Monthly Journal Club 4/30/2019

We see patients with ischemic strokes pretty frequently as Internists. We will use today’s journal club to go over some basics of acute ischemic stroke management, and the studies behind our management.

We went over CHANCE, POINT, SPARCL, FLAME, and FOCUS in detail, but the hyperlink to the other trials we briefly mentioned are included!

Acute Stroke Management

  • ABC: Airway, breathing circulation
  • History, physical, glucose, O2 sat, EKG, noncon head CT ASAP
  • Determining time last see normal to see if patient is a candidate for tPA
    • 3-4.5 hours
    • Mechanical thrombectomy can be considered 16-24 hours (DAWN, DEFUSE 3)
  • Additional studies as needed depending on pre-test probability
    • TTE, carotid US, etc if needed
  • Things to consider in the acute setting
    • Fluids:
      • Ensure euvolemic, hypovolemic esp in older adults can worsen cerebral blood flow.
    • Hypoglycemia:
      • Severe hypoglycemia can cause neuronal injury, rapidly correct any hypoglycemic state
    • Hyperglycemia:
      • Associated with poor outcome in stroke patients. AHA/ASA guidelines aim for BG 140-180mg/dL
      • SHINE trial: tight glycemic control vs standard of care, no different in outcome
    • Swallow: Dysphagia screen prior to giving oral meds or food, aspiration precautions.
    • Head and body position:
      • Elevated head of the bed to 30 degrees if concerned for elevated intracranial pressure like is ICH, cerebral edema from large ischemic infarction, aspiration, or cardiac/pulm disease
    • Mobilization:
      • Do so after 24 hours after, dec risk of PNA, DVT, PE, pressure sores. Very early < 24 hours mobilization is associated with dec favorable outcome at 3 months (AVERT trial)
    • Fever:
      • Rule out infectious etiology
      • Can be present after brain injury, fever within 24 hours is associated with 2x inc in mortality at one month.
    • Blood pressure
      • Ischemic stroke only
        • Stabilize blood pressure below 180/105 for at least 24 hours if s/p tPA
        • If no tPA, permissive HTN, do not treat the BP unless SBP > 220 or DBP > 120, or if pt has underlying CAD, HF, aortic dissection, hypertensive emergency.
          • Lower BP by no more than 15% in the first 24 hours
          • Rate of blood pressure control will be dependent on vascular imaging, if a large artery stenosis is found, keep BP high to maintain cerebral blood flow.
          • Choice of meds: IV preferred, titratable, precise
            • Labetalol
            • Nicardipine
            • 2nd line: Nitroprusside, inc risk of inc ICP, inc risk of stroke in older folks
        • Secondary prevention
          • Treat any modifiable risk factors
          • DAPT
          • Statin
          • BP control
          • Life style changes
          • Fluoxetine? (FLAME is favorable, FOCUS is not)

DAPT After Stroke

    • Population
      • 5170 Chinese patients with high risk TIA or minor ischemic stroke within 24 hours of sx onset
    • Intervention
      • Combination ASA/Plavix x 21 days, then aspirin
    • Comparison
      • Aspirin alone
    • Outcome
      • 90 day subsequent strokes
        • DAPT associated with 3.5% absolute reduction (8.2% vs 11.7%), NNT 29
      • No difference in bleeding events
    • Comment
      • Main criticism: Chinese patients have a larger proportion of undertreated modifiable stroke risk factors i.e. DM and HTN and greater burden of large vessel cerebrovascular disease. Also Chinese population might have polymorphisms in genes regulating Plavix metabolism.
      • How to apply to US population?
    • Population
      • 4881 US patients within 12 hours of a minor strokes or TIA
    • Intervention
      • 90 days DAPT and then aspirin
    • Comparison
      • Aspirin monotherapy
    • Outcome
      • Ischemic stroke: Absolute risk reduction of 1.5% in the DAPT group
      • Bleeding: Absolute risk increase of 0.5%, NNH 200
    • Comment
      • Generalizable to US population
      • 90 day DAPT vs 21 in CHANCE!
      • Ongoing THALES trial looking at 30-day, but aspirin/ticagrelor vs aspirin


    • Population
      • 4731 patients with prior stroke or TIA
    • Intervention
      • High intensity statin (atorvastatin 80mg daily)
    • Comparison
      • Placebo
    • Outcome
      • Fatal/non-fatal stroke occurrence at 5 years
      • HI Statin group reduced composite primary outcome of fatal or non-fatal stroke at 5 years
      • Overall a 2.2% absolute risk reduction, NNT to prevent one stroke at 5 years is 45.
    • Comment
      • Industry funded
      • Later analyses revealed associated with HI Statin with hemorrhagic stroke
      • Excluded: Non-ambulatory, AF, cardiac emboli, SAH, high LDL > 160 in some centers


  • FLAME (Lancet 2011): Does early administration of fluoxetine in addition to standard therapy improve recovery after an ischemic CVA?
    • Population
      • 113 patients after acute stroke, randomized to early fluoxetine or placebo
    • Intervention
      • Addition of fluoxetine to post stroke secondary prevention 5-10 days after event
    • Comparison
      • Placebo
    • Outcome
      • 90 day FMMS Scores (measurement of motor recovery)
        • Intervention group has better outcome vs the control group on the FMMS (P = 0.003)
    • Comment
      • Small sample size
      • Short follow up
  • FOCUS (Lancet 2018)
    • Population
      • 3127 patients after acute stroke (2-15 days after), mostly ischemic stroke.
    • Intervention
      • Fluoxetine in addition to standard therapy
    • Comparison
      • Placebo
    • Outcome
      • Modified Rankin Scale Scores (mRS) at 6 months
      • No difference between the 2 groups
      • Fluoxetine group has lower rate of depression than placebo (13% vs 17%) but higher rates of bone fractures (2.9% vs 1.5%)
    • Comment
      • Better designed and powered, no benefit in terms of stroke recovery but associated with inc harm.
      • AFFINITY Trial in Australia ongoing, also investigating the use of early SSRI in post-stroke care.

Hypersensitivity Pneumonitis Secondary to… Oyster Mushrooms 4/29/2019

Today we went over a case from the HumanDx Project (Credit goes to Dr. Maki Cronin, SSM Health St. Louis University Hospital). A young woman presents with 5 months of cough, dyspnea, and unintentional weight loss over the past 5 months in setting of working at an in-door oyster mushroom farm for the past 8 months. She was tachycardic and febrile on presentation, with crackles and clubbing on exam. CT revealed e/o fibrosis and GGO, and BAL revealed significant lymphocytosis. This presentation is consistent with a diagnosis of hypersensitivity pneumonitis, and more specifically, mushroom worker’s lung!

Hypersensitivity Pneumonitis (HP)

This condition has many faces/names:

  • Bird fancier’s lung (feathers, bird droppings)
  • Cheese-washer’s lung (Cheese Fancier per Sarasa)
  • Coffee worker’s lung
  • Compost lung (aspergillus)
  • Farmer’s lung (moldy hay)
  • Hot tub lung (hot tubs)
  • Mushroom worker’s lungs (mushroom)
  • Sauna worker’s lungs (contaminated sauna water)
  • Wine-grower’s lung (moldy grapes)


  • 300 known antigens so far, most common (accounting for 75%) are:
    • Farming
    • Birds
    • Water contamination


  • Hypersensitivity to an environmental antigen leading to a type IV hypersensitivity reaction (they love asking these questions on tests for some reason) in genetically susceptible patients
    • Type 1: IgE mediated, immediate onset (min to hours)
      • Ex: Food allergies, PCN allergy, insect sting
    • Type 2: Cytotoxic hypersensitivity, Ab-mediated cell destruction
      • Drug induced cytopenias, Graves thyroiditis
    • Type 3: Immune complex formation
      • Ex: serum sickness, Arthus reactions, vasculitis, drug fever
    • Type 4: Cell-mediated delayed hypersensitivity
      • Activation of T-cells
      • Hours or days after antigen exposure
      • Ex: Tuberculin sensitivity, contact dermatitis, HP
  • Interstitial inflammation and infiltration with lymphocytes, later on granulomas and fibrosis develop over time


  • Acute:
    • Occurs in sensitized pts with high level antigen exposure
    • Fever, chills, cough, chest tightness, dyspnea, nausea 4-8 hours after exposure
    • Exam: Tachypnea, inspiratory crackles, no wheezing
  • Chronic:
    • Occurs in pts with long-term low-level exposure
    • Months to years onset of exertional dyspnea, cough, fatigue, weight loss
    • Clubbing, fevers are uncommon but can happen
    • Over time: Pulmonary fibrosis, resp failure
  • Subacute:
    • Falls between acute and chronic forms


  • A combination of clinical suspicions with exposure history, with assistance of imaging
  • CXR: Neither sensitive nor specific, may show reticular or nodular opacities
  • HRCT: typically shows profuse centrilobular nodules, predominantly GGO, more chronic exposure will lead to fibrosis, traction bronchiectasis
    • Mosaic pattern with areas of GGO is classic
    • More chronic picture leads to fibrosis, which can lead to traction bronchiectasis
    • Bronchiectasis is a chronic condition where the walls of the bronchi are thickened from inflammation and infection.
  • PFT: Can be obstructive, restrictive, or mixed. Obstruction more commonly seen in chronic.
  • BAL: Very sensitive but non-specific.
    • BAL lymphocytosis (often greater than 50%) is helpful but non-specific. Can also see lymphocytosis in COP and NIP but not this high.
  • Biopsy: Rarely done
  • Antigen-specific immunoassays: very high false positive rate, role unclear.


  • Corticosteroids, usually pred 60 1-2 weeks, then tapered over 2-4 weeks for acute/subacute cases
  • Chronic: Longer course of prednisone
  • Remove from environmental exposure ASAP


  • Reversible if detected early and antigen exposure is eliminated
  • Chronic: leads to fibrosis, which is NOT reversible.

Crowned Dens Syndrome!

Thanks to Eric and Naina for presenting the fascinating case of an elderly man who presented to the ER with acute, progressive shoulder and neck pain/stiffness that started after a visit to the dentist, found to have Crowned Dens Syndrome (???!!!) on CT imaging!

Clinical Pearls

  • The exam maneuvers we use to determine nuchal rigidity (neck stiffness, Kernig, Brudzinski signs) are not sensitive for meningitis.  Kernig and Brudzinski, when present, are highly specific.  Jolt accentuation is more useful as a screening tool because it is highly sensitive (>90%) but not very specific (~60%).
  • Make sure to check out Beers list when prescribing new meds for our geriatric patients.
  • For patients presenting with traumatic neck pain, consider using NEXUS or Canadian C spine rules to help you determine whether CT imaging is necessary.
  • Crowned Dens Syndrome is a rare finding in patients with CPPD and refers to deposition of calcium pyrophosphate crystals in and around the atlanto-axial articulation, which resembles a crown on CT imaging (image here).
  • The knee accounts for 50% of all acute CPPD flares.

Nexus criteria

  • No indication for CT if all of the following criteria are met
    • Absence of posterior cervical spine tenderness
    • Normal level of alertness
    • No evidence of intoxication
    • No abnormal neurologic findings
    • No painful distracting injuries

Canadian C-spine Rule

  • Step 1: CT indicated if any of the following are present:
    • Age > 65 years
    • Dangerous mechanism of injury
    • Paresthesias in the extremities
  • Step 2: Assess for low risk factors that allow for safe examination of the cervical spine range of motion
    • Simple rear-end mechanism
    • Sitting position in the ED
    • Ambulatory at any time
    • Delayed onset of neck pain
    • Absence of midline cervical spine tenderness
    • If ALL of these are present proceed to step 3
  • Step 3: Examine range of motion
    • Test active range of motion
    • Perform radiography in patients who are not able to rotate their neck actively 45 degrees both left and right. Patients able to rotate their neck, regardless of pain, do not require imaging


  • Umbrella term that covers
    • Pseudogout: acute synovitis/flare
    • Chondrocalcinosis: radiographic calcification in hyaline and/or fibrocartilage
    • Pyrophosphate arthropathy
  • Epi
    • 4-7% of adults
    • ~50% of those with radiographic findings are >84 years of age
  • Clinical manifestations
    • Asymptomatic (majority)
    • Acute CPP crystal arthritis: self limited acute or subacute attacks of arthritis involving one or several extremity joints. Knee is affected in over 50% of all acute attacks followed by wrists, shoulders, ankles, feet, and elbows.
      • Triggers: Trauma, surgery, severe medical illness. Abnormalities in serum calcium, magnesium, bisphosphonates, hemochromatosis.
    • Chronic CPP arthritis
      • Chronic inflammatory arthritis (5% of cases): resembles RA, multiple joints involved
      • Chronic osteoarthritis: Most prevalent form of symptomatic disease.
    • Severe joint degeneration
    • Spinal involvement
      • Crowned dens syndrome: rare, characterized by severe acute or recurrent axial neck pain, neck and shoulder girdle stiffness, and associated fever, elevated inflammatory markers, and CPP or calcium phosphate crystal deposition on CT in and around the atlanto-axial articulation
        • DDx would include PMR, Milwaukee shoulder (deposition of hydroxyapatite crystals, commonly seen in women >70 years of age) less frequently meningitis, cervical discitis, or inflammatory spondyloarthritis
        • Favorable response to NSAIDs and colchicine

Infective endocarditis

Thanks to Dr. Olivia Lee for letting us know of the case of this middle-aged woman with h/o endometrial cancer s/p TAH/BSO who was BIBA on a 5150 for GD after being found living in her yard.  Her medical clearance work up led to the diagnosis of endocarditis with a large abscess on the mitral valve leading to septic emboli to the brain, spleen, and kidneys as well as vitritis and endophthalmitis.  She was also noted to have an indwelling mediport with a vegetation at its tip, showering emboli into her lungs.  She successfully underwent urgent surgical replacement of her infected/destroyed valve.

Clinical Pearls

  • Use Duke’s criteria to help with your pre-test probability of endocarditis.  If patient meets criteria for definite endocarditis, consider going straight to a TEE.
  • TTE is not sensitive but highly specific for endocarditis.  However, in a patient with concerning clinical features (see next bullet point), a TEE is necessary to evaluate valve condition and plan for surgical intervention.  TTE is more useful if pre-test probability of endocarditis is low.
  • Indications for surgery
    • Valve dysfunction causing heart failure
    • Perivalvular extension with development of abscess, fistula, and/or heart block
    • Fungi or other highly resistant organisms that are difficult to treat with abx alone
    • Persistent bacteremia despite maximal treatment
    • Recurrent embolization with persistent vegetations
    • Large vegetations (>1 cm) with severe valvular regurg
    • S aureus prosthetic valve endocarditis
  • Indications for early surgery:
    • Heart failure
    • Uncontrolled infection
    • Prevention of embolic events
  • Most common cause of death in endocarditis is heart failure.

For a thorough review of endocarditis, please see our previous blog post here.

ECG Report

Some pearls from our ECG report today:

  • DDx for ST elevations on ECG:
    • Pericarditis (diffuse)
    • Ischemic heart disease (MI, Prinzmetal angina, ventricular aneurysm) –> tends to present in one vascular territory
    • LBBB
    • Early report variant (AKA J point elevation)
  • A flutter at its fastest (2:1 block) would have a rate of 150 bpm (meaning atrial rate is 300 bpm).  So if you  have a regular, narrow complex tachycardia that is going faster than 150 bpm, then start thinking AVRT or AVNRT.
  • A rough estimate of maximum SA node rate possible in a patient is 220 – age.
  • If you see a slow a fib with QRS waves at regular intervals, think of dig toxicity!  Because dig increases atrial and ventricular ectopy, the atria start to fibrillate. At the same time, the AV node is being blocked.  So what you are actually seeing on ECG is fibrillating atrium with complete heart block causing a slow junctional escape rhythm.  Keep in mind though that the most common abnormality on ECG for dig toxicity is PVCs.

Bacteroides bacteremia

Some key learning points from our M&M case discussion today:

  • Ertapenem is a slow acting antibiotic and not an ideal empiric treatment in a patient who presents with sepsis or is acutely ill.  So if you want to use a carbapenem for empiric coverage, pick meropenem or imipenem instead.
    • Fun fact: ertapenem is actually more expensive than mero/imi.  The only use for ertapenem is in transitioning patients from hospitalization to home where its daily dosing is more favorable than the TID dosing of meropenem.
  • For diabetic foot ulcers, please refer to our SCVMC algorithm to help you figure out empiric antibiotics.  Simply open the HHSConnect browser and type in diabetic foot in the search bar to pull up the algorithm.
  • If blood cultures take a longer time to speciate (in our patient, over 5 days), expect anaerobes because anaerobes are difficult to culture and are sent out for speciation.  E coli is an organism that should speciate quickly and would grow in aerobic and anaerobic bottles.  If a species is only growing in anaerobic bottles, then it’s probably not E coli.
  • Levofloxacin is the only fluoroquinolone that has a role in outpatient treatment of GNR bacteremia, other fluoroquinolones (like cipro) are less effective.
  • Avoid using fluoroquinolones for empiric treatment of E coli bacteremia or pyelonephritis because our VMC antibiogram shows ~25% resistance with fluoroquinolones.

IgG4 related disease!

Thanks to John for presenting the case of a middle aged man from Vietnam with history of smoking who presented to the hospital with painless jaundice with imaging concerning for malignancy, found to have IgG4 related autoimmune pancreatitis!

Clinical Pearls

  • For imaging of the biliary tree:
    • Ultrasound is best for stones
    • CT is better for parenchymal disease
    • ERCP/MRCP is best for intraductal masses or stones
  • IgG4 related disease is more common in men >50 years of age.  It can affect many organs, similar to sarcoid.
  • It is an inflammatory and fibrotic systemic conditions where organs form tumefactive lesions rich in IgG4 plasma cells.
  • Diagnosis requires biopsy.  Serum IgG levels may be normal even in active disease.  However, a significantly elevated level is highly sensitive/specific (>95%) for IgG4 related disease.
  • Treatment involves steroids + immunomodulating therapy.

Approach to high bilis!

conjugated hyperbili

unconjugate hyperbili

DDx for painless jaundice:

  • Cancer (pancreatic, cholangiocarcinoma)
  • Meds/toxins
  • Viral hepatitis
  • ESLD
  • CHF
  • Hemolysis

IgG4 related disease

  • First described in 2003
  • Majority men (62-83%) and > 50 years of age.
  • Inflammatory and Fibrotic systemic condition where organs have tumefactive (tumor forming) lesions with an infiltrate rich in IgG4 plasma cells and often elevated IgG4 serum levels (but not always!)
  • The pathophys is poorly understood but thought to be a combination of autoimmune and allergic mediated processes.

Clinical features:

  • Subacute onset, typically few systemic signs/symptoms
  • 30% of those with autoimmune pancreatitis also have tubulointerstitial nephritis at presentation.
  • Pancreatic involvement 
    • Manifestations include a uniformly enlarged pancreas (sausage pancreas on imaging), pancreatic mass which can mimic cancer, recurrent pancreatitis, or strictures.
  • Biliary involvement
    • Biliary strictures leading to obstructive jaundice as well as sclerosing cholangitis
  • ANY organ can be affected (eg: thyroiditis, interstitial nephritis, salivary involvement), much like sarcoid

Spectrum of IgG4-related disease

IgG4 spectrum
Source: UpToDate


  • Need tissue biopsy for diagnosis.  Serum serologies are only suggestive.


  • Steroids + immunomodulating therapy.  

Chronic pancreatitis

Etiologies of Chronic Pancreatitis (progressive inflammatory changes in the pancreas that result in permanent structural damage and histologic fibrosis)

  • Alcohol abuse(45%) as well as cigarette use
  • Recurrent acute pancreatitis
  • Genetic (eg: CFTR, SPINK mutations)
  • Chronic ductal obstruction
  • Systemic diseases (eg: SLE, hyperparathyroidism, hypertriglyceridemia)
  • Idiopathic
  • Autoimmune: Can be Type 1 (part of IgG4 related disease) or Type 2 (idiopathic) 

Clinical manifestations of chronic pancreatitis

  • Epigastric abdominal pain most common symptom however
  • Pancreatic insufficiency (only after 90 %of pancreatic function lost) and manifests as steatorrhea and glucose intolerance/diabetes
  • Remember that chronic pancreatitis puts you at increased risk for PANCREATIC CANCER


  • Amylase/Lipase usually NORMAL so not as helpful
  • 72 hour quantitative fecal fat (steatorrhea alone is non-specific!)
  • Fecal elastasehas high sensitivity and specificity for chronic pancreatitis
  • KUB can show calcificationshinting towards chronic pancreatitis and MRCP/ultrasound can show pancreatic duct obstructions, dilations, strictures or fluid collections


  • Alcohol and smoking cessation!
  • Creon supplementation, may also need fat-soluble (A,D,K,E) supplementation
  • Analgesics for abdominal pain which is extremely hard to control. Minimize opioids but may be necessary for refractory pain.
  • Specialized approaches include celiac nerve blocks, endoscopic surgery and surgical resection