mass spectroscopy, metabolomics, lipidomics, phospholipidomics, glycobiological analysis, etc. and it becomes clear that what is contributed by an H&E pales in comparison to what we can know about a piece of tissue. There are barriers, you say? Cost, integration of information, usable outputs, or process:volume ratios? All true. But the technological ability to characterize a tumor across all these different attributes and mathematically reduce that to a multiplex assay which can perfectly classify and predict therapeutic responsiveness exists. Still don’t believe me? A collection of companies is focused on testing that has been variably called, “Universal Cancer Screening”, “Multi-cancer Screening”, and “Multi-cancer Early Detection”. These systems currently use sequencing across multiple loci to detect from 20 to 50 different cancer types. One such company can do so with stool to look for gastrointestinal cancer and is on the market today. Why am I going down this path of which many of you are already aware? Because when I was talking to a trainee recently, they told me that they originally wanted to go into forensic pathology but were talked out of it and were now considering doing GI pathology. Let’s break this down so you can understand my frustration.

GI pathology as a career is largely generating revenue through colonoscopy from screening. Yes, the field is diverse and the most complicated parts like liver, pancreas, IBD, etc. are part and parcel to the practice. But, from a C-suite perspective, the fiscal bulk of the value of the service is in biopsy reads from screening. Because of the interest in the field in the last two decades (increase in pathologists in GI) juxtaposed to the much-needed control and reduction of 88305 reimbursement (due to rampant misuse and overuse), there are a lot of GI pathologists in the United States. So many, in fact, that jobs for GI pathology are sort of hard to find. Add to the mix a product, already on the market, that can detect colon cancer in stool without screening colonoscopy and its risks, which is only the harbinger of a group of products that will arrive on the market which can do the same for many other cancers from stool, blood, etc., and one gets nervous about where GI pathology’s current revenue volume is headed. But then there is the recent recommendation that the screening age for colonoscopy be reduced to 45 (from 50). The increase in volume of biopsies from screening (if everyone was 100% compliant) would overwhelm some practices. Where is GI pathology as a specialty going? Do we have too many and should we be concerned about disruptive innovations to screening decimating revenue generating volumes? Or are we facing an overwhelming number of biopsies with the new screening guidelines? I wouldn’t dare try to predict where this is headed but there is clearly some “uncertainty” in the practice of GI pathology. And a practicing pathologist talked a resident out of forensics and into GI??

Let’s contrast this with forensic pathology so my point is clear. There are currently only about 500 FPs in the United States and there is a need—to meet minimum requirements for coverage—of 1200 FPS. That’s a difference of 700 FPs, all of which must be board certified pathologists. There are more than 50 current open full-time positions for FPs that are funded (i.e., actively recruiting to hire today) that were identified on the most common sites for these listings. Seven of these programs offer tuition repayment for FPs from $100,000 to $250,000. Outside of those seven programs, there are three federal programs that specifically offer loan repayment for FPs and a fourth for which they are also eligible. Doing the math, basically, anyone wanting to practice forensic pathology likely qualifies for a loan repayment program (hint: that’s not true for the majority of pathology jobs). Although the average salary for an FP is often reported as ~$110,000 (about half of the average salary for a pathologist according to publicly available data), the current open positions I mentioned have an average of $240,612 (with a range of $175,000 to $350,000). The work of forensic pathologists includes death scene investigation, varying levels of postmortem examination (e.g., chart review, external examination, complete autopsy, etc.), medicolegal reporting including court appearances, participation in public health investigations, participation with local government, etc. This role is vital to the functioning of society and is required by law to be performed. Stated another way, we will always need FP (and we desperately need them now!). It is very difficult to imagine a disruptive innovation or even a transformative innovation that will replace this role in the next several decades. That same can’t be said for other parts of pathology (see my GI example above). And yet, we struggle to find FPs. Why?

Certainly not the only reason but a valid and real reason that we struggle is the presence of microaggressions in the medical community. These are common for pathology in general but can be extremely harsh and rampant for forensics (even coming from other pathologists!). The real example I have given you of the resident selecting GI after being talked out of forensics is a true story. And, more importantly, it was reiterated by nearly every medical student and resident (and fellow) with whom we talked about their experiences. Considers these statements (which are direct quotes):

“You’re too smart to do pathology.”

“Why would you waste your brain on forensics?”

“You’re too good with people and patients to be a pathologist.”

“Forensics is a dead specialty (pardon the pun)”.

Excuse me?? Are you kidding? It’s not that these microaggressions are inappropriate because they are damaging to a young person’s passions and interests. It is that these microaggressions, which are heard repeatedly, are simply wrong. Pathology, if nothing else, is a data and knowledge heavy specialty where we spend most of our time thinking, solving problems, and receiving, processing, interpreting, and synthesizing data into a useful answer on which a clinician can act. And we don’t do it one patient at a time. We produce literally thousands if not tens of thousands of tests results per day in an average laboratory. Forensics requires highly intelligent, detail-oriented individuals who can not only synthesize an entire patient’s life and death into a succinct story—but they have to defend their opinion in court. Every day! I’d like you to ask your primary care doctor if every decision he/she made for each of their patients in one day they would be comfortable defending in court. Every decision! It requires a special person who is not only amazing with data and knowledge but extremely talented at interacting with people—many of which are trying to prove you wrong. Moreover, few medical specialties call upon the physician to routinely deal with families at the lowest point in their lives in every single encounter. A person that is good with people and patients is exactly the person that can become a successful forensic pathologist—one that provides meaningful care when care is most needed. And lastly, forensics is thriving as a job market (as I described). And yet, our “mentors” who train our medical students and pathology residents continue to provide microaggressions (or outright rebuke) for those brave, brilliant individuals who would choose forensics as a career. Considering the state of the field and the perks of the practice at the moment, forensics seems like a pretty smart choice today. But stepping back from this rhetoric to a 10,000 foot view—because, remember, this is me thinking through a problem and forcing you to read about it—the overall observation I have is that the field of pathology (internally) needs to understand where it is going, what its scope of practice will look like tomorrow, 5 years, and 10 years from now, and, more importantly, what the needs of our patient community are (alive or dead). Without a global view of the total need in pathology, how can we possibly have meaningful conversations with individuals early in their career that both enhance their passion and meet the needs of the community of practice?

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-Dan Milner, MD, MSc, spent 10 years at Harvard where he taught pathology, microbiology, and infectious disease. He began working in Africa in 1997 as a medical student and has built an international reputation as an expert in cerebral malaria. In his current role as Chief Medical officer of ASCP, he leads all PEPFAR activities as well as the Partners for Cancer Diagnosis and Treatment in Africa Initiative.