Microbiology Case Study: A 55 Year Old Male with Altered Mental Status

Case History

A 55 year old male presented to the emergency department (ED) with altered mental status (AMS). His past medical history includes stage 4 pancreatic cancer with known invasion into the distal splenic vein. Currently undergoing chemotherapy, his last infusion was one week prior to presentation. On physical exam, the patient is a cachectic male with dry mucous membranes, scleral icterus, hypotension (79/37), hypothermia (35o C), tachypnea (Respiratory Rate of 20/min) and tachycardia (pulse up to 130s). Initial labs were ordered including blood cultures and were significant for hypoglycemia (40mg/dL), pancytopenia, mild liver function test abnormalities, an ammonia level of 80 µmol/L and lactate of 11.2 mmol/L. It was concluded that the AMS resulted as a consequence of hypoglycemia. However, there was also concern for intracranial pathology vs. stroke vs. metastatic disease. Brain imaging showed no obvious lesion or mass. The cause of the hypotension was uncertain but could be a result of volume depletion or sepsis. Empiric vancomycin and cefepime were initiated in the ED. However, the patient decompensated, developing mid-abdominal and periumbilical ecchymoses suspicious for a retroperitoneal hemorrhage. Despite aggressive therapy, he expired in the ED.

Laboratory Identification

An anaerobic blood culture bottle flagged positive at 5 hours incubation. A gram stain showed large, boxy, gram positive rods without spores (Image 1). Brucella blood agar was inoculated and incubated anaerobically.  Following overnight incubation, the surface of the plate showed a subtle film of growth covering the plate and detectable hemolysis (Image 2). No discreet colonies were identified. A catalase test was performed and was negative. Definitive identification of Clostridium septicum was obtained by MALDI-TOF.

Image 1. Gram stain from the anaerobic blood culture bottle that flagged as positive following 5 hours of incubation. Boxy, large gram positive rods without spores are observed. Oil immersion photomicrograph (x100 objective).
Image 2. Brucella agar plate following 24 hours of incubation under anaerobic conditions at 35oC. Significant bacterial growth in a haze and detectable Beta hemolysis can be observed. No discreet colonies can be identified. Identification by MALDI-TOF was Clostridium septicum.

Discussion

Clostridium septicum is an anaerobic gram positive bacillus that can produce spores; however, spores are not frequently seen, especially in nutrient-rich environments. Spores, when present, are typically oval and located subterminally. Infection by C. septicum was once thought to be extremely rare, but improvements in anaerobic laboratory techniques have allowed for the discovery of the true potential of this agent. C. septicum is one of several bacteria that can cause myonecrosis (i.e., gas gangrene). Infections are typically seen in settings of immunodeficiency, trauma, surgery, malignancy, skin infections/burns, and septic abortions. The colon may promote the growth of C. septicum better than other anatomic sites due to its anaerobic conditions. As one of the more aggressive etiologies of gas gangreneC. septicum infection progresses very rapidly, with a mortality rate of approximately 79% in adults, typically occurring within 48 hours of infection. Symptoms of infection include pain, described as a heaviness or pressure that is disproportionate to physical findings, tachycardia, and hypotension. Tissue necrosis then causes edema and ischemia resulting in metabolic acidosis, fever, and renal failure. The carbon dioxide and hydrogen produced during the growth of the organism move through tissue planes, causing their separation, producing features characteristic of palpable emphysema (i.e., crepitus). This also results in a magenta-bronze skin discoloration and bulla filled with a foul-smelling serosanguinous fluid.

Four toxins have been isolated from C. septicum: the lethal alpha toxin, DNase beta-toxin, hyaluronidase gamma toxin, and the thiol-activated/septicolysin delta toxin. Alpha toxin causes intravascular hemolysis and tissue necrosis and is well known as the primary virulence factor of C. septicum

C. septicum derived gas gangrene has shown strong correlations with increased levels of malignancy. Patients with C. septicum infections may have an occult colon cancer or a tumor that has metastasized to the colon. C. septicum bacteremia is also associated with typhlitis (defined as inflammation of the cecum that can extend proximally into the terminal ileum or distally into the ascending colon), which can develop in patients with hematologic malignancy receiving chemotherapy. Because the organism may be harbored in the gastrointestinal tract, the organism may gain access to the bloodstream through the ileocecal region.

Therapy includes antibiotics and surgical debridement (with occasional amputation). For antibiotic selection, typical anaerobic coverage includes piperacillin/tazobactam, ampicillin/sulbactam, metronidazole or meropenem. Vancomycin is also effective. Susceptibility testing is not typically performed; moreover, the CLSI makes an annual antibiogram which can be used as a guide. 

Key points

  • C. septicum often has swarming growth that covers the plate surface.
  • Spontaneous myonecrosis with C. septicum bacteremia can be an indicator of possible occult colonic malignancy.
  • C. septicum can be associated with typhlitis in neutropenic patients with hematologic malignancy undergoing chemotherapy.

 References

  1. Smith-Slatas CL, Bourque M, and Salazar JC (2006). Clostridium septicum infections in children: a case report and review of the literature. Pediatrics 117(4): e796-e805.
  2. Alpern, RJ and Dowell, VR (1969). “Clostridium septicum infections and malignancy”. JAMA. 209: 385–388.
  3. Ballard, J, Crabtree, J, Roe, BA, and Tweten, RK (1995). “The primary structure of Clostridium septicum alpha-toxin exhibits similarity with that of Aeromonas hydrophila aerolysin”. Infection and Immunity. 63 (1):340–344.
  4. Sidhu JS, Mandal A, Virk J, and Gayam V (2019). “Early detection of colon cancer following incidental finding of Clostridium septicum bacteremia”. J Investig Med High Impact Case Rep. Jan-Dec;7:2324709619832050.
  5. Srivastava I, Aldape MJ, Bryant AE, and Stevens DL. (2017). “Spontaneous C. septicum gas gangrene: A literature review” Anaerobe. Dec;48:165-171

Xiang Xu, MD, PhD and Dominick Cavuoti, DO contributed to this case.

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

The NEXT Storm in Puerto Rico

In 2017, Puerto Rico had a very challenging year with both Hurricane Irma and Maria bombarding its shores. Just last month, Puerto Rico was spared a hit from Dorian. However, a major storm (of sorts) will be hitting Puerto Rico on September 30, 2019, regardless of what the weather says. On that day, the Section 2005 of the Affordable Care Act expires which provided PR with $5.4 Billion in Medicaid funding (from July 1, 2011 to September 30, 2019). If it were any other state of the United States, the expiration of this relief funding would not be such a challenge because of the current matching programs afforded to those states by the federal government. However, PR is unique in that it is only provided a block grant (i.e., a set amount of money) and that block grant is significantly lower than what other states get overall. Based on current estimations of costs in PR, the block grant funding will be exhausted by March 2020. At that point (well after hurricane season), PR will have to cover all costs for Medicaid for its citizens 100%. Why is that a problem?

In order to understand this, we have to look at PR’s healthcare system (removing the stress, strain, and destruction on the system delivered by Irma and Maria) in its base state. The public health care system in PR was privatized and now includes forced managed care participation. Of the 3 million citizens living in PR (which is on the decline), more than half are covered by Medicaid. The Medicaid eligibility limits in PR are much lower than other states ($6,600 in PR vs. $17,236) and with other states ability to expand coverage to 138% of the poverty line, PR can not go above 40% of the poverty line. This leaves a significant portion of the population ineligible. The cost of living in PR is actually higher than many mainland states while the average income is much lower. The per enrollee Medicaid benefit in PR is $2,144 compared with the lowest mainland state ($3,342) and the median state ($6,763) for projected 2020 budgets. If PR were afforded the same system of delegating funds from Medicaid to its enrolled citizens (i.e., matching based on income), the Medicaid matching rate would be 83%; however, because of the block grant the effective matching rate is between 15 and 20% for PR. Reimbursements for equivalent services in the mainland US are significant less in PR (for example, as low as $10 to a physician for an office visit). Unlike other mainland states, a US federal act (PROMESA) created an oversight board (FOMB) to manage the island’s finances and one of the main tools of the FOMB to control costs in PR has been to deeply cut Medicaid spending. 

Given that situation, it should not be surprising that prior to the 2017 crisis, healthcare professionals were leaving PR in large numbers and that trend increased after 2018. In an effort to stem this exodus, Act 14-2017 was enacted (February of 2017) which reduced certain physicians’ income tax in PR to 4% (down from 33%). This act went into effect in April of 2017 but data show physicians continue to leave, evidence that physicians value ability to care for their patients (i.e., resources to provide quality care) over their own income. Jennifer Gonzalez-Colon, the resident commissioner for PR (the only representative to Congress with limited voting rights and a marginalized role) introduced the Puerto Rico Integrity in Medicare Advantage Act in September of 2018 to stabilized Medicaid payments in PR following Maria (as an amendment to XVIII of the Social Security Act), which would have improved payments including to physician providers. The Act died in when the 115th Congress concluded in 2019 having never been enacted.

PR’s Medicaid program is, thus, in a crisis situation which will either need to be resolved before March 2020 or will result in potentially increased challenges (i.e., assuming additional healthcare professionals leave the island). With an already aging healthcare professional population (i.e., young professionals leave) and an aging population of patients, an enormous storm that has been brewing for years will be unleashed in the spring. The solution is for those controlling the healthcare finances of the island to create equitable systems of payment to support the US citizens of PR.

References

  1. Urban Institute Report – PR HC Infrastructure
  2. Revitalize Puerto Rico
  3. Judith Solomon on PR’s Medicaid Program
  4. Rick Shinto on Ending PR’s Health Care Crisis
  5. Caribbean Business June 2018 PR challenges
  6. Puerto Rico – Medicaid.gov
  7. Finding Health Insurance in PR
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.

Hematopathology Case Study: A 69 Year Old Male with Weight Loss and Generalized Lymphadenopathy

Case History

The patient is a 69 year old male who presented to the hospital with a 3-month history of drenching night sweats, weight loss, fatigue, and generalized lymphadenopathy. He also endorsed a very itchy rash all over his body. He denied smoking. There was no other relevant social or family history.

Physical examination confirmed diffuse lymphadenopathy, hepatosplenomegaly and a mild diffuse skin rash. Notably, there was a 2.5 cm level-1 lymph node palpated in the left neck. This was subsequently biopsied.

Biopsy

Biopsy of the level-1 neck lymph node revealed a 2.3 x 1.5 x 1.2 cm mass pink-tan and firm mass. Sectioning revealed a glossy white-tan cut surface. H&E staining revealed a polymorphic lymphocytic infiltrate of in the interfollicular zones. The infiltrating lymphocytes ranged from small to large cells with abundant cytoplasm, eosinophils, and plasma cells. There was also a notable increase in the number of high endothelial vessels lined by lymphocytes with irregular nuclear borders and clear cytoplasmic zones.

Image 1. Polymorphic infiltrate of small, mature appearing lymphocytes (A), with prominent blood vessels and clear cytoplasm (B). Most of these cells were CD3 positive T cells (C) with expanded CD21 positive FDC meshworks (D) and scattered CD30 positive immunoblasts (E)

Further characterization by immunohistochemical staining showed the majority of the interfollicular cells to be CD3 and CD5 expressing T cells. These were a mix of CD4 and CD8 positive cells but with marked CD4 predominance. CD7 appeared positive in a smaller population of T-cells compared to CD3 (consistent with loss of this pan-T-cell marker). Varying numbers of the interfollicular cells were positive for CD10, BCL-6, CXCL-13, and PD-1 with a strong positivity for ICOS, phenotypically consistent with an expansion of Tfh (T-follicular helper cell) cells.

Interspersed between the T cells were numerous CD20 positive cells with prominent nucleoli that also revealed CD30 positivity. CD21 staining revealed expanded follicular dendritic cell meshworks. EBER ISH was positive in a rare subset of cells. Kappa and lambda ISH showed an increased number of polytypic plasma cells.

Flow Cytometry showed the presence of a small population of T-cells that were CD4 positive but CD3 negative. There was no evidence of B-cell clonality. TCR-G PCR was positive.

A final diagnosis of Angioimmunoblastic T-cell lymphoma (AITL) was rendered.

Discussion

AITL is a relatively rare neoplasm of mature T follicular helper cells, representing about 1-2% of all non-Hodgkin lymphomas. It is; however, one of the more common subtypes of peripheral T-cell lymphomas, accounting for 15-30% of this subgroup. The condition was first reported in 1974 in Lancet as a non-neoplastic abnormal immune reaction1. It was first recognized as a distinct clinical entity in in 1994 in the Revised European American Lymphoma Classification2. The disease shows a geological preference to Europe (28.7%) over Asia (17.9%) and North America (16%). AITL occurs primarily in middle aged and elderly individuals and shows a slight predominance of males over females.

The disease has a strong association with EBV infection, but the neoplastic T-cells are almost always EBV negative, creating an interesting question of EBV’s function in the etiology of AITL. AITL most often presents late in the disease course with diffuse systemic involvement, including hepatosplenomegaly, lymphadenopathy and other symptoms such as rash with pruritis and arthritis. Lab findings include cold agglutinins, rheumatoid factor and anti-smooth muscle antibodies. There also tends to be immunodeficiency secondary to the neoplastic process. The clinical course of AITL is variable, but the prognosis is poor, with the average survival time after diagnosis being < 3 years. The histological features and genetic findings have not been found to impact clinical course.

Microscopically, AITL presents with either partial or total effacement of the normal lymph node architecture with perinodal infiltration. The cells of AITL are small to medium-sized lymphocytes with clear to pale cytoplasm, distinct cell membranes and very minimal cytological atypia. These cells often congregate around the high endothelial venules. The T-lymphocytes are present in a largely polymorphous inflammatory background of other lymphocytes, histiocytes, plasma cells and eosinophils. There are 3 overlapping sub-patterns of AITL. The first of these is similar to a reactive follicular hyperplasia, and can only be distinguished from normal hyperplasia by use of immunohistochemical stains to differentiate the neoplastic cells from normal reactive cells. The second pattern has retained follicles, but they show regressive changes. The third pattern has completely or sub totally effaced. These three patterns seem to be on a spectrum with one another, given that progression from the first to the third pattern has been seen on consecutive biopsies in the same patient.

Cytologically, AITL cells express pan-T-cell markers including CD2, CD3 and CD5 and the vast majority are CD4 positive. CD3 may be quantitatively decreased or absent by flow cytometry. There are a variable number of CD8 positive T-cells. The tumor cells also show the immunophenotyping of normal T follicular helper cells including CD10, CXCL13, ICOS, BCL6 and PD1 in 60-100% of cases. CXCL13 and CD10 are the most specific, whereas PD1 and ICOS are the most sensitive.

References

  1. Horne, C., Fraser, R., & Petrie, J. (1974). Angio-Immunoblastic Lymphadenopathy With Dysproteinemia. The Lancet, 304(7875), 291. doi:10.1016/s0140-6736(74)91455-x
  2. Harris, N.l. “A Revised European-American Classification of Lymphoid Neoplasms: a Proposal from the International Lymphoma Study Group.” Current Diagnostic Pathology, vol. 2, no. 1, 1994, pp. 58–59., doi:10.1016/s0968-6053(00)80051-4.
  3. Swerdlow, Steven H. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. International Agency for Research on Cancer, 2017.
  4. “Angioimmunoblastic T Cell Lymphoma.” Pathology Outlines – PathologyOutlines.com, http://www.pathologyoutlines.com/topic/lymphomanonBAITL.html.

-Zachary Fattal is a 4th year medical student at the Central Michigan University College of Medicine. He is pursuing a career in pathology and has a special interest in hematopathology, cytopathology and blood bank/transfusion medicine. You can follow him on Twitter @Paraparacelsus.

Kamran M. Mirza, MD, PhD, MLS(ASCP)CM is an Assistant Professor of Pathology and Medical Education at Loyola University Health System. A past top 5 honoree in ASCP’s Forty Under 40, Dr. Mirza was named to The Pathologist’s Power List of 2018. Follow him on twitter @kmirza.

Microbiology Case Study: A 64 Year Old Post-Chemotherapy Female

Case History

A 64 year old female with metastatic left breast cancer, status-post chemotherapy, presented for erythema, discomfort, and oozing from her port site for approximately one month. At presentation she was afebrile. Her port site exhibited erythema and fluctuance. Her most recent absolute neutrophil count was 1910/cmm. Her port was removed, and a tissue specimen was sent for microbiologic examination.

Laboratory Identification

Gram stain showed neutrophils without bacteria. Aerobic cultures grew a beaded gram positive rod on blood agar at 36 hours. Kinyoun stain was positive for acid fast bacilli. Matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) at that time identified Mycobacterium fortuitum group.

Image 1. Growth on 7H10 agar.
Image 2. Kinyoun stain showing acid fast bacilli.

Discussion

M. fortuitum is a group of rapid growing mycobacteria. Within the group is M. conceptionense, M. houstonense, and M. senegalense. The group comprises the second most-commonly isolated rapidly growing mycobacterial respiratory isolates in patients (after M. abscessus), generally those with underlying lung disease. Progressive pulmonary disease is generally not seen.  It has also been associated with skin and soft tissue infections (SSTIs), surgical wound infections, lymphadenitis, and catheter-related infections. It is seen in the environment and represents a common contaminant. Identification is by culture and molecular techniques. It is susceptible to many antibiotics (typically aminoglycoside, cefoxitin, imipenem, or levofloxacin). Therapy includes two agents based on susceptibility testing for 6 to 12 months. This is somewhat controversial in pulmonary disease as the clinical significance is not clear.

This patient is being treated through a peripheral IV. The chest port site at two weeks showed dehiscence of the wound with drainage. Susceptibilities are pending.

References

  1. Park S, Suh GY, Chung MP, Kim H, Kwon OJ, Lee KS, Lee NY, and Koh WJ. Clinical significance of Mycobacterium fortuitum isolated from respiratory specimens. Respiratory Medicine. March 2008;102(3):437-442.
  2. Sethi S, Arora S, Gupta V, Kumar S. Cutaneous Mycobacterium fortuitum Infection: Successfully Treated with Amikacin and Ofloxacin Combination. Indian J Dermatol. 2014;59(4):383–384.

-Jonathan Wilcock, MD 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.

Global Health Narratives Interview Series: Meet Dr. Adebowale Adeniran

Adebowale Adeniran, MD is a surgical pathologist and cytopathologist currently practicing at Yale University and serves as the Director of Cytopathology there. He completed his medical school training in Nigeria and moved to the United States to complete a residency and fellowship.

I am fortunate enough to know him as my future attending, as I will be joining the cytopathology fellowship program at Yale in 2020. I also know him through attending last year’s Friends of Africa meeting at USCAP, where he gave a presentation about the status of pathology services in Africa. His points were compelling and he spoke with passion and heart about the issue. He is a true global health advocate and I was delighted to have the chance to talk with him about the work that he is doing in Africa and learn more about the USCAP Friends of Africa group. Read on to be inspired by his commitment to global health and learn how you can also get involved!

Q: How did you recognize the need to contribute to improving pathology services in Africa?

A: Being from Nigeria and having worked there for a short time as a House Officer, I knew that there were improvements to be made in the healthcare delivery system, but I hadn’t thought of improving pathology services specifically. It wasn’t until I was in my second fellowship at Memorial Sloan Kettering that I had the opportunity to meet Dr. Brian West. He told me about the USCAP Friends of Africa group in which he was an active part and had been since the start. He was involved in education initiatives and would routinely travel to Africa to give lectures and educational seminars.

I went to the next Friends of Africa meeting at the annual USCAP meeting and was able to speak to others doing similar work to Dr. West. This inspired me to also get involved and have been participating in the group ever since. I learned that pathologists practicing back home in Nigeria, and in most other countries in Sub Saharan Africa, face challenges in practicing pathology that we don’t have in the US. It only takes seeing the situation once to realize the great need there is. There are a range of problems, from outdated equipment, to supply shortages, to all of the things that we take for granted like consistent access to electricity and water supply. In general, governments tend to be apathetic to funding healthcare and especially pathology services, which results in compromised patient care with very few pathologists to read cases, long turnaround times, and limited diagnoses. The training programs are usually working with few or old textbooks and limited exposure to advanced testing modalities. You see these problems and your heart bleeds; you feel compelled to get involved and give back.

Q: What is the mission of the USCAP Friends of Africa?

A: The organization has evolved and expanded over the years to increase their outreach to Sub Saharan Africa with the aim of improving pathology services there. The main leaders in the group, Drs. Adekunle Adesina, Patrick Adegboyega, Kunle Adesokan, and Jaiye Ogunniyi-Thomas have made big strides since the start and pathology has come a long way because of it. The group is supported by the USCAP Foundation and they work to distribute free educational materials to pathologists and training programs. They also work with the East and West African divisions of the IAP in developing and hosting teaching projects called “Schools of Pathology”, which are special yearly meetings. They are usually around a weeklong of intensive teaching and mentoring, and they will be held in different countries in West and East Africa to equalize the opportunities for people to participate. Pathologists from across the regions travel to be a part of it.

Q: What ways have you found to contribute to improving pathology services in Africa?

A: For the last five or six years, I’ve worked most frequently in Nigeria in my medical school alma mater, where I travel back yearly to give lectures and teach residents with slide sessions. It’s also a good opportunity for me to review any difficult cases with the department and offer an outside consultation. I also send journals and reading materials they don’t have access to otherwise. I’ve also had opportunity to work with three other medical schools in the area in similar ways.

Volunteering with USCAP Friends of Africa, I participated in last year’s School of Pathology meeting that was held in Lagos, Nigeria. This was the first time that I was able to teach in that program and it was a very good experience.

Q: In what ways can the pathology community get involved with global health?

A: One very simple and easy way to contribute is to give a donation to the USCAP Foundation Global Partners. Every year since 2015, they sponsor pathologists from low and middle income countries to travel to the USCAP meeting through a scholarship, the Global Partners Travel Award. This supports those who often don’t have easy access to attending academic conferences and who cannot afford the travel cost and meeting registration fees to travel to USCAP.

Another is by attending the USCAP Friends of Africa meeting at the annual USCAP meeting and signing up for the many ways you can volunteer your time and expertise. Anyone who has the desire and ability to go and teach, organize slide sessions, or collaborate on research projects, has the opportunity to do so through this organization. These things go a long way and are really appreciated.

Donations of textbooks, supplies, and equipment such as cryostats are also needed. Developing the laboratory services in these countries is really needed and I would encourage those who can to set up private pathology laboratories to help meet the need.

Academic institutions in the US can offer ways of enhancing training opportunities for African pathologists and trainees by offering short- or long-term exchange programs. This helps to bridge the gap between practiced based learning in resource limited vs. US institutions.

-Dana Razzano, MD is a Chief Resident in her third year in anatomic and clinical pathology at New York Medical College at Westchester Medical Center and will be starting her fellowship in Cytopathology at Yale University in 2020. She was a top 5 honoree in ASCP’s Forty Under 40 2018 and was named to The Pathologist’s Power List of 2018. Follow Dr. Razzano on twitter @Dr_DR_Cells.

A Pathology Emergency

Hi everybody! Welcome back. Thanks for following along last month’s update on Zika epidemiology and clinical lab crossovers. This time I’ve got a story to tell…

This is my last month of medical school! And, as such, I decided to go out with a bang and finish up with my last rotation in Emergency Medicine at The Brooklyn Hospital Center. It was a fantastic month! One would think that EM and Path are two very distant specialties, but they are more alike than you might realize. That could be a whole separate article but consider this: managing critical situations, ensuring fast-paced accurate response times, engaging in high-stakes algorithms, and making sure mistakes are caught early. Sounds to me like there’s lots of overlap…remember my discussion on high reliability organizations or the critical role interdisciplinary medicine plays in creating good patient outcomes? All things aside, all clinicians have a critical role to play, but what happens when you put an (almost) pathologist in an emergency room?

Basically, you get me having a fun four weeks—I used to be an EMT and help teach EMS courses, so I do like this stuff. But something else happened this month that really made this experience special…

Image 1. Typically, med students have minor roles to play in real-life critical codes, but some of our duties include managing monitor attachments for vital signs, securing peripheral IV access, obtaining emergency labs, and other supportive measures while the rest of the code team manages…well, the resuscitation efforts. Source: Life in the Fast Lane.

Saturday, July 27th. I got to sleep in because I was on the night shift for four days. No big deal. When I finally got to the hospital, there was pandemonium. Extra ambulances in the loading bay, a couple squad cars outside, a stab wound victim in the trauma bay, lots of noise and folks everywhere—what was routine hospital stuff somehow seemed like I was in the middle of filming an actual episode of ER. (I’m obviously partial to particular shows…okay, maybe Chicago Med?) When I report to my team, I learn that the computers have been down. All day. No electronic health records, no charting, no histories, no internet to look up guidelines/recommendations on UpToDate—and most tragically: no lab results.

Ok. This is it. I’m on the other (read: clinical) side of an awful downtime shift. I’ve experienced plenty of downtime in the lab, but this night I took a deep breath, reminded myself its going to be okay, and did my best to label things right. But a problem appears that’s more serious than labeling type and screens the right way without a computer: results are backlogged for hours! I’m talking no blood gases, no lactic acids, no pregnancy confirmations! I overheard senior residents and my attending that night talk about how the lab is struggling and they didn’t have enough people to figure out this downtime debacle.

This was a moment. It’s not often med students get to be literally useful in any clinical situation but after high-speed thinking about it, I interjected and made my elevator pitch:

“Dr. X, Dr. Y – I’ve got several years of hospital lab experience and lots of background in managing crises and downtime situations, if you want I’ll head over to the lab and see if I can help this situation at all, at least for the ER…”

There was a short pause. Then an enthusiastic wave of approval with hands waving me to go help out our laboratorian colleagues. Please note: the instances where tidbits of knowledge as a medical laboratory scientist prove useful as a medical student on rounds are far and few between for their ability to really captivate a group of doctors who identify themselves far from any lab medicine; so, this was a win. Explaining the importance of order of draw, or why sensitivity goes down when you don’t adequately fill blood cultures, or why peripheral smears should come with some interdisciplinary caveats aren’t quite as sexy as an emergency room, on metaphorical fire, with no one but you knowing anything about how labs work.

So, I ran on over to the laboratory, fully intending to do what I could to help in my unofficial just-a-friendly-neighborhood-med student capacity. That’s when I met Jalissa Hall!

I walked into the main lab area and asked if I could talk to the supervisor, thinking I would just explain my experience and offer what I could to their staff who I’m sure were buried in downtime SOPs and make sure I got critical results back to my team in the ER—a win-win! When I asked who was in charge, a very busy Ms. Hall walked out from behind the chemistry section and said, “you can talk to me. What’s going on?” I’m sure she thought I was there to complain, seemingly like many other clinicians were, but I stopped and gave her the same elevator speech I delivered moments ago with the postscript: “what can I do for you?” I remember she stopped, thought about if for roughly 10 seconds, and presented me with her situation briefing:

  • Computers have been down since roughly 05:00 am
  • There’s a computer virus that had all servers shut down indefinitely
  • There’s no communication between the hospitals EHR and the labs LIS
  • Moreover, no patient information is coming across to the analyzers (MRNs, specimen IDs, etc.)
  • There are 4-5 critical units (ER, OR, ICU, OB, NICU) that require STAT results
  • Clinicians have been coming to the lab all day looking for informal results reporting
  • The limited lab staff has had to manually print results on paper and work to match them with barcodes, specimens, and manual requisitions before releasing results
Image 2. Jalissa Hall, MLS(ASCP) (left) and a very tired me (right) after a great night of solving lab-related communication problems! Anyone else need an emergency room pathologist? Sounds like a new clinical specialty/fellowship to me…

Deal. I know I can’t jump on the analyzers because New York is one of the states that requires clinical laboratory licensure (which I do not hold). In my informal survey I noted three medical lab scientists (including Ms. Hall), someone in specimen processing, and someone in blood bank. Basically, in order to make sure the lab could operate at peak performance with what they had, I helped alleviate the “paper problem” for them at least for the ER specimens. I matched requisitions with instrument raw data, made copies for downtime recording, delivered copied results to the ER, rinsed, lathered, and repeated—for eight hours! I obviously had to toe the line for the ER results, but there were other nurses and doctors who came in for the other areas’ results. No one worked more than the folks in that lab that night, and no one more so than Jalissa. After things cooled down a bit, I got the chance to connect with her and talk about her career and asked if she had anything to share with all of you—she definitely did.

Lablogatory family: please meet Jalissa Hall, MLS (ASCP)!
(Responses paraphrased because, honestly it was late, and downtime was busy, and we were tired, ok?)

Jalissa has been working for about five years as a generalist, with two jobs—like most of us have done. She works at The Brooklyn Hospital Center as a generalist and at NYU Hospital Lab in their hematology section. She is a graduate from the excellent MLS program at Stony Brook University in NY. She’s got ambitious career goals that are aimed at climbing as high as she can in laboratory medicine, and she’s got the enthusiasm and work ethic to match! I got the chance to ask her some real questions, during a real down-time crisis. This is what she had to say:

What made you go into laboratory medicine?

JH: I really want to help people. I love the behind-the-scenes aspect of being a medical laboratory scientist, but I think sometimes it can be too behind the scenes…

What did you think of tonight’s downtime issues?

JH: …it could have gone better. There seems to have been some panic, people kept walking in and shuffling the papers around. I tried my best to organize by floor, have two copies of each result (one for us and one to send upstairs), and requisitions match orders, but it was difficult. We have a downtime protocol, but we just couldn’t keep up with the volume and extent of how long it’s been down for. There’s really been no help outside the lab to work with us during this time so it’s a challenge.

What could have happened better?

JH: No outside help meant no room to breathe. On the inside, supervisors off duty tonight called staff in but none were available to come in. We don’t have an on-call person. We’re understaffed or short-staffed like so many labs out there; it’s problematic.

How is this going to look tomorrow?

JH: It’s not looking good, haha! Morning draw is definitely going to have a hard time. Catching up with these backlogs is one thing, but if orders can’t come across the LIS we’ll have to address that problem for sure. We’ve got a great staff though, so I’m sure it’s going to be fine.

What would be your “top tips” for all our fellow laboratorians reading this?

JH: First and foremost, being driven matters. If you want to get ahead, if you want to excel and climb high within an organization or in our profession, you have to work hard and keep working toward your goals.

Pro-tip #1: One of the biggest issues is “vertical cooperation.” Basically, some call it administration-buy-in, but it means administration working with employees in the lab to make the best decisions for our patients. If employees are burned out or if there aren’t enough resources to effectively perform our responsibilities it creates risks! It all comes down to patients, and making sure we’re in the best position to deliver diagnostic data for them means considering all aspects of lab management.

Pro-tip#2: If we want to fix the workforce shortages our labs regularly experience, we have to increase our efforts in advocacy within our profession. Having programs increase awareness of this job as a profession increases the pull and interest of potential new partners to work with. My school did it, other schools do this; increasing the number of programs that expose students to career opportunities in lab medicine would address our short-staffing problems everywhere!

Pro-tip #3: TELL OTHERS ABOUT OUR PROFESSION! I talked about our role being too behind the scenes…well the way to fix that is professional PRIDE! Own our accomplishments, share our role, advocate for our recognition, celebrate our peers!

Pro-tip #4: The future is not scary. Lots of folks shy away from tech advancement, fearing that automation and other developments mean losing jobs—it doesn’t. Why can’t today’s lab scientists become tomorrows experts on automation, LIS software, and other aspects of our cutting-edge field?

It was a pleasure to meet Jalissa and even better to work alongside her and learn about her passions and goals within the field we both care about! It was particularly special for me to be able to use my knowledge and experience to really contribute to my clinical team and bring laboratory medicine to the forefront where it doesn’t often shine!

Image 3. In a fantastic book I read recently, the authors of You’re It: Crisis, Change, and How to Lead When it Matters Most talk about leadership as a moment—a moment where you step up to a situation because you have skills and experiences which make you uniquely qualified to serve in a role which aims at a positive outcome. I had a small version of that in front of my attending (important for evaluations in medical school of course), but that downtime night was Jalissa’s “you’re it” moment for sure! (Source: Google)

Signing off from any new clinical rotations because this guy’s done with his medical school clerkships! Now I’ve gotta knock out some board exams and go on some residency interviews…wish me luck! I’ll check in with you next month after the 2019 ASCP Annual Meeting in Phoenix, Arizona—hope to see some of you there!

See you all next time and thanks for reading!

–Constantine E. Kanakis MSc, MLS (ASCP)CM graduated from Loyola University Chicago with a BS in Molecular Biology and Bioethics and then Rush University with an MS in Medical Laboratory Science. He is currently a medical student actively involved in public health and laboratory medicine, conducting clinicals at Bronx-Care Hospital Center in New York City.

Microbiology Case Study: An 18 Year Old with Fever, Chills and Abdominal Pain

Clinical History

An 18 year old male presented to the emergency department (ED) with fever, chills, and generalized lower abdominal pain. He noted the fever began 6 days ago and had been intermittent since that time. He also reported nausea and vomiting with a decrease in appetite. The patient was from India and was treated for malaria 8 months ago, directly prior to arrival in the United States. He stated he received three days of intravenous medications with resolution of symptoms. In the ED, his vitals were blood pressure 129/75, heart rate 133, temperature 104.1°F, respirations 20, and 99% oxygen saturation on room air. On physical exam, patient had mild jaundice and scleral icterus and severe right lower quadrant pain on palpation. CT scan of the abdomen showed mesenteric adenitis, but no appendicitis. Initial laboratory testing showed a mild anemia and thrombocytopenia (hemoglobin 12.1 g/dL, hematocrit 35.9%, platelets 78,000 TH/cm2) and increased indirect bilirubin (2.67 mg/dL). The patient received piperacillin-tazobactam while blood and urine cultures as well as a malaria smear were pending.  

Laboratory Identification

The BinaxNOW lateral flow immunochromatographic assay for Plasmodium spp. was performed.

Image 1. The BinaxNOW assay was positive for malaria protein antigen, representing P. vivax, P. ovale, P. malariae, or a mix of these species.
Image 2. A thin smear showed amoeboid gametocytes in enlarged red blood cells as compared to uninfected cells (Giemsa stain, 100x oil immersion).
Image 3. A thin smear showed very rare trophozoites with thick chromatin bands and single, large chromatin dots (Giemsa stain, 100x oil immersion).

The positive BinaxNOW results and morphologic findings on smear review were most consistent with a P. vivax infection. The level of parasitemia was approximately 0.2%. Blood and urine cultures were negative.

Discussion

Malaria classically presents with fever and chills, weakness, headache, myalgias, nausea, and vomiting in patients who live in tropical and subtropical regions. The four most common species that infect humans through transmission by the female Anopheles mosquito include P. falciparum, P. vivax, P. ovale, and P. malariae. If malaria is not diagnosed and treated in a timely manner, complications including anemia, thrombocytopenia, renal failure, acute respiratory distress syndrome (ARDS), and cerebral malaria can result. P. falciparum is the most deadly species due to the parasite’s ability to cause high levels of parasitemia.  

In laboratories in the United States, malaria testing often times incorporates Plasmodium spp. antigen detection via the BinaxNOW assay and peripheral blood smears. While the performance of the BinaxNOW is acceptable, particularly for P. falciparum, thick and thin peripheral blood smears remain the gold standard for malaria diagnosis, especially when the parasitemia level is low. The thick blood smear allows for screening a large amount of blood for malarial parasites and the thin smear allows for species identification and assessment of parasitemia. Ideally, multiple blood smears obtained from different times of the day should be collected in order to exclude the diagnosis. The window prior to a febrile spike is the best time to obtain the specimen, as the number of circulating parasites is greatest.

Clinically, the most important distinction is between P. falciparum and all other species. A number of features including the morphology of the trophozoites, schizonts, and gametocytes, size of the infected red cells, the presence of multiply infected red blood cells, and the region that the patient lives in or traveled to are helpful in determining species level identification.

P. vivax infects enlarged, young red blood cells and multiple trophozoites may be present in one red blood cell. The trophozoites have thick, blue cytoplasm and usually one, large chromatin dot. The schizont can contain 12 to 24 merozoites and the gametocyte is large and oval in shape. Schuffner’s stippling and malarial pigment are common. It is important to correctly identify P. vivax and P. ovale as they have hypnozoite forms in the liver and patients can relapse unless they are treated with an additional medication to eradicate these forms.

In the case of our patient, he received chloroquine, the treatment of choice for P. vivax arising in India. Primaquine and tafenoquine are both options for eradication of the hypnozoite form in the liver. These medications can cause hemolytic anemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency so quantification of the enzyme is required prior to administering therapy. Our patient had normal G6PD levels and received tafenoquine as well. 

-Karla Perrizo, MD, is a clinical pathology resident at the University of Mississippi Medical Center.

-Lisa Stempak, MD, is an Assistant Professor of Pathology at the University of Mississippi Medical Center in Jackson, MS. She is certified by the American Board of Pathology in Anatomic and Clinical Pathology as well as Medical Microbiology. She is the Director of Clinical Pathology as well as the Microbiology and Serology Laboratories. Her interests include infectious disease histology, process and quality improvement, and resident education.