VA ICU report 6.23.17: Burns and shock!

Case summary

Thanks to Vijay and the ICU team for presenting a great case of a 68M w/ diabetic neuropathy who presented with thermal burns to the legs c/b by likely septic shock.

Top pearls.

  • Superficial skin conditions (e.g. cellulitis) rarely lead to hemodynamic comprise. The presence of systemic illness should prompt consideration for a deeper space process (e.g necrotizing fasciitis).
  • For patients with burns:
  1. Calculate the affected BSA and assess depth of skin involvement
  2. Use the Parkland Formula for fluid repletion
  3. Contact surgery early
  4. Consider transfer to a burn center
  • On initial assessment, four categories of shock (distributive, hypovolemic, cardiogenic and obstructive) can be sorted by SVR (cold skin –> high SVR; warm skin –> low SVR) and JVP.


Assessing the extent of skin involvement (body surface area and depth) is the an important initial step

  • Use the rule of 9’s to estimate BSA involved
    • 9%: head + neck, upper extremity
    • 18%: lower extremity, torso, back
  • Estimate the depth of involvement Burns.png


  1. Consult surgery early
    • Early debridement (< 1 week) reduces risk of super-infection
    • Early consideration of escharotomy reduces risk of compartment syndrome from the edema that naturally follows a burn injury.
  2. Use the Parkland formula to calculate fluid requirements
  3. Consider transfer to a burn center. Some criteria include (full list on UpTodate):
    • Full thickness burn on BSA > 10%
    • Involvement of the face, hands, feet, genitals or joints
    • Third degree burns


Determining the etiology of shock is critical for management.  This is often made easier when data from invasive monitoring is available (SvO2, CVP etc).

On the initial assessmentgauging the SVR (warm skin –> low SVR; cool –> high SVR) and the JVP provide strong clues to etiology of shock.

Shock INitial.png

Shock Approach.png




Moffittt Pearls 6.23.17 – Medicine Report

Thank you to Daniel Kwon for presenting a case of a older gentleman with ESRD, NAFL cirrhosis with HCC presenting with sepsis and RUQ pain 1 week after receiving nivolumab. On imaging he was found to have gas within the liver parenchyma in addition to gram positive rod bacteremia, inspiring HH to take to the board for an approach to GPR (more details below)!



  • Nivolumab is an example of immune checkpoint blockade that acts by blocking a negative regulator (PD-1) of T-cell activation and response, thus allowing the immune system to attack the tumor.
  • As the PD-1 inhibitors become more broadly used, we are seeing new immune-mediated complications of therapy.
  • The differential for GPR bacteremia can be guided by the appearance of the rods – with a clear distinction between filamentous (long & sleek) and non-filamentous rods (short & stout). Call the lab to get a head-start on your diagnosis based on the appearance of the rods!


PD-1 Inhibitors


PD-1 (programmed cell death 1) and its association with the ligand (PD-L1) is a necessary step in stimulating apoptosis of T-cells, serving as an immune checkpoint. PD-L1 is generally expressed by native cells, signaling to the T-cell “I’m one of you! Don’t hurt me”.  Some tumors have been found to also express PD-L1, enabling them to evade destruction by T-cells.  In order to treat these malignancies, PD-1 inhibitors (pembrolizumab, nivolumab) serve to block the interaction between PD-1 and PD-L1, enabling T-cells to stay “programmed on”, and thus enable immune-mediated destruction of tumor.

Because of this mechanism of action, a common consequence is the upregulation of cell-mediated immunity and, unfortunately, inhibition of native tissues to turn off T-cells. As a result, we commonly see autoimmune-mediated inflammation manifested as new rash, diabetes, thyroid disease, pneumonitis, hepatitis, colitis, etc.

Nivolumab – Drug Information

According to the FDA, Nivolumab is a human IgG4 anti-PD-1 monoclonal antibody. It is first line treatment for inoperable or metastatic melanoma, as a second-line treatment for squamous non-small cell lung cancer, and as a second-line treatment for renal cell carcinoma.

Common Immune-Mediated Toxicities Seen with Check-point Inhibition:

Organ System Manifestation Management
Skin & Mucosa Pruritic rash (most common!)




Topical corticosteroids

Oral antipruritics

Consider oral steroids

GI Tract Diarrhea/colitis – presents ~6wks into treatment R/O infxn

Anti-motility agents

Steroids if severe

Liver Hepatitis (rate <5%, severe toxicity very rare) Stop therapy if moderate-severe.

Steroids + mycophenolate given rarely.

Lung Pneumonitis – (rate <5%, but occasionally fatal) Steroids common. Infliximab, cyclophosphamide also used, though patients requiring therapy beyond steroids have nearly 100% mortality.
Endocrine Hypophysitis

Autoimmune thyroid disease

Adrenal Insufficiency T1 DM

Hormonal replacement


Less commonly reported immune-mediated adverse events include the following: acute renal injury, pancreatitis, neurotoxicity (GBS, myasthenia gravis, PRES, aseptic meningitis, autoimmune encephalitis), cardiotoxicity (myocarditis), hematologic (cytopenias), and ocular inflammation.

Many of the adverse events described above can be managed with continued use of PD-1 inhibitors if mild. However, for severe adverse reactions, PD-1 inhibitors are withheld and potential discontinued permanently.

 A Simple Approach to Gram Positive Rods (courtesy of HH!)

  Aerobic Anaerobic

(long & sleek)




(short & stout)




“professional” AFBs*

Clostridium perfringens




* Also stains Acid-Fast



VA Report 6.20: Leukocytosis and Cecal mass

Case Summary

Thanks to Kendra Wulczyn for presenting an amazing case of a 68M w/ COPD who was found down, and found to have a leukocytosis and a cecal mass ultimately diagnosed with diffuse large B-cell lymphoma.

Top pearls 

1. C.diff PCR cannot distinguish between colonization and infection. Approximately 10% of the population is estimated be colonized with C.diff

2.  Neutrophilic leukocytosis usually represents infection. Other causes of polyclonal neutrophilia include drugs, autoimmune disease, and malignancy. Rarely, monoclonal neutrophilia occurs from myeloproliferative diseases.

3. The differential diagnosis of a cecal mass is extensive. Carefully consider structures adjacent to the cecum that may mimic a cecal mass (psoas abscess, tubo-ovarian abscess)

Neutrophilic Leukocytosis

The vast majority of neutrophilic leukocytosis is infection. If an extensive search for infection is negative, consider the following list of non-infectious causes of neutrophilic leukocytosis.

*While you diligently rule out infection, the smear can provide clues to a non-infectious cause (e.g basophilia/eosinophilia may suggest myeloproliferative disease).


Lymphocytic Leukocytosis

Rarely, the leukocytosis will be predominantly lymphocytic:


Cecal Thickening

The differential diagnosis of cecal thickening is extensive, partly because of variety of structures adjacent to the cecum : ileum, lymph nodes, and appendix.

Before proceeding down the cecal thickening pathway, consider (and talk to your radiologist) processes adjacent to the cecum that can mimic a cecal mass (psoas abscess, tubo-ovarian abscess)



Moffitt Pearls 6.20.2017 – Cardiology Report – MINOCA and Heart Failure

Thank you to Caroline for presenting a diagnostic mystery in Cardiology report. She presented a middle aged woman born in Russia presenting with progressive shortness of breath, PND and orthopnea found to have new heart failure. Despite some mild evidence of wall motion abnormalities and an EF of 35% she had nonobstructive CAD on diagnostic ! We discussed the possibilities which include microvascualr disease and Takotsubo cardiomyopathy which both fall under the bucket category known as MINOCA or Myocardial infarction with nonobstructive coronary arteries (see article below)!!



  1. Approach to new heart failure starts with 2 broad categories: ischemic vs. non-ischemic.
    1. Top 4 causes of heart failure include the following: 1) CAD 2) HTN 3) Valve disease 4) Toxin/EtoH
  2. Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a large bucket term that includes many diagnoses: Coronary spasm, coronary, microvascular dysfunction,
    1. Occurs in as many as 10% of patients and represents a condundrum because the underlying cause of their MI is not immediately apparent.
    2. Further work-up for these patient include cardiac MR

 Approach to new heart failure:

  • Ischemic (40% of new heart failure in older series)
    • CAD
    • bridge
  • Nonischemic
    • HTN (11% of new heart failure)
    • Toxic: EtOH, cocaine, other stimulants (up to 5% – though EtOH probably under-recognized as much HTN heart disease may be explained by chronic EtOH use as well)
    • Other meds: classically doxirubicin
    • Valvular (12% of new heart failure): AR, AS, MR
    • Infiltrative: sarcoid, amyloid, hemochromatosis
    • Infectious: post-myocarditis (often viral) up to 10% of cases, Chagas, HIV (4%)
    • Arrhythmia: tachycardia-mediated
    • High output:
      • Anemia
      • Hyperthyroidism
      • Beriberi
      • AV fistulas
        • Congenital: hepatic hemangiomas, HHT
        • Acquired: ESRD
      • Paget’s disease
      • Pregnancy
    • Post-partum Cardiomyopathy
    • Hypothyroidism
    • Stress-induced
    • Untreated OSA
    • Connective Tissue Disease
    • Idiopathic – in some series up to 50% of cases!

Another approach to the etiology of heart failure is by classification of cardiomyopathy as seen on TTE:

  • Hypertrophic cardiomyopathy
  • Dilated cardiomyopathy
  • Restrictive cardiomyopathy
  • Arrhythmogenic right ventricular cardiomyopathy
  • Left ventricular noncompaction

Common First Pass Assessment of New Heart Failure:

  • History – special focus on HF symptoms, arrhythmias, presyncope, syncope, family history
  • Physical Exam – special attention to cardiac and skeletal muscle
  • TTE, ECG
  • Labs: CBC, BMP, LFTs, TSH, HIV, Utox, iron studies
  • Risk assessment: lipid profile, diabetes screen
  • Evaluation for ischemia – coronary angiography

Second Pass for New Heart Failure (often guided by findings noted in first pass):

  • Further evaluation for arrhythmia: Event monitor
  • Advanced imaging: Stress TTE (to assess for increased LVOT gradient in the setting of increased cardiac output), Perfusion scan, Cardiac MRI

MINOCA or Myocardial infarction with nonobstructive coronary arteries

Definition: Presence of acute myocardial infarction in the absence of CAD > 50%

Prevalence: A recent systemic review of the published literature using a < 50% stenosis threshold for MINOCA reported a prevalence of 6% (Pasupathy S, Air T, Dreyer RP, et al. Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries. Circulation 2015;131:861–70.)

Although there are diagnostic criteria, this should NOT be considered a final diagnosis, but a ‘working’ diagnosis that incudes the following aetiologies:


Further Evaluation: Cardiac MRI should be the initial diagnostic study to identify the underlying cause of MINOCA. In as many as 87% of patients with MINOCA a diagnosis is made with cardiac MR.

European Cardiology Article outlining MINOCA:


ZSFG AM Report Pearls 6/19/2017: SHOCK – Differentiating Etiology and Treatment of Cardiogenic Shock

Thanks to Chloe Ciccariello for presenting a case of afib with RVR found to have cardiogenic shock and new onset heart failure.


Top Pearls:

  • When working up new Afib, work up should include considering your “T’s and E’s.” T = Thyroid studies, Troponin. E = EKG and ECHO.
  • ScVO2 (central venous oxygen saturation) is an oxygen SATURATION (not a PaO2) and can be used to differentiate cardiogenic shock from distributive shock. It is measured from a blood draw from a central catheter (often in the SVC), and it is a surrogate for SVO2 (mixed venous oxygen saturation).
  • Norepinephrine can be used as a vasopressor in cardiogenic shock for rapid, initial circulatory support especially if shock is not completely differentiated (See reference below).




  • Hypotension (although can be mild) = typically SBP <90mmHg, MAP <70mmHg with tachycardia
  • Tissue Hypoperfusion (think 3 organ systems)
    • Skin – cold, clammy, cyanotic (low-flow state, i.e. cardiogenic) or warm, diaphoretic (vasodilation, i.e. sepsis)
    • Kidneys – low urine output, i.e. less than 0.5cc/kg/hr or elevated Cr
    • Brain – altered mental status
  • Elevated lactate – a sign of abnormal cellular oxygen metabolism


Type of Shock Preload Afterload (SVR) Cardiac Output
Cardiogenic Low High Low
Distributive Low Low High (but can get low)
Hypovolemic Low High Low
Obstructive High or Low Low Low

Tips on Differentiating:

  • Warm extremities (septic, distributive) vs. cold extremities (cardiogenic, obstructive, hypovolemic)
  • ScVO2 (central venous oxygen saturation) = Low (low cardiac output), High (high cardiac output)
  • Volume Exam – (edema, elevated JVP to point to elevated R-sided cardiac pressures)
  • Limited U/S Exam (Volume – IVC, JVP, cardiac function)


Brief Discussion of Pressors in Cardiogenic Shock:

  • A question was raised about whether Norephinephrine can be used in cardiogenic shock. A 2010 trial compared norepi to dopamine, but it did not have a comparison group to inodilators (dobutamine and milrinone) in the study which are also used in cardiogenic shock.
  • Some authors would advocate that an inopressor (norepi, epi, dopamine (high dose)) would be indicated for circulatory support when a patient’s MAPs are very low and you are worried about the vasodilatory effect of inodilators.
  • In a trial of 1679 patients with circulatory shock from VARYING etiologies, who were randomly assigned to initial therapy with either dopamine or norepinephrine, there was a trend toward a higher rater of death at 28 days with dopamine and there were significantly more arrhythmias, predominantly atrial fibrillation. No difference in the treatment effect based on shock type, including the 280 patients with cardiogenic shock.



  • De Backer et al. (2010). Comparison of dopamine and norepinephrine in the treatment of shock. NEJM 363(9): 779.
  • Vincent JL and De Backer D. (2013). Circulatory Shock. NEJM 369: 1725-1734.

Evernote link:

VA Morning report 6.19.17: Puffy hands syndrome

Case summary: Ivan de Kouchkovsky presented a case with a unique presenting complaint that generated tons of great learning this morning of a 73M with metastatic, castrate-resistant prostate cancer who presented with bilateral upper extremity edema and contractures.
Top pearls: 
1) Bonus pearl from the daily ditty: wall thickness can help you distinguish bulla (<1mm) versus cyst (1-4mm) versus cavity (>4mm) on chest CT.
2) There is a real diagnosis called “puffy hands syndrome”! This usually refers to IVDU-related bilateral hand swelling, however, a host of rheumatologic and other diseases can present with this finding.
3) The instances in which patients with heart failure can have low-normal BNP (~100) are: obesity, isolated R heart failure, and pericardial effusion.

Cystic lung disease:
  • Recall that cystic lung diseases are an important cause of pneumothorax
  • Nifty nomenclature based on wall thickness on CT chest
Wall thickness
bulla (bleb if at parenchyma surface)

Differential diagnosis of bilateral swollen digits or “puffy hands syndrome”:
  • chronic IVDU (causes sclerosis leading to lymphedema)
  • CPPD
  • gout
  • infectious tenosynovitis
  • reflex sympathetic dystrophy
  • eosinophilic fasciitis
  • palmar fasciitis-polyarthritis
  • palmar fibromatosis
  • HCV arthropathy
  • amyloidosis
  • cryoglobulimemia
  • diabetic cheiroarthropathy
  • RS3PE syndrome (remitting seronegative symmetrical synovitis with pitting edema)
  • early scleroderma
  • rheumatoid arthritis
  • paraneoplatic inflammatory arthritis
  • medication reaction
Note that Stemmer’s sign is a physical exam finding characterized by an inability to pinch or lift the thickened skin fold at the base of an affected digit and is found in lymphedema.
Del Giudice P, Durant J, Dellamonica P. Hand Edema and Acrocyanosis: “Puffy Hand Syndrome”. Arch Dermatol. 2006;142(8):1065-1086.
Alexandroff, BL, et al. Woody hands. Lancet, 361 (2003), p. 1344.

HF + low-normal BNP (~100):
  • obesity
  • isolated R heart failure
  • pericardial effusion
Note that Entresto (sacubitril/valsartan), in contrast, will artificially elevate the BNP, as it prevents cleavage.

Moffitt Pearls 6.19.2017 – Rheumatology Report

Thank you to Vincent (our pulmonary fellow) for presenting a fascinating case of a young man with who was otherwise healthy presenting with muscle pain and hemoptysis found to have diffusive GGOs and cavitary nodular opacities. We discussed evaluation of hemoptysis in addition to pulmonary-renal syndromes. Final diagnosis was GPA!!


  1. Massive hemoptysis is defined as either ≥500 mL of expectorated blood over a 24 hour period or bleeding at a rate ≥100 mL/hour.
  2. CT Approach to Hemoptysis
    1. Diffuse – corresponds with DAH
      1. Inflammatory – capillaritis
      2. Non-inflammatory or bland – cardio-pulmonary
    2. Focal
      1. Vascular: PE, AVM
      2. Nodular/Cavity lesions: Infection, Neoplasm, Rheum
      3. Mass – malignancy
      4. Septic emboli
  3. For evaluation of DAH consider CTPE as first line imaging study – You’ll get the information from the non-contrast series PLUS the addition of contrast will help r/o PE, possibly identify AVMs and provide a potential target for future interventions if needed.


Evaluation of Hemoptysis

  • Approach to hemoptysis: airways disease (most common), pulmonary parenchymal disease, or pulmonary vascular disease, or may be idiopathic
  • CT Approach to Hemoptysis
    • Diffuse – DAH (capillaritis, vasculitis), cardio-pulmonary edema
    • Focal – Cavity, AVM, bronchiectasis,
  • Massive hemoptysis as either ≥500 mL of expectorated blood over a 24 hour period or bleeding at a rate ≥100 mL/hour.
  • History: include age, smoking history, duration and quantity of hemoptysis, and association with symptoms of acute bronchitis or an acute exacerbation of chronic bronchitis or bronchiectasis (change in sputum, blood streaking superimposed upon purulent sputum)
  • Laboratory studies to consider: Hgb, platelet count, a coagulation profile, urinalysis w/ micro, blood urea nitrogen, plasma creatinine concentration, ESR/CRP and collection of sputum for microbiologic studies.
    • ANCA, ANA, anti-GBM, complement levels
  • Imaging: Can start with CXR, but would quickly move towards CTPE – r/o PE, assess for AVMs and provides a potential target for future interventions if needed
  • DAH diagnosis: gold standard diagnosis is via BAL


Approach to VasculitisBold face indicates can present with a pulmonary-renal syndrome

Small vessel

  • ANCA- associated or “pauci immune”
  1. GPA: c-ANCA
  2. Microscopic polyangitis: p-ANCA
  3. Eosinophilia granulomatosis with polyangitis: p-ANCA
  • Anti-GBM
  • Lupus – low C3/C4
  • Cryoglobulinemic – low C4




Medium vessel

  • PAN –often spares the lung
  • Kawasaki disease

Large vessel

  • Giant cell arteritis
  • Takayasu arteritis

Check out the algorithm below for an approach glomerulonephritis that highlights pulmonary-renal syndromes from Orlando Regional Medical Center:



ANCA Testing

  • Immune-fluorescence testing is ideal, though in some institutions (including our own), results are reported as positivity with a secondary test for the associated antigens (as opposed to describing the location of the immune-fluorescence).
  • At Moffitt, the antigen testing comes back as a quantitative assessment of the circulating antibody to the following antigens:
    • MPO – which generally corresponds to p-ANCA antibodies
    • PR3 – which generally corresponds to c-ANCA antibodies
    • See the associated image from the Cleveland Clinic below
  • c-ANCA is associated with GPA, p-ANCA is associated with MPA and GPA, though is negative in up to 50% of cases!!
  • We don’t usually follow ANCA levels in the setting of flares as this does not correlate well with disease activity