All posts by gsmith003

ZSFG AM Report Pearls 3/28/2018: B-b-b-b-b-bad, Bad to the Bone Marrow: ET, PV, and MDS Mutations and Work-Up

On this day, we discussed an elderly patient who presented with leukocytosis and severely elevated platelets. We discussed the DDx for these findings as well as some of the common genetic tests. Shout out to Corynn Kasap for dropping some serious knowledge on all of us!


See the NEJM article referenced in the sources for more information, but this is super interesting!

Myeloproliferative Neoplasms:

These are three hematopoietic stem-cell disorders that share mutations that activate the physiologic signal-transduction pathways responsible for hematopoiesis.

  • Polycythemia vera
  • Essential thrombocytosis
  • Primary myelofibrosis

The mutations that are most commonly involved in these diseases include:

  • JAK2
  • MPL
  • CALR
  • Cases are often from sporadic mutation, but about 7% of cases involve familial predisposition
  • Pathogenic mutations have been identified in more than 90% of patient with myeloproliferative neoplasms
    • 50-60% of patient have only a driver mutation: JAK2, CALR, MPL or in rare cases LNK
    • These mutations are not mutually exclusive, nor are they exclusive to a particular myeloproliferative neoplasm and their absence does not preclude any of these neoplasms!
  • These myeloproliferative neoplasms can evolve into others and can develop into AML
  • Spivak JL. (2017). Myeloproliferative neoplasms. NEJM. 376:2168-2181.




ZSFG AM Report Pearls 3/27/18: 2 Steps Forward, 2 Steps Back: Paradoxical Reactions & IRIS in TB Tx in HIV+ Pts

Hey Team! Playing a little catch up on these awesome pearls from late March. We discussed an interesting case of an HIV+ pt who was diagnosed with TB. After starting TB tx, they ended up looking more sick and had to pause treatment. This brought up discussion about paradoxical reactions in treating TB as well as a few other pearls:
Epidemiology of TB in the US:
In the US, only 3.2% of the population is estimated to have latent TB
There are only 11,000 cases annually of active TB (remember though what your base population is – San Francisco, CA is not Dayton, OH)
>50% of cases are are in individuals born outside of the US
In the US, only 10% of cases in the US are coinfected with HIV
Extrapulmonary TB:
Prevalence = 10-42% worldwide depending on the race or ethnic background, age, presence/absence of underlying disease, genotype of the M. tuberculosis strain, and immune status (note that this is probably lower given US population)
Can affect any part of the body with a wide range of clinical presentations
TB Treatment and Paradoxical Reactions:
Paradoxical reactions to TB treatment – defined as the worsening of existing lesions or presentation of new lesions during anti-TB therapy nad typically associated with exaggerated inflammatory symptoms like fever, lymphadenitis and pulmonary manifestations
Epidemiology: Frequency somewhere between 2% and 23%
  • HIV infection is also associated with a syndrome in which paradoxical inflammatory consequences occur during therapy: the immune reconstitution inflammatory syndrome (IRIS).
    • Here, the commencement of HAART leads to an exacerbation of an existing opportunistic disease, or unmasking of a previously subclinical infection.
  • IRIS is most frequently observed in mycobacterial infections
    • Several forms have been described in HIV/TB co-infected individuals
      • The commonest of these is paradoxical TB-IRIS, in which inflammatory exacerbations of TB symptoms occur after commencement of HAART in HIV-seropositive patients being treated for active TB,15 the frequency of which was estimated to be 15.7% in a meta-analysis of 3459 individuals.
      • A second form, unmasking TB-IRIS, is when a new presentation of active TB arises after commencing HAART. The occurrence of unmasking TB-IRIS is thought to be lower than paradoxical TB-IRIS, with estimates varying between 1.4% and 23%.14,17–19 I
      • It is also suggested that HIV-seropositive individuals with active TB may have an increased incidence of PR when commencing antimycobacterial therapy, compared to HIV-seronegative individuals.
Diagnostic criteria do not yet have consensus guidelines but include worsening of clinical or radiologic findings after the initiation of appropriate antimycobaterial therapy.
The physiology behind this is not well understood and the hypotheses are based on clinical observations but are somewhat summarized in the graphic below:
  • Prior to treatment, there is a building mycobacterial load/infection, while the inflammatory system is calmed down (and likely suppressed from HIV)
  • Once you start treatment (typically for both TB and HAART for HIV) the immune system ramps up
  • In people who don’t get paradoxical reactions and IRIS, the immune system and mycobacterial load is more in sync


  • Gordin FM & Masur H. (2012). Current approaches to Tuberculosis in the United State. JAMA. 308(3):283-289.
  • Zumla A et al. (2013). Tuberculosis. NEJM. 368:745-755.
  • Bell LCK et al. (2014). Paradoxical reactions and immune reconstitution inflammatory syndrome in tuberculosis. International Journal of Infectious Disease. 32:39-45.

ZSFG AM Report Pearls 3/14/18: Just Stop Pressuring, Stop Pressuring Me, Make Me Want to Scream: Guidelines for Secondary Hypertension Work Ups

Thank you to our Cardiology team who presented this great case which was recently presented as again about a very young man who presented with severely elevated HTN, end-organ damage, and AKI on CKD who was admitted for HTN emergency and found to have ESRD requiring dialysis. This brought up a great questions about secondary HTN work-ups


2010 AAFP Guidelines:

When to Suspect:
-Resistant – doesn’t respond to BP meds
-“Very high” BP
-Age <30, or >55 years
-Sudden onset
-No family hx
-Not obese
Common Causes:
Renal: PCKD, DM nephrotpathy, HTN nephrosclerosis, GM disease, renovascular, CKD of any kind
Vascular: Fibro musc dysplasia (younger women), RAS (any age), coarctation of the aorta (teens)
Endocrine: Cushing, Pheo, Hyderaldo, Hyper-TSH, Hyper-PTH, acromegaly
Meds/Supplements: NSAIDs, cocaine, OCPs, steroids, pseudophed. SSRI, Buspar, Lithium, TCA
Other: OSA, pregnancy, obesity, scleroderma, NF1, White coat, post-surgical
-Med rec
-Age based:
     -Basic: U/A, Cr, TSH, Lytes, plasma adlo:renin, Doppler U/S, Cortisol if Cushinoid
     -19-39: TSH, FMD, renal parenchymal disease
     -40-64: Aldo, thyrdoid, OSA, cushin, pheo
     ->65: Atherosc RAS, CKD, hypo -TSH
Evaluation Based on Age:
     -MRI with gad or CT renal artery
     -+/- ECHO
     -+/- 24hr urinary cortisol and urianry meta
     -Renin and also
     -Sleep study
     -+/- 24hr urinary cortisol and urianry meta
     -Renal U/S with Doppler – CT renal artery
     -+/- 24hr urinary cortisol and urianry meta

2017 AHA Guidelines:

Screening for secondary causes of hypertension is necessary for:

  • new-onset or uncontrolled hypertension in adults including drug-resistant (≥3 drugs)
  • Abrupt onset
  • Age <30 years
  • Excessive target organ damage (cerebral vascular disease, retinopathy, left ventricular hypertrophy, HF with preserved ejection fraction [HFpEF] and HF with reserved EF [HFrEF], coronary artery disease [CAD], chronic kidney disease [CKD], peripheral artery disease, albuminuria)
  • Onset of diastolic hypertension in older adults or in the presence of unprovoked or excessive hypokalemia.


  • Screening includes testing for
    • CKD
    • Renovascular disease
    • Primary aldosteronism,
    • Obstructive sleep apnea
    • Drug-induced hypertension (nonsteroidal anti-inflammatory drugs, steroids/androgens, decongestants, caffeine, monoamine oxidase inhibitors)
    • Alcohol-induced hypertension.
    • If more specific clinical characteristics are present, screening for uncommon causes of secondary hypertension is indicated (pheochromocytoma, Cushing’s syndrome, congenital adrenal hyperplasia, hypothyroidism, hyperthyroidism, and aortic coarctation).



  • 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2017;Nov 13:[Epub ahead of print].
  • Viera AJ & Neutze DM. (2010). Diagnosis of secondary hypertension: An age-based approach. American Family Physician. Dec 15.


ZSFG AM Report Pearls 3/12/18: Lung in a Box: Approach to Hypoxemia (Shout Out to Dr. Richard Schwartzstein @ BIDMC)

Thank you to our MICU team who presented a case of a patient with history of DVT/PE, on anticoagulation who presented with acute hypoxemia and tachycardia. This case gave us an opportunity to think carefully about our differential diagnosis for hypoxemia, which reminded me of the good ole’ days with Dr. Richard Schwartzstein who taught me everything I know about pressures in the lung from his famous alveoli/lung in a box models! We also learned about a standard approach to hypoxemia.


First, check out these great flow charts from Dr. Rabih Geha who demonstrates several super helpful ways of thinking about hypoxemia

Second, let’s remember our DDx based on Aa gradient:

Normal Aa Gradient

  • Hypoventilation
  • Decreased FiO2


Elevated Aa Gradient

  • Shunt
  • V/Q Mismatch
  • Decreased diffusion


ZSFG AM Report Pearls 3/9/2018: Swish Swish Bish, Another Clot in the Vessels: A Review of Portal Vein Thrombosis (PVT)

Hey Team, on this day, we spoke about a person with Hep C and HCC who presented with abdominal pain. They patient was ultimately found to have a portal vein thrombosis. This topic has been extensively covered on the Chiefs Blog, so I thought I would take advantage of this opportunity to collate some of the blog posts. Hope you find this helpful.



  • Common in cirrhotic patients (prevalence ranging between 4.4 – 25%), although rare in compensated cirrhosis (<1%)
  • Important to distinguish between PVT in cirrhotic vs. non-cirrhotic patients b/c etiologies are very different
    • Among non-cirrhotic PVTs, myeloproliferative disorders are implicated in up to 40% of cases!
Clinical presentation: 
  • Varies depending on acute vs. chronic PVT!
  • Acute PVT can present with abdominal pain/distention, fever, n/v/diarrhea, bleeding, lactic acidosis, splenomegaly, sepsis,
    • Acute PVT is often characterized by acute onset abdominal or low back pain.
    • A marked SIRS response is common with elevated acute phase reactants.
    • Liver function is usually preserved. 
    • However, a transient, moderate increase in transaminases can be seen in some patients.
    • Acute PVT is diagnosed with Abdominal CT w/ contrast or Ultrasound with Doppler
    • Expert opinion recommends treating acute PVT with anticoagulation for at least 3 months, but supporting evidence is not as strong as it is for acute DVT
  • Chronic PVT can be asymptomatic or present with varices, ascites, splenomegaly
    • Chronic PVT, the obstructed portal vein is replaced by a network of collateral veins that circumvents the thrombus. 
    • Symptoms are far less common than in acute PVT
    • Diagnosis is often made after a finding of hypersplenism or portal hypertension
    • Liver tests are typically normal in the absence of underlying liver disease
    • Diagnosis can be made with abdominal imaging (US/CT/MRI)
    • Patients with chronic PVT should be screened for esophageal varices (due to high likelihood of portal hypertension)
    • The increased risk of bleeding 2/2 portal hypertension makes anticoagulation more concerning in chronic PVT
    • Data is lacking, but expert opinion suggests anticoagulation should be considered only in patients without cirrhosis and with a permanent risk factor for venous thrombosis that cannot be otherwise corrected
  • Imaging: CT w/ & w/o contrast for confirming diagnosis of acute PVT
    • consider septic portal vein thrombosis in patients with acute PVT and high fever
    • chronic PVTs are often detected on U/S with Dopplers (sens/specificity b/w 60-100%)
  • Labs: In portal vein thrombosis, AST/ALT are usually NORMAL. In contrast to Budd-Chiari where usually very high AST/ALT
  • Anticoagulation is controversial in both acute & chronic PVTs and there are no good RCTs – decision made on a case-by-case basis considering comorbidities
    • Consider treatment more for acute PVTs rather than for chronic PVTs (class IIa evidence)
    • Duration of anticoagulation is shorter if risk factors are transient, otherwise indefinite.
  • Intestinal ischemia
  • Acute pylephlebitis
  • Pportal HTN
  • Cholangiopathy
Other Considerations:
  • The most common local risk factors for PVT are malignant tumors in the portal venous territory and cirrhosis.
  • A local inflammatory foci is another common risk factor (e.g. pancreatitis).
  • An inherited or acquired prothrombotic condition is a general risk factor found in many patients with PVT.
    • Local (30% of cases): inflammatory disease (e.g.. pancreatitis, IBD, cholangitis), infectious diseases (abdominal sepsis), surgery, trauma, cirrhosis, malignancies
    • Systemic (70% of cases): myeloproliferative disease, OCP use, inherited thrombophilias, paroxysmal nocturnal hemoglobinuria
      • portal vein thrombosis is frequently the first manifestation of a chronic myeloproliferative disease (CMPD) (identified in 25-30% of patients); it can be difficult to diagnose given acute alterations in the blood cell counts during acute thrombosis and the finding that many patients present with a masked or atypical myeloproliferative disorder
      • Jak2 V617F mutation is highly specific diagnostic marker of CMPD (because it is not detected in healthy individuals), although it can be absent in 20-60% of patients with chronic myeloproliferative disorders
Anticoagulation beneficial to increase recanalization rates and prevent complication of intestinal infarction (as opposed to unclear indication for anticoagulation with chronic portal vein thrombosis


  • DeLeve et al. Vascular Disorders of the Liver. Hepatology 2009;49(5):1729-1756. PMID:19399912
  • Spaander: Portal Vein Thombosis in non cirrhotic patients. Optima Grafische Communicatie. Dec 2010.
  • Primignani M, Barosi G, Bergamaschi G, Gianelli U, Fabris F, Reati R, et al. Role of the JAK2 mutationin the diagnosis of chronic myeloproliferative disorders in splanchnic vein thrombosis. Hepatology. 2006 Dec; 44(6): 1528‑34.


ZSFG AM Report Pearls 3/8/18: ‘Cause My Heart Starts Beating in Brugada Time With Thoughts of Syncopizing on My Mind: Brugada Pattern and Syndrome

Thank you to Sebastian for presenting a case of a young man with near syncope whose case raised the issue of evaluating an EKG for Brugada sign and contemplating the diagnosis of Brugada syndrome.


Shout Out to Lekshmi Santhosh for these awesome pearls on Brugada that I am reposting and adding a little to.

Brugada Pattern on EKG:

  • The right precordial leads, V1 to V3, display a positive deflection (R’ or prominent J wave) follwed by an elevated down-sloping ST segment elevation and a negative T wave with a normal or even short QT interval.
  • QRS is normal but QT dispersion between V2 and V6 is larger than normal (120 ms)
Brugada Syndrome vs. Brugada Pattern:
  • Patients with typical EKG features who are asymptomatic and have no other clinical criteria have Brugada pattern
  • Patients with typical EKG features who have experienced sudden cardiac death, documented VT/VF, family history of sudden cardiac death <45 years old, syncope, inducible VT, or ventricular tachyarrhythmia have Brugada syndrome
  • Pathogenesis: An autosomal dominant disorder with variable expression – gene mutations in SCN genes (subunits of a cardiac sodium channel)
  • AFib risk: Incidence of Afib is ~10-20% in patients with Brugada syndrome in some studies
  • Risk stratification: After identifying a patient with Brugada syndrome, further diagnostic testing is needed:
    • Genetic testing for SCN mutations and family screenining/genetic counseling
    • Consider EP testing and consideration for ICD implantation based on specific criteria
    • However, no treatment is recommended for asymptomaticpatients w/ Brugada pattern on EKG but no Brugada syndrome
    • This graphic shows how raising V1 and V2 to the 2nd intercostal spaces increases the sensitivity of detection of Brugada pattern on EKG – great clinical pearl.
    • Epidemiology: Rare with prevalence of 0.1-1% of the general population, M > F
  • Great review article here from JACC – enjoy!

Source: Gussak I et al. 1999. The brugada syndrome: clinical, electrophysiologic and genetic aspects. JACC. 33(1):5-15.




ZSFG AM Report Pearls 3/7/2018: Get Up, Stand Up, C’Mon Use That Bup Up! Opioid Metabolism and Why We Love Buprenorphine

Doing a little catch up with AM Report Pearls, but there is so much good stuff going on at ZSFG that I have to share with everyone! On this day, we learned more about the heightened dangers of Fentanyl and some pearls about initiating Methadone Maintenance and talked about the benefits of Buprenorphine for treatment of opioid use disorder.


Pearls About Opioid Metabolism:
  1. For respiratory depression effect: Fentanyl >>>>>> Other Opioids
  2. Methadone is longest acting opioid (half-life is variable but between 8-59!!! hours)
  3. Many medications can interfere with metabolism of Methadone (both enzyme inducers – decrease effect, and enzyme inhibitors – increase effect). Antifungals are notorious for causing DECREASED METHADONE METABOLISM
Pearls About Treatment of Opioid Use Disorder:
  1. Methadone dosing for chronic maintenance therapy for opioid use disorder is 80-100mg
  2. Always confirm the last dose with their methadone program
  3. When discharging a patient on methadone maintenance therapy, CALL their methadone program to let them know that they were in the hospital and let them know if you made any changes
  4. DO NOT discharge them with a plan for them to miss a dose (i.e. discharge on Saturday and cannot initiate on Sunday
Why We Love Buprenorphine:
  • Increasing doses of Buprenorphine do not come with increasing respiratory depression
  • Increasing doses of Buprenorphine do come with increasing analgesia
  • Dahan A. (2006). Opioid-induced respiratory effects: new data on buprenorphine. Palliative Medicine. 20:s3-s8.
  • Dahan A et al. (2006). Buprenorphine induces ceiling in respiratory depression but not in analgesia. British Journal of Anaesthesia. 96(5):627-632.