12/13 VA report: syncope, carotid dissection

Gracias to Sasha Deutsch-Link for presenting today: a middle aged veteran who came in with four episodes of syncope at rest.

We talked about the four major buckets of syncope:

  • Neurocardiogenic (aka vasovagal – ~20%)
    • Hx: prodrome (sweating, tunnel vision, stressors, emotion)
  • Orthostatic hypotension (10%)
    • Hx: lightheadedness or syncope on standing, recent h/o diarrhea, poor oral intake, etc
    • Causes: hypovolemia/diuretics, deconditioning, autonomic neuropathy (Parkinson’s, Lewy Body Dementia, POTS), DM, EtOH, amyloidosis, CKD
  • Cardiovascular
    • Hx: sudden LOC without prodrome, preceding palpitations, exertional syncope
    • Arrhythmia
      • Bradyarrhythmia: SSS, high-grade AV block, negative chronotropes, PPM malfunction
      • Tachyarrhythmia: VT, SVT, WPW
    • Mechanical:
      • Endocardial/Valvular: AS, MS, PS, prosthetic valve thrombosis, myxoma
      • Myocardial: pump dysfunction from MI or outflow obstruction from HCMP
      • Pericardial: tamponade
      • Vascular: PE, PHT, aortic dissection, ruptured AAA, subclavean steal
  • Neurologic (10%) – seizure, TIA/CVA, vertebrobasilar insufficiency, dissection of cerebral arteries, migraine, narcolepsy
  • Misc: hypoglycemia, hypoxia, anemia, psychogenic
To do in everyone
  • Careful volume and neuro exams
  • Medication review to identify potential culprits (alpha blockers, nitrates, diuretics, antipsychotics, antiarrhythmics, BBs and CCBs)
Tests to consider
  • EKG
  • Troponin (if suspect PE or ACS as cause)
  • ECHO – to rule out structural heart disease
  • Exercise treadmill test – esp with exertional syncope, r/o ischemia
  • Neuro studies (CT, MRI, EEG) – if history is suggestive
High Risk Features (which may warrant admission)
  • Age >60
  • h/o CAD, HF/CMP, valvular or congenital heart disease, arrhythmia
  • Syncope c/w cardiac cause (lack of prodrome, exertional, resultant trauma) or recurrent
  • Complaint of chest pain or dyspnea, abnormal vitals or cardiac exam
  • PPM/ICD in place, abnormal EKG

We also talked briefly about carotid dissection:

  • Occurs more commonly in the extracranial carotids
  • Traumatic
    • MVC, rapid deceleration injuries, TBI; also implicated: vomiting, yoga, painting a ceiling, neck manipulation during anesthesia, ?chiropractor visits, ?respiratory infections
  • Spontaneous
    • Risk fx: Ehlers-Danlos, Marfan’s, osteogenesis imperfecta, AD
  • Can present with neck pain, CN (commonly XII) deficits, pulsatile tinnitus or stroke symptoms
  • Dx: MRA, CTA > carotid U/S (lots of false positives)
  • Tx: depends on the extent of the lesion and any accompanying deficits, but can require surgery vs medical management (anticoagulation/antiplatelet therapy, angioplasty)


  1. Patel R et al. Cervical Carotid Artery Dissection: Current Review of Diagnosis and Treatment. Cardiology in Review 2012.

12/4 Presby report: relapsing fevers, EBV serologies

A big thanks to Robin for presenting the case of an older man who developed high fevers that disappeared and then relapsed, along with cytopenias and LFT abnormalities, and was ultimately diagnosed with Anaplasma. There was a lot of rich discussion during this case!

What defines a fever?

  • Normal body temperature fluctuates throughout the day, with temps lower in the morning (max 98.9F) and higher in the evening (max 99.9F)
    • so whether you call something a fever or not may depend on the time of day; the cutoff of 100.4F that we’ve come to use is in some ways quite arbitrary

There’s no strict definition of ‘relapsing’ fever; there just has to be some fever-free interval (generally at least 24-48h) before the fevers start again.

  • Keep in mind that several etiologic organisms cause fevers in a relapsing pattern, and that there is also an entity called ‘relapsing fever’ which is caused specifically by several Borrelia species

Causes of relapsing fever

  1. Tick-borne relapsing fever (TBRF): caused by Borellia spp (parkeri, turicatae, hermsii) and transmitted by SOFT ticks like Ornithodoros (different from hard ticks like Ixodes which transmit Lyme, Babesia, etc). Main risk factor: rodent exposure
  2. Louse-borne relapsing fever (LBRF): caused by Borellia recurrentis and transmitted by human body louse. Mostly limited to Africa.
  3. Borellia miyamotoi: a newly described pathogen, transmitted by hard ticks which can be contracted in the Northeast US
  4. Leptospirosis
  5. Rare: anaplasma, ehrlichia
  6. Malignant fevers, particularly Pel-Ebstein fevers from Hodgkin’s lymphoma


Lastly, we talked about EBV serology interpretation. Remember that most people get EBV in childhood.

EBV testing has three components: viral capsid antigen (VCA) IgG, VCA IgM and Epstein-Barr Nuclear Antigen (EBNA)

  • The EBNA will stay elevated indefinitely after infection, so if it’s elevated, that indicates past infection
  • If the VCA IgM is elevated and EBNA is not, that likely indicates recent infection
  • The VCA IgG is really ‘corroborative’ and remains elevated after past infection


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Interpretation of EBV serologies

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Source: Mayo Medical Laboratories. Note: *Results indicate infection with EBV at some time (VCA IgG positive). However, the time of the infection cannot be predicted (ie, recent or past) since antibodies to EBNA usually develop after primary infection (recent) or, alternatively, approximately 5% to 10% of patients with EBV never develop antibodies to EBNA (past).



  1. Barbour A. Harrison’s Principles of Internal Medicine. “Relapsing Fevers”.

11/21 Presby report: pulmonary complications of cocaine, cavitary lung lesions

Thanks to Robin Mansour for presenting a great case of a middle aged woman who presented with a cough, chest pain and a 90 lb (!) weight loss, who was found to have several cavitary chest masses

We talked about some of the pulmonary complications of cocaine use:

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Restrepo et al. RSNA Radiographics 2007


Crack lung is a specific term for an acute hemorrhagic alveolitis after crack inhalation, characterized by cough, SOB, hypoxia, fever, bronchospasm and even hemoptysis and focal infiltrates (and diffuse alveolar damage, microscopically)

Remember that cocaine can be adulterated with substances that can cause a variety of toxic effects in and of themselves:

  • Levamisole (a veterinary antihelminthic): can cause P- and C-ANCA+ leukocytoclastic vasculitis
  • Clenbuterol (beta agonist) that can cause hyperglycemia, hypokalemia, tachycardia (which cocaine can also cause)
  • Other ‘cutting’ agents like talc or baking soda can lodge in the pulmonary microcirculation and cause a local granulomatous reaction

What’s the difference between a cavity and a cyst?

  • Cavities tend to be thicker walled: generally we call something with a wall >5mm a cavity, while <5mm is called a cyst
  • Cavity wall thickness can help with figuring out etiology
    • in one study, cavities w/ max wall thickness >15mm were 90% malignant while those <4mm were 95% nonmalignant

Here’s a framework for thinking about cavitary lung lesions:

Screen Shot 2017-11-21 at 11.32.10 AM.png

Derived from Gadkowski et al, Clin Microbio Rev 2008

Lastly, a differential for skin lesions involving tattoos:

  • Sarcoidosis
  • Nontuberculous mycobacteria
  • Discoid lupus
  • Local foreign-body granulomatous skin reaction


  1. Restrepo et al. Pulmonary Complications from Cocaine and Cocaine-based Substances: Imaging Manifestations. RSNA 2007.
  2. Gadkowski et al. Cavitary Pulmonary Disease. Clin Microbio Rev 2008.

11/9 Presby report: a moste curious case of metformin-associated lactic acidosis

Late post because I’m on service (sorry!).

A huge thanks to recent Penn IM alum Geoff Bass for giving a great talk on a middle-aged diabetic man who came in with abdominal pain and was found to have metformin-associated lactic acidosis (MALA).

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Lactate metabolism is intertwined with that of glucose and pyruvate

Hyperlactatemia occurs via one of four mechanisms:

  • Tissue hypoxia
  • Aerobic glycosis (aka glycolysis that depends on factors other than tissue hypoxia (think high-epinephrine states)
    • Sepsis
    • Severe asthma + beta-agonist use
    • Cardiogenic or hemorrhagic shock
    • Pheochromocytoma, cocaine
  • Impaired oxidative phosphorylation
    • Drugs: ARVs, propofol (PRIS), metformin, toxic alcohols, salicylates, cyanide
  • Liver dysfunction
    • the liver normally clears ~70% of whole body lactate, so acute liver dysfunction can lead to elevated serum lactate; but chronic liver disease (ie cirrhosis) usually doesn’t (in the absence of sepsis or some other driver)

Metformin toxicity is generally rare, and usually only occurs in the context of other predisposing conditions: AKI/CKD, liver disease, alcohol use, concurrent critical illness, heart failure

It is a clinical diagnosis, as there is no one test that confirms the diagnosis; you can send off a metformin level, but it takes a while to come back and is generally unhelpful unless it’s totally negative (in which case you should look for other causes)

MALA is mostly treated with conservative measures:

  • Gastric decontamination
  • Supportive care
  • Hemodialysis
    • Consider if lactate >15-20, pH <7.1, or other conditions such as shock, renal failure, etc


  1. DeFonzo R, Fleming GA, Chen K, et al. Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism, 2016 Feb; 65(2): 20-29.

  2. Kraut JA, Madias NE. Lactic Acidosis. NEJM,  2014 Dec 11;371(24):2309-19.

11/13 Presby report: sulfonylurea toxicity, loop diuretics

Thanks to Dan Kim for giving a great talk (and to the audience of contributing lots of great learning points!) on a middle aged woman who presented with hypoglycemia after taking a dose of her sulfonylurea.

Recall that sulfonylureas work by inhibiting the ATP-sensitive potassium channel in pancreatic beta cells; this leads to increased endogenous insulin release. Long acting sulfonylureas (ie glyburide) are more likely than short-acting agents (glipizide, glimepiride) to cause hypoglycemia.

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Symptoms of hypoglycemia; remember that it can mimic virtually any neurologic condition

When thinking about hypoglycemia, it helps to think in terms of whether the patient is ill-looking or not


  • drugs (insulin or insulin secretagogue, alcohol, ?others)
  • Sepsis/critical illness
  • Hormone deficiency (cortisol, glucagon or epinephrine)

Seemingly well-appearing

  • Endogenous hyperinsulinism
    • insulinoma
    • post-gastric bypass hypoglycemia
    • antibodies to insulin or insulin receptor
  • Surreptitious/factitious hypoglycemia


Sulfonylurea toxicity is generally a clinical diagnosis based on history. There are sulfonylurea assays that can be sent, but they generally take too long to result and are thus of limited use

Management of sulfonylurea toxicity

  • D50
  • D5 or D10 gtt
    • should not be used as monotherapy for sulfonylurea toxicity, as it will cause transient hyperglycemia that triggers insulin release and further episodes of hypoglycemia
  • Octreotide
    • works by decreasing insulin release from beta cells
    • Give for the first 24h, and then stop; can restart if hypoglycemia recurs
  • Glucagon
    • NB: very short acting, so should only be used as a temporizing measure while getting IV access or some other longer-acting source of glucose

Activated charcoal can be used within 2-3h of the ingestion, but hemodialysis has not been shown to be effective. Diazoxide, an older drug which also inhibits pancreatic insulin release, used to be used, but is less effective than octreotide and can cause hypotension.


We talked briefly about the threshold effect with loop diuretics:

Screen Shot 2017-11-13 at 1.55.05 PM.png

The inflection point where the blue line takes off is the ‘threshold’, and is largely determined by the rate at which the diuretic gets to its site of action. HF patients show resistance at any given diuretic dose due to Na reabsorption at other segments of the nephron. Brater 1983.

Lastly, this study compared bolus vs continuous infusion of lasix in patients with ADHF, and found that there was no real difference between the two dosing strategies. However, keep in mind that this was part of a research setting, where even bolus doses were probably timed perfectly. In real life, doses may be given late (ie beyond the point that the previous dose is effective), so continuous diuretic infusion may still have a role in clinical practice.


  1. Oh S et al. Loop Diuretics In Clinical Practice. Electrolyte Blood Press 2015.
  2. Felker et al. Diuretic Strategies in Patients with Acute Decompensated Heart Failure. NEJM 2011.
  3. Brater DC, Day B, Burdette A, et al. Kidney Int 1984; 26:183.

11/2 Presby report: summer fever, HACEK endocarditis

Thanks for Dr. Judy O’ Donnell for lending her expertise with the case of an older dentist who came in with several weeks of fevers during the summer, found to have HACEK (H. parainfluenza) endocarditis!

The problem representation of a summer fever can help you create your differential

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Remember the Duke criteria for endocarditis (major criteria boxed in red)

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NEJM 2013

The main indications for surgical treatment of endocarditis are:

  1. Heart failure
  2. Uncontrolled infection (particularly with organisms that won’t clear with just antimicrobial therapy, especially Candida spp)
  3. Prevention of embolization

Ideally, blood cultures should clear before the patient goes to the OR but that is not always possible.

This patient ended up growing Hemophilus parainfluenzae, which is part of the HACEK group of organisms. HACEK bugs used to be poorly culture-able, but with advances in technology, they generally grow out of standard blood culture bottles within 4-5 days.

Certain species are more prone to embolization than others

  • Staph aureus
  • Pneumococcus
  • Group A and Group B strep
  • Candida

Final pearls

  • if you have a normal LP (normal cell counts, etc) but still suspect an infectious cause of non-specific fever, a Lyme PCR and maybe West Nile testing may still be useful as they can occasionally present with a normal LP
  • West Nile Virus can cause a nonspecific febrile illness, although usually <2 weeks in duration
  • mitral valve vegetations are more prone to embolization than other valves because flow across that valve is more turbulent than across other valves


  1. Hoen et al. Infective Endocarditis. NEJM 2013.
  2. Hu et al. Case 24-2015. NEJM 2015.
  3. Mourad et al. A comprehensive evidence-based approach to fever of unknown origin. JAMA 2003.

11/1 Presby report: pancreatic masses, with a helping of chronic diarrhea

Today we discussed the interesting case of a middle aged man with chronic diarrhea who was found to have a pancreatic mass, ultimately found to be a gastrinoma. We spent some time discussing pancreatic masses, as the differential doesn’t just start and end with pancreatic cancer!

Pancreatic masses are not a trivial problem: 2-20% of patients who get MRIs for other reasons will have a pancreatic cysts or other solid lesions!

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Mets to the pancreas are usually from RCC or melanoma, or occasionally ovarian cancer.

Pancreatic cysts vary in their malignant potential

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JAMA 2016



There are 5 questions that will help you work-up chronic diarrhea:

  1. Is it really diarrhea? Make sure it’s not fecal incontinence due to chronic constipation or stool impaction/overflow
  2. Is it medication-induced? Beware of metformin, NSAIDs, PPIs, SSRIs, antibiotics, Mg-containing meds, mycophenolate mofetil; also sorbitol- or xylitol-containing gums, and herbal teas/supplements which contain sennosides or other compounds
  3. Is it factitious? (consider if stool osm <290 or >600, female healthcare worker age ~45)
  4. How long? acute (<2 weeks) vs chronic (>4 weeks) diarrhea
  5. What’s the diarrhea like? inflammatory (frequent/bloody BMs, fever) vs fatty (greasy, hard to flush, weight loss) vs watery diarrhea
Screen Shot 2017-11-01 at 9.51.58 AM.png

Mayo Clinic Proceedings 2012

The majority of people with chronic diarrhea do not need stool cultures! In patients with chronic diarrhea, the highest yield would be in immunosuppressed patients (AIDS, organ transplant, etc), as they are more likely to have prolonged infection with a pathogenic organism like Salmonella or Shigella; this type of prolonged infection just doesn’t happen in immunocompetent individuals.

Other pearls

  • CA 19-9 can be elevated in pancreatic cancer but ALSO in any cause of pancreatic inflammation; so it is very NONSPECIFIC, meaning you shouldn’t jump to order it on anyone with a pancreatic mass
  • Gastrinomas generally don’t require adjuvant chemo after resection since they’re so slow growing
  • Carcinoid tumors will only produce symptoms (flushing etc) once they’ve metastasized to the liver, even if they’re radiographically invisible by CT or MRI
  • Blastocystis hominis is a commonly seen fecal protozoan, but it’s not clear that it truly causes diarrhea; for most people, it’s probably just a bystander to some other cause of diarrhea
  • Fecal calprotectin is secreted by neutrophils, and is a sign of inflammation; it’s most commonly used in IBD, but any cause of inflammatory diarrhea would cause it to be elevated

A lot of this is pulled from Becca’s excellent post from the summer. Take a look at hers for more re: the workup of chronic diarrhea!


  1. AGA Guideline on Diagnosis/Management of Asymptomatic Neoplastic Pancreatic Cysts. 2015.
  2. Stark et al. Pancreatic cystic disease: a review. JAMA 2016.
  3. Sweester S. Evaluating the Patient with Diarrhea: A Case Based Approach. Mayo Clin Proc.June 2012;87(6):596-602.