All posts by alp37

VA ICU Report 10.6.17: Pseudomonas double-coverage + post-arrest neurologic prognostication

Case summary: We discussed the case of 83M with PMH ESRD on HD, CAD s/p CABG, AIN on prednisone, who had a PEA arrest secondary to hypoxemia in the setting of multifocal pneumonia, who developed post-arrest myoclonus and was ultimately transitioned to comfort care. Thanks to Jill Goslinga, Neuro intern extraordinaire, for bringing up tons of great questions and pearls.

Top pearls: 

  1. Data support double-coverage (beta-lactam and aminoglycoside) for Pseudomonas in patients who are critically ill and at risk for multi-drug resistant organisms. Once sensitivities are known, you can narrow appropriately.
  2. Although neurologic prognostication is extremely variable, some 72H coma exam findings are predictive of poor neurologic outcome. These include absent or extensor motor response on day three and/or absent pupillary or corneal reflexes on day three.
  3. James Frank reminded us that nodules on a chest CT should make you expand your infectious differential beyond classic bacterial pathogens, particularly in immunocompromised patients– think carefully about mycobacteria (tuberculous and nontuberculous), endemic fungi (histo, cocci), and (rarely) PCP.

Pseudomonas double-coverage: just the facts

  • These are pearls I’ve learned from Jen Babik’s fantastic “Fever in the ICU” lectures.

Why do we talk about “double-coverage” for Pseudomonas?

1. Concern about resistant Pseudomonas: give 2 ABX EMPIRICALLY to expand the spectrum.

2. Idea of synergy between 2 active ABX: usually beta-lactam + (aminoglycoside or FQ).

  • 2012 metaanalysis showed NO mortality benefit, including for septic shock or neutropenic patients

3. Hope that 2 ABX prevents development of resistance.

  • No evidence that combination therapy prevents development of resistance and may increase superinfection rate.

…So when should we double-cover?

  1. In critically ill patients (like this patient) who have risk factors for multi-drug resistant organisms, consider empiric coverage with 2 ABX with anti-pseudomonal activity. Then narrow pending cultures and susceptibilities.
  2. Check your local sensitivities: the most recent SFVA Pseudomonas sensitivities from 1/2017 (non-urine and urine) can be found here!
  • Note that most studies are observational, non-blinded and have lots of heterogeneity (e.g. different ABX combinations).
  • Also note that these data likely DON’T apply to specific sub-populations at greatly increased risk of resistant organisms (e.g. cystic fibrosis patients).

Jen Babik’s “Fever in the ICU” lectures

Pseudomonas: Paul and Leibovici, CID 2013.(PMID 23580731)

Neurologic prognostication post-arrest

  • We discussed how this is one of the most humbling areas of medicine, as it is incredibly variable and difficult to predict.
  • Thanks so much to Jill Goslinga for digging into the data on the most important neurologic exam findings we and our Neuro colleagues use in our assessment.
  • Two systematic reviews have concluded that two clinical criteria have been found to be 100 percent specific for poor outcome:
    • Absent or extensor motor response on day three
    • Absent pupillary or corneal reflexes on day three
  • A JAMA Rational Clinical Exam review noted 5 clinical signs that strongly predict death or poor neurological outcome:
    • absent corneal reflexes at 24 hours (LR, 12.9; 95% confidence interval [CI], 2.0-68.7),
    • absent pupillary response at 24 hours (LR, 10.2; 95% CI, 1.8-48.6),
    • absent withdrawal response to pain at 24 hours (LR, 4.7; 95% CI, 2.2-9.8),
    • no motor response at 24 hours (LR, 4.9; 95% CI, 1.6-13.0),
    • no motor response at 72 hours (LR, 9.2; 95% CI, 2.1-49.4).
  • Although myoclonic status is associated with poor neurologic outcome, seizures and non-epileptic myoclonus alone are not significant predictors of morbidity or mortality.
    • We often use EEG to evaluate for status for this reason

Neurology. 2006;67(2):203.

Lancet. 1998;352(9143):1808.

JAMA. 2004 Feb 18;291(7):870-9.


VA AM Report 10.2.17: Post-XRT presyncope

Case summary: Thanks to Max Brondfield for presenting the case of a 56M with PMH remote squamous cell carcinoma of the head and neck s/p chemoXRT, who presented with chronic, intermittent presyncope on exertion, found to have bilateral 100% carotid artery occlusion likely 2/2 prior neck XRT.


1. (Pre)syncope in the real world includes getting at least an ECG and orthostatic vital signs. Consider inpatient evaluation and monitoring in patients with cardiovascular disease, abnormal ECG or FH SCD, OR those with recurrent episodes.

2. Thanks to Gerald Hsu for giving us his mental breakdown of complications of radiation therapy. It depends on the geography and dose. Then, you can divide the complications of radiation into long- and short-term sequelae, though time courses are variable.

3. Thanks to Goop for reminding us that carotid ultrasound is not a high value test in the evaluation of syncope and is part of the Choosing Wisely campaign as a consequence.

Syncope (or presyncope) in the real world

  • We discussed that for practical purposes, we tend to lump “presyncope” with syncope given the difficulty in distinguishing between these two entities in real life.
  • See here for a great prior blog post going through the Ddx for syncope (props to C. Auriemma!)
  • Recall that all patients presenting with syncope should (at least) receive:
    • ECG
    • orthostatic vitals
  • Max brought up the complexities of evaluating syncope in the outpatient setting, particularly in urgent care/back-up clinic, especially with regard to who should be hospitalized and who should get more extensive work-up.
  • Features that would support hospitalization for further work-up and monitoring include:
    • cardiovascular disease
    • abnormal ECG
    • FH of sudden cardiac death
  • Importantly, patients with multiple episodes compared with an isolated event are more likely to have a serious underlying disorder, as was the case with this patient.
    • Props to Max for combing through the chart to see that the patient has presented multiple times before with similar symptoms and had had a fairly exhaustive but unrevealing work-up, which prompted him to search for more esoteric etiologies.
  • Carotid U/S (or MRA!) should not be a part of your first-pass work-up for syncope (this has been identified as low value care by the Choosing Wisely campaign)
    • Great JAHA study illustrating the low value of this testing strategy:
      • 16.5% of all Medicare beneficiaries with simple syncope underwent carotid imaging
      • 6.5% of all carotid ultrasounds ordered were for this low-value indication
      • Manual chart review of 313 patients at a large academic medical center who underwent carotid ultrasound for simple syncope over a 5-year period
        • Only 2% of the 313 patients imaged experienced a change in medications after a positive study
        • <1% of patients underwent a carotid revascularization procedure.
    • However, put prior neck XRT should be on your list of causes for early-onset neck vessel atherosclerosis (just as it is for early-onset coronary artery disease in patients who received chest XRT for breast cancer or Hodgkins lymphoma)

Am Fam Physician. 2011 Sep 15;84(6):640-650.

Side effects of XRT

  • When considering radiation complications, Gerald Hsu recommends thinking about:
    • 1) Geography- local/adjacent structures more likely to be affected
    • 2) Dose- higher doses more likely to cause side effects
    • 3) Keep in mind that time course can vary- patients can have late-onset radiation proctitis for example long after prostate XRT
  • Short-term: tissues swell during XRT–> edema, overlying skin changes
    • Abdominal- nausea/vomiting
    • Head and neck- mouth and throat sores
    • Thoracic- esophagitis
    • Pulm- pneumonitis
    • Pelvic- cystitis, proctitis
    • Usually subsides with time
  • Long-term: prior edema and inflammation–> fibrosis
    • Thoracic- cardiomyopathy
    • Pelvic- infertility
    • Head and neck- accelerated carotid artery atherosclerosis/stenosis, hypothyroidism
    • All- secondary cancers, especially skin cancers

Bhandare N, Mendenhall WM (2012) A Literature Review of Late Complications of Radiation Therapy for Head and Neck Cancers: Incidence and Dose Response. J Nucl Med Radiat Ther S2:009. doi:10.4172/2155-9619.S2-009


VA Morning report 9.25.17: Rapid-onset pleural effusion

Case summary: Thanks to Andrew Folick for presenting the high-yield case of a 72M with metastatic melanoma previously treated with both immune checkpoint (pembrolizumab) and BRAF (dabrafenib/trametinib) inhibitors and recent PE on dalteparin, who presented with rapid-onset pleural effusion.


  1. The differential for rapid-onset pleural effusion includes: transudative fluid, hemothorax, chylothorax…and ?reactive effusion from targeted therapies (see below for more details regarding pulmonary complications of these agents!).
  2. Technically, diagnosis of hemothorax on thoracentesis is established if pleural fluid has a Hct >15% or is >50% serum Hct. Practically, it is often based on clinical picture and whether the fluid appears bloody.
  3. Chronic transudative effusions can transition to “exudative” because the protein increases over time. 
  4. Don’t put a chest tube in a patient with a transudative pleural effusion! This inevitably leads to malnutrition and is a portal of entry for infection.

Pulmonary complications of targeted therapy

  • Immune checkpoint inhibitors (e.g. pembrolizumab)
    • Pneumonitis is uncommon (~5% of patients) but can be severe.
    • It’s a diagnosis of exclusion: rule out infection and malignancy-associated pnuemonitis, as well as radiation pneumonitis.
    • Can occur at any time during therapy.
    • 1/3 of patients are asymptomatic, and the most common presenting symptom is cough
    • Imaging characteristics vary widely. There are case reports of pleural effusion associated with a clinical diagnosis pneumonitis, but it’s unclear if this is a drug side effect or a “reactive” response to cancer cell death in response to therapy.Pneumo_antiPD1_PDL1_therapy

This is an especially good UptoDate article

Clin Chest Med. 2017 Jun;38(2):223-232.

  • BRAF inhibitors (e.g. dabrafenib/trametinib)
    • Respiratory complications are extremely rare with vemurafenib or dabrafenib monotherapy.
    • Pneumonitis occurred in 2.4% of patients (5/211) treated with trametinib monotherapy
    • The time course and symptoms of pneumonitis are similar to immune checkpoint inhibitors.

  • General treatment considerations for toxicities associated with targeted therapy
    • For grade 2 (moderate) immune-mediated toxicities, treatment with the checkpoint inhibitor should be withheld and should not be resumed until symptoms or toxicity is grade 1 or less. Corticosteroids (prednisone 0.5 mg/kg/day or equivalent) should be started if symptoms do not resolve within a week.
    • For patients experiencing grade 3 or 4 (severe or life-threatening) immune-mediated toxicities, treatment with the checkpoint inhibitor should be permanently discontinued. High doses of corticosteroids (prednisone 1 to 2 mg/kg/day or equivalent) should be given. When symptoms subside to grade 1 or less, steroids can be gradually tapered over at least one month.

VA AM report 9.19.17: DVT/PE version 3.0

Case summary: Thanks to Adam Tabbaa (double-double) for presenting a case of a 70M with PMH obesity presenting with LLE edema and dyspnea and found to have a PE that made our nerd-hearts sing!

Top pearls:

  1. Anti-coag clinic pearl: for patients with a positive LE ultrasound OR CTPE, getting that second confirmatory imaging study (e.g. either CTPE or LE ultrasound) can seem like overkill. However, for providers who follow patients longitudinally, this additional imaging is useful (e.g. for serial imaging comparison, to monitor clot burden when considering whether to come off of anticoagulation)
  2. The most recent CHEST VTE guidelines recommend DOACs (e.g. apixaban) as FIRST LINE for DVT/PE over vitamin K antagonists except patients with cancer-associated thrombosis (though clinical trials are underway to test DOACs in cancer).
  3. Per a recent NEJM study, there is little benefit to screening for malignancy in unprovoked PE.

Why get an ultrasound in addition to a CTPE? Can be helpful for providers who follow patients longitudinally!

  1. Serial imaging comparison
  2. Helps when trying to get patients OFF anticoagulation (can follow serial U/S)
  3. Helps if patient has subsegmental PE on CTPE (if have a DVT, this supports anticoagulation)

No benefit to screening for malignancy with CT abdomen/pelvis in unprovoked PE

  1. 854 patients randomized to limited cancer screening (basic blood testing, chest radiography, and screening for breast, cervical, and prostate cancer) versus limited + CT A/P. There was no significant difference between the two study groups in the mean time to a cancer diagnosis (4.2 months in the limited-screening group and 4.0 months in the limited-screening-plus-CT group, P=0.88) or in cancer-related mortality (1.4% and 0.9%, P=0.75).



  1. In AT10, the first-line recommended anticoagulant therapy includes dabigatran, rivaroxaban, apixaban, or edoxaban over vitamin K antagonists (VKA) or low molecular weight heparin (LMWH).
  2. The one exception is in patients with cancer-associated thrombosis. In this subset, AT10 recommends LMWH over VKA or DOACs with extended therapy.

PE Risk stratification

  1. Rely on vital signs, biochemical markers, TTE and imaging to risk stratify VTE patients.
  2. Note that degree of clot burden does not factor into risk stratification (as long as PE is segmental).
  3. Here is a nifty risk stratification algorithm.


Management of PE: An Update. J Am Coll Cardiol 2016;67;976-990.

VA Morning report 9.18.17: Myelodysplastic syndrome

Case summary: We chatted about an 83M with PMH mod-severe aortic stenosis (AS) and myelodysplastic syndrome (MDS) who presented with fatigue and was found to have new heart failure from his AS and slowly downtrending hemoglobin. Gerald Hsu made a guest appearance and taught us a ton about MDS!

Top pearls:

  1. Myelodysplastic syndrome (MDS)- a clonal stem cell disorder of ineffective hematopoesis– encompasses a spectrum of phenotypes ranging from asymptomatic patients with macrocytic anemia to transformation to acute myeloid leukemia.
  2. The severity of MDS is based on the magnitude of cytopenias, bone marrow blast percentage, and cytogenetic abnormalities. These are combined into a scoring system called the revised International Prognostic Scoring System (IPSS-R) that divides patients into high- and low-risk categories.
  3. Higher-risk patients are at increased risk of progression to AML and short survival, which directs treatment toward altering the natural history of the disease. For lower-risk patients, the priority is treatment of cytopenias to improve quality of life.

Myelodysplastic syndrome crash course 

  • MDS is the most common myeloid neoplasm in the US, with 15,000 new diagnoses annually
  • Blood smear:
    • Red and white blood cells are most commonly dysplastic
    • Red cells- macrocytosis, ovalomacrocytosis most common but can see elliptocytes, teardrops, acanthocytes (spur cells), basophilic stippling, Howell-Jolly bodies and nucleated reds
    • White blood cells- pseudo-pelter-Huet, which are WBCs with reduced segmentation and granulation


  • You can consider MDS as a spectrum disorder similar to colon cancer
    • Some patients have small hyperplastic polyps that rarely progress to cancer
    • Others have large tubular adenomas that commonly undergo malignant transformation
  • Use the International Prognostic Scoring System (IPSS-R) to stratify MDS patients into low-risk and high-risk categories and direct treatment
    • high-risk patients have a median survival of <1 year
      • survival in high-risk MDS is worse than stage IV non-small cell lung cancer!
      • it’s therefore imperative to start therapy (taking performance status, competing comorbidities, etc. into account)
      • options include: stem cell transplant, hypomethylating agents (e.g. azacitadine) or chemotherapy
    • low-risk patients have a median survival >8 years
      • over half of low risk MDS patients die from something else before succumbing to MDS and/or AML
      • the predominant cytopenia is anemia, which is managed with transfusions and erythropoiesis stimulating agents (e.g. Epo)
      • if patients fail these therapies, hypomethylating agents and lenalidomide can be effective in a minority of patients
    • See these two great articles for more details: low-risk & high-risk


VA Ambulatory Report 8.30.17: Eosinophilia explosion

Case summary:  A post-call but still effervescent Anne Rohlfing presented a fabulous case of a 60M with PMH asthma and aspirin-exacerbated respiratory disorder, who presented with bilateral hand soft tissue swelling and palpable purpura and was found to have marked eosinophilia and CXR consolidations concerning for eGPA!

Top pearls:

  1. Break down bleeding that occurs in the skin or mucus membranes into: 1) palpable purpura (vasculitis), 2) macular (non-palpable) purpura:  petechiae (<3mm, platelet-related) OR ecchymosis (>5mm, trauma, platelet/coagulation-related).
  2. Recall that drug reactions can take many forms, from IgE-mediated anaphylaxis to immune complex deposition.
  3. In cases of SUPER high eosinophilia or the acutely ill patient, the differential diagnosis narrows.

Bleeding in the skin 

  • Here is a FANTASTIC Powerpoint module from the American Academy of Dermatology reviewing the breakdown of bleeding in the skin and mucosal membranes.
  • It can be difficult to distinguish between these (e.g. petechiae can be confluent), however, each is associated with specific diagnoses, so precision is important.
  • Palpable purpura: connotes vessel inflammation (vasculitis)


  • Macular (non-palpable purpura)
    • petechiae – <3mm, associated with platelet bleeding disorders
    • ecchymosis- >5mm, associated with platelet and coagulation bleeding disorders, trauma, thin skin

The low-down on drug reactions

  • We reviewed the takeaways from last week’s fantastic Grand Rounds by UCSF Allergy/Immunologist attending Iris Otani
  • There are 4 types of allergic responses, all of which can occur with drugs:
    • Type I- IgE mediated (anaphylaxis)
    • Type II- non-IgE antibody mediated (hemolysis)
    • Type III Immune complex (serum sickness)
    • Type IV cell-mediated (contact dermatitis)
  • Drug reactions are not all maculopapular rashes! Remember to consider all of these phenotypes when evaluating a patient with a potential drug reaction!

Hypereosinophilia and hypereosinophilic syndromes

  • While there are many causes of peripheral eosinophilia, the degree of elevation AND/OR the acuity of illness can help narrow the diagnosis.
    • Hypereosinophilia= >1.5 x 10^9
    • Hypereosinophilic syndrome= organ infiltration
  • With very high eosinophils or an acutely ill patient, consider:
    • Primary hematologic disease (eosinophilic leukemia, systemic mastocytosis with eosinophilia)
    • Secondary
      • Rheumatologic (eGPA)
      • Paraneoplastic (Lymphoma)
      • Disseminated infection (Strongyloides, Trichinella)
      • Drug hypersensitivity


VA Morning report 8.21.17: Pearls on pulmonary abscess + pulmonary embolism

Case summary: Our intrepid sub-I Michael Khanjyan (with assist from Bennett Caughey) presented a fantastic and classic teaching case that was chock full of pearls. A 52M with DMT2, prior DVT/PE, and pulmonary nodules who presented with subacute B symptoms, dyspnea and cough and was found to have both a pulmonary abscess and pulmonary embolism.

Top pearls:

  1.  LT taught us that pulmonary abscess is extremely unlikely in an edentulous (toothless!) patient, as teeth are the required nidus. Therefore, you should suspect a post-obstructive process in an edentulous patient who presents with subacute pulmonary infectious symptoms.
  2. Use your d-dimer wisely
    1. Only validated in outpatient and ED in patients determined to have low risk VTE by Well’s criteria
    2. Use your age adjusted cut off – if age > 50 then age x 10
  3. If you’re unsure about a pulmonary embolism called overnight, follow-up the final read in the morning, as there is measurable false positive rate for general radiologists compared to chest radiologists.

Pulmonary abscess clinical pearls

  • The illness script for pulmonary abscess is a patient who presents with indolent symptoms (weeks-months) including fever, night sweats, weight loss, cough, sputum production.
  • The vast majority of lung abscesses are caused by aspiration of anaerobes present in gingival crevices.
    • Thus the need for teeth!
    • Other more rare causes (that one might consider in an edentulous patient!) include bronchial obstruction (e.g. from neoplasm) or septic emboli (e.g. from Lemeirre’s disease or tricuspid valve endocarditis)
  • Predisposing factors for aspiration:
    • altered level of consciousness (EtOH, drug abuse, anesthesia, head trauma)
    • dysphagia
  • Consider smelling your patient’s sputum (!), as “putrid” odor is considered diagnostic of anaerobic bacterial infection
  • Clinical response can be sluggish– fevers regularly persist for 3-4 days and can last even up to 7-10 days.
  • Tons of prior posts on lung abscesses that are searchable on the blog!

Who should get a D-dimer to “rule out” venous thromboembolism (VTE)?

  • The Choosing Wisely campaign has promoted D-dimer as an alternative to reflexive imaging in appropriate patients.
    • See a nifty video here that demonstrates how to explain this to patients!
  • Recall three important features of D-dimer in the evaluation of VTE:
    • 1) Only validated in the outpatient or ED setting, so it is not an appropriate test in the inpatient setting.
    • 2) Only appropriate to use in LOW RISK patients as calculated by Well’s criteria in whom you hope to rule OUT VTE
    • 3) Age-adjusted D-dimer (if age >50, then D-dimer cutoff=age x 10) correctly identifies patients with VTE as compared to the traditional cutoff (D-dimer=500)

False positive PEs: general versus chest radiology

  • Goop told us about a great study that confirms what many have experienced first-hand: diagnosing PE on CT is difficult, even for radiologists.
  • An American Journal of Radiology Study retrospectively reviewed all CTPEs reported as positive for PE that were performed over 1 year at a tertiary care hospital.
  • 3 chest radiologists reinterpreted any positive study.
  • There was discordance between the chest radiologists and the original radiologist in 45 of 174 (25.9%) cases (e.g. original radiologists reported a study as positive for PE, while all 3 chest radiologists reported it as negative).
  • Discordance occurred more often where the original reported PE was solitary (46.2% of reported solitary PEs were considered negative on retrospective review) and located in a segmental or subsegmental pulmonary artery (26.8% of segmental and 59.4% of subsegmental PE diagnoses were considered negative on retrospective review). The most common cause of diagnostic difficulty was breathing motion artifact, followed by beam-hardening artifact.
  • Thus, takeaway is that PEs are frequently over diagnosed, and it is good practice to review with a chest radiologist, especially if any of the above features are present.