Friday School 5/20/2022

Today’s FriYAY School is all about hematology: hemochromatosis and coagulopathy.

Here to shed some light on hemochromatosis, particularly hereditary hemochromatosis (HH), is Dr. Heather Patton, the Gastroenterology Section Chief at VA San Diego. Most cases of HH are caused by mutations in the HFE gene; most patients (80-85%) have a C282Y/C282Y genotype, and about 5% have a C282Y/H63D genotype. Disease manifestations usually occur earlier in men than in women and can include hepatic dysfunction (including cirrhosis and hepatocellular carcinoma), endocrinopathies (classically diabetes), cardiomyopathy, arthropathy, and skin hyperpigmentation. This diagnosis is suggested by a transferrin saturation >45% and serum ferritin >200-300. Hepatic iron excess can be demonstrated with a liver biopsy or liver MRI. Genetic testing can help confirm the diagnosis. Treatment is with therapeutic phlebotomy and chelation.

Our residents were then joined by Dr. Jenny Zhou, one of our awesome hematologists, who walked our residents through a case-based discussion of coagulopathy. After a brief review of primary and secondary hemostasis, we looked at how we can use different coagulation studies to identify the cause of a patient’s coagulopathy.

What a great overview of these two challenging topics! Thank you, Drs. Patton and Zhou!

VA MTC 5/19: Double Flu!

Today for MTC, one of our awesome second year residents, Jessica Hansen, presented a fascinating case of a patient who presented with 1 week of shortness of breath. His past medical history included COPD, heart failure, and a recent surgery making his initial differential diagnosis very broad: COPD exacerbation, volume overload, PE, and pneumonia.

The patient was febrile and hypoxemic on presentation, and his chest x-ray revealed bilateral, right > left, heterogenous opacities. We took the opportunity to review the approach to reading chest x-rays for the brand new MS3s!

The patient’s initial work-up revealed he was positive for both Influenza A and Haemophilus influenza! Double Flu! With help from our expert discussant and ID fellow, Mike Doud, we discussed indications for the treatment of viral influenza.

  • Influenza antiviral treatment is recommended as early as possible for any patient with confirmed or suspected influence who:
    • is hospitalized
    • has severe, complicated, or progressive illness, or
    • is at higher risk for influenza complications (Age > 65, asthma, chronic lung disease, heart disease, kidney disease, liver disease, BMI > 40…)
  • Antiviral treatment also can be considered for any previously healthy, symptomatic outpatient not at high risk for influenza complications, who is diagnosed with confirmed or suspected influenza, if treatment can be initiated within 48 hours of illness

Thank you so much to Mike Doud for joining us today and to Jessica Hansen for sharing this awesome case!

Jacobs Conference 5/18/2022: EBM

The focus of our Jacobs afternoon conference is… evidence-based medicine! Yay!

Starting us off, Dr. Helen Chou, second-year resident and future hospitalist, reviewed four studies that examined the utility of echocardiography in patients who present with syncope. She concluded that in patients whose history, physical exam, and ECG do not suggest a cardiac cause, the diagnostic yield of echocardiogram was extremely low (0-1%). Echocardiogram may be more helpful in patients with a history of cardiac disease, exam findings suggestive of structural heart disease, or abnormal ECG. The San Francisco Syncope Rule may also help risk-stratify these patients.

We then looked at whether octreotide improved symptoms such as pain, nausea, and vomiting in patients with malignant bowel obstruction. We dissected three randomized controlled trials that compared octreotide to scopolamine or placebo. There is low-quality evidence that octreotide may reduce nausea, vomiting, and pain, although higher-quality evidence has yet to confirm this benefit. Because of the cost of octreotide, decision to use it should be made on a case-by-case basis with the support of a multidisciplinary team.

Grand Rounds 5/18: Inflammatory Bowel Disease with Dr. John Chang

Today for our DOM Grand Rounds, Dr. John Chang presented on his incredible research on the immune mechanisms that underly lymphocyte fate specification. Dr. Change is a gastroenterologist, physician-scientist, and the principle investigator for the Chang Laboratory at UCSD.

Dr. Chang discussed his journey to becoming a physician-scientist, reviewed some of the work he has already accomplished, and highlighted his visions for future research in this field.

You can check out one of his review articles in the NEJM here:

Thank you so much, Dr. Chang, for sharing your work with us today!

Noon Conference 5/17/2022: MPNs

Myeloproliferative neoplasms (MPNs) are a group of clonal hematopoietic stem cell disorders that are quite distinct from myelodysplastic syndromes. Here to shed light on these diagnoses is hematologist and oncologist Dr. Michael Choi.

Chronic myeloid leukemia (CML) is characterized by the presence of the Philadelphia chromosome, t(9;22), which results in BCR-ABL1 fusion. It can be divided into the chronic phase (<10% blasts), accelerated phase (10-29%), and blast phase (30%+). Treatment is with tyrosine kinase inhibitors (TKIs)— imatinib (the OG TKI), dasatinib, nilotinib, or ponatinib—which inhibit BCR-ABL1 fusion protein function. Allogeneic hematopoietic stem cell transplantation is an option for patients with accelerated- or blast-phase disease.

Polycythemia vera (PV) presents as increased RBC mass and is classically associated with the JAK2 V617F mutation. Therapeutic phlebotomy is used to target a hematocrit goal of <45%, and iron supplementation is avoided even when deficient. Essential thrombocythemia (ET) presents as thrombocytosis and thrombosis; it is also associated with JAK2 mutations, though mutations in calreticulin (CALR) and thrombopoietin receptor (MPL) can also lead to ET. Low-dose aspirin is given to patients with PV and ET to lower the thrombotic risk. Depending on patient’s risk, cytoreductive therapy with agents such as hydroxyurea and ruxolitinib may also be indicated for treatment of PV and ET.

Hypereosinophilic syndrome (HES) is diagnosed when a patient presents with a sustained eosinophilia >1500/μL and evidence of resultant end-organ damage. Most cases result from mutations in platelet-derived growth factor receptors.

Primary myelofibrosis (PMF) generally has the worst prognosis among all MPNs. Patients have bone marrow fibrosis, ectopic hematopoiesis, and massive splenomegaly. Treatment options are limited and often involves allogeneic stem cell transplantation.

Thank you, Dr. Choi, for this very high-yield discussion of MPNs! Great job, Dr. Janna Raphelson, one of our RACE Track residents, for helping create the session!

VA MTC 5/17/22: Enterococcal bacteremia

This morning we discussed a patient who was recently admitted to the VA with enterococcal bacteremia. We reviewed the workup and treatment of enterococcal bacteremia. Key points to remember include:

  • Enterococcus faecium is more likely to be resistant to ampicillin, while Enterococcus faecalis is more likely to be resistant to Vancomycin.
    • However, remember that VRE faecalis may still be susceptible to Ampicillin! In fact, Ampicillin is the preferred treatment in the absence of resistance or allergy.
  • In the absence of endocarditis, critical illness or resistance, Enterococcus bacteremia may be treated with monotherapy with Ampicillin (or Penicillin, Vancomycin, Daptomycin, or Linezolid).
  • Combination therapy is indicated in cases of suspected endocarditis or critical illness. Common regimens include:
    • Ampicillin + Ceftriaxone
    • Ampicillin + Gentamicin
    • Vancomycin + Gentamicin

However, this patient expressed that several interventions, including PIV placement and the use of IV antibiotics, were not within his goals of care. He was amenable to PO antibiotics, though. We were lucky to be joined by Dr. Looney, an expert ID physician who consulted on this case, as well as Dr. Pardee, an experienced hospitalist. They gave their valuable insight into how we can individualize care in a respectful and informed way when patients decline our treatment recommendations. Thanks for the interesting discussion!

VA MTC 5/16/22: Stones Galore!

Today’s VA morning report was all about nephrolithiasis! We discussed a case of a young woman with recurrent nephrolithiasis, whose stones were a combination of calcium phosphate and calcium oxalate. Our residents worked together to compile the chart above with the crystal shapes, risk factors, underlying conditions and lab findings associated with the most common types of kidney stones. Dr. Beben, our expert nephrologist, also gave his valuable insight.

When seeing recurrent nephrolithiasis in the clinic, on the wards, or on the boards, it is important to remember:

  • Pay attention to the urine pH! This can be a helpful clue to the type of stone.
  • 24-hour urine collection, collected at least 1 month after an acute episode of nephrolithiasis, UTI, or urologic procedure, can also help to identify underlying problems such as hypercalciuria, hypocitraturia, hyperoxaluria, hyperuricosuria, and cystinuria.
  • Citrate is an important inhibitor of calcium crystallization in the urine. Therefore hypocitraturia can predispose patients to calcium stone formation.
  • Increasing fluid intake to a goal OUP of >2.5 L is an important recommendation regardless of the type of stone!
  • Other useful dietary changes, depending on the type of stone, include:
    • Low dietary sodium (Remember: calcium follows sodium and water!)
    • Low oxalate diet
    • Limit animal protein
  • *Limiting dietary calcium is NOT recommended
  • Some of the most common pharmacologic interventions may include:
    • Potassium citrate or potassium bicarbonate (helps with most types of stones by various mechanisms)
    • Thiazide diuretics (helps with calcium stones by decreasing urinary calcium)
    • Allopurinol (for uric acid stones)

Hillcrest MTC 5/16: CMV, EBV, and False Positive HIV

Today for morning conference, we discussed a very interesting case of a young man who presented with generalized malaise, abdominal pain, and fevers. We were joined by one of our amazing Owen attendings, Dr. Laura Bamford, who helped us work through this case. The patient was found to have hepatosplenomegaly on exam and initial work-up revealed positive CMV IgM, EBV IgM, and rapid HIV test. We did a quick review of CMV and EBV infection in immunocompetent people and discussed the HIV testing algorithm.

  • EBV
    • Aka HHV 4
    • Transmission: Primarily through saliva
    • Presentation: Fever, severe fatigue, exudative pharyngitis, cervical and axillary LAD, and splenomegaly
    • Highly prevalent with almost all adults having serological evidence of prior infection
    • Diagnosis: Typically a clinical diagnosis based on presentation and exposure risks. Atypical lymphocytosis, elevated transaminases and EBV IgM to viral capsid antigen can also help with diagnosis.
      • Monospot to heterophile antibodies is cheap and quick, but it isn’t routinely recommended by the CDC because the antibodies detected can be caused by conditions other than EBV infection
  • CMV
    • Aka HHV 5
    • Transmission: Saliva, blood, transplant, placenta, and breastfeeding
    • Presentation: Most healthy, immunocompetent people have no symptoms, but it otherwise can have a very broad range of clinical manifestations including colitis.
    • 60-90% of adults have latent CMV infections
    • Diagnosis: Serological assays have limited utility because most adults are seropositive. Diagnosis can be confirmed with molecular tests, biopsy revealing classic “owl’s-eye” intracellular inclusions, or by CMV immunostaining.

The patient improved with supportive treatment and was thought to have a false positive rapid HIV test. Thank you so much to Dr. Bamford for joining us today!

Friday School 5/13/2022

During today’s Friday School, our residents were treated to some great interactive sessions on breast cancer, colorectal cancer, and transfusion reactions.

Dr. Rebecca Shatsky, an amazing breast oncologist, taught us about breast cancer, which affects 1 in 8 women. Risk factors include age, genetics, low parity, estrogen exposure, dense breast tissue, radiation, obesity, and alcohol. Symptoms may include lumps in the breast, changes in the breast or skin overlying the breast (including peau d’orange), and discharge or bleeding from the nipple. For the general population, it is reasonable to start annual mammography at age 40, though guidelines differ. Treatment of breast cancer is determined by stage, grade, ER and HER2/neu status (most commonly ER+/HER2), and sometimes molecular typing (e.g., Oncotype DX). We reviewed surgical treatment and common chemotherapy agents used to treat breast cancer—tamoxifen, aromatase inhibitors (e.g., anastrozole), anthracyclines (e.g., doxorubicin), anti-HER2 monoclonal antibodies (e.g., trastuzumab), CDK4/6 inhibitors (e.g., abemaciclib), and PARP inhibitors (e.g., olaparib)—including their indications and important toxicities to consider.

Switching gears, Dr. Greg Botta came to our Friday School to discuss the care of patients with colorectal cancer. Patients are often diagnosed on screening or after presenting with changes in bowel habits, pain or discomfort during bowel movements, bleeding, or anemia. Some patients may have a family history of colorectal cancer (e.g., familial adenomatous polyposis, Lynch syndrome). The stage, grade, location, microsatellite status, and molecular profile of the tumor (e.g., mismatch repair genes) inform management. Patients with nonmetastatic disease will generally undergo surgery; most patients with metastatic disease do not benefit from surgery. Observation is reasonable for stage I-II disease, curative chemotherapy is appropriate for stage II-III and now some stage IV disease, while palliative chemotherapy is an option for the remaining stage IV disease. Important chemotherapy agents to remember include 5-fluorouracil (5-FU), capecitabine, oxaliplatin, irinotecan, bevacizumab, and immune checkpoint inhibitors. Dr. Botta also briefly discussed how circulating tumor DNA (ctDNA) allowed us to management patients with colorectal cancer in a more nuanced manner.

During the last two hours, Dr. Elizabeth Allen, one of our blood bank faculty members, led our interns and residents through a whirlwind tour of transfusion reactions, including acute hemolytic transfusion reaction, acute febrile non-hemolytic transfusion reaction, transfusion-related acute lung injury (TRALI), urticarial and anaphylactic transfusion reactions, transfusion-associated circulatory overload (TACO), delayed hemolytic transfusion reaction, and transfusion-associated graft-versus-host disease (TA-GVHD). We then went through a number of practice cases that illustrated how to recognize, diagnose, and manage patients who experience each of these transfusion reactions.

Thank you to all of our speakers for a very educational Friday School session!