All posts by cauriemma

Moffitt Pulmonary Report Pearls 8.14.17

Thank you to Luis for presenting a case of an elderly woman with history of bronchiectasis and MAC presenting with fevers, cough and chest pain. We were joined by Bhavika Kaul from pulmonary!

Key Pearls

  1. Ditty pearl: Use ABCD2 score (age > 60, BP >140, clinical features, duration > 60 min & DM) to decide whom to admit after TIA. For a score > 2 hospitalization recommended given higher risk (> 4 %) of 2 day CVA.
  2. Faget sign (sphygmothermic dissociation) is described as a temperature-pulse dissociation and is often a sign intracellular organisms with typhoid fever being a common boards question. MOST common cause of fever, HR dissociation… beta-blockade.
  3. Diagnosis of MAC requires BOTH microbiology and the appropriate clinical context (more details below).

Diagnosis of MAC in the Non-HIV Patient

  • Microbiology
    1. Induced sputum with at least 2 positive cultures  Or
    2. At least 1 bronchial lavage Or
    3. Transbronchial biopsy with mycobacterium
  1. Clinical Context:
    1. Pulmonary symptoms, nodular or cavitary opacities on CXR or CT scan with multiple nodules and bronchiectasis   AND
    2. Exclusion of other diagnoses

Treatment of MAC

  • Remember that macrolides are the cornerstone of therapy and you DO NOT want to use Azithromycin as a single agent given risk for resistance and partial treatment.
    • Hence, avoid azithro as single drug coverage or part of treatment for superimposed CAP in patient with possible MAC
  • For most patients being treated for MAC pulmonary disease require a three-drug combination regimen
    • Selection depends, in part, on susceptibility to macrolides; most MAC isolates are macrolide susceptible.
    • Antimycobacterial treatment is difficult to tolerate (weight benefits & risks) & continued until sputum cultures are consecutively negative for at least 12 months. 

Fun Fact!

50% of patients with advanced HIV patient (CD4 <50) with a positive sputum culture for MAC who are NOT TAKING MAC ppx will get disseminated infection (fevers, weight loss, rising LFTs and cytopenias).


 Differential Diagnosis for Bronchiectasis

  • Chronic infections
  • Chronic aspiration
  • History of childhood infections
  • Cystic fibrosis
  • Cigarette smoking
  • Inflammatory – Rheumatoid Arthritis and Sjogren’s Syndrome
  • Allergic bronchopulmonary aspergillosis (ABPA)
  • Ciliary dyskinesia

Evernote: https://www.evernote.com/shard/s462/sh/52c9c737-6173-4108-8804-5652964366f4/7bc8596565dd78a597987d8d5f322ff4

Morning Report 8/9/17 – GI report!

Thank you, Luis, for presenting two cases this morning!! The first was a middle-aged male with AF and HFrEF 2/2 recent STEMI s/p stenting on triple therapy presenting with lightheadedness found to a Hgb of 4.7. We had a lively discussion on management of anticoagulation in a possibly bleeding patient s/p STEMI.

The second case was quick image of a patient with possible SMA syndrome!

Key Pearls

  • Triple therapy (systemic anticoagulation + DAPT) may be overkill for most patients. The WOEST trial is our best evidence to support trimming down (see below for a deep dive into the trial).
  • Isolated gastric varices may suggest splenic vein thrombosis. If confirmed, you’re obligated to evaluate for hypercoagulability – often from a myeloproliferative disorder.
  • Use the Dual antiplatelet score (DAPT Score) to help decide when to discontinue an antiplatelet therapy. This is not validated post-MI, however.

 


WOEST trial

 

Patients on systemic anticoagulation with warfarin were randomly assigned to receive either clopidogrel alone or clopidogrel + aspirin immediately following PCI. This trial included all-comers undergoing PCI.  Approximately 1/3 of the patients in both arms of the study had myocardial infarctions preceding their PCI. The number of patients excluded from the trial was pretty minimal, but interestingly the criteria would have excluded the patient we discussed today (WOEST exclusion criteria:  h/o ICH, cardiogenic shock, contraindication to anti-platelet therapy, PUD in the last 6 months, thrombocytopenia, major bleeding). The primary outcome of the study was any occurrence of bleeding during 1-year follow-up. The secondary endpoint was a composite of death, MI, stroke, target-vessel revascularization, and stent thrombosis.

 

At 1 year, 19.4% of the patients on double-therapy compared to 44.4% of the patients on triple therapy had experienced a bleeding event. This translates to a hazard ratio of 0.26 (95% CI 0.26-0.50).


There was no statistically significant difference in the rate of thrombotic events between groups. HOWEVER, it’s important to remember that this study was not powered to detect a difference in the occurrence of thrombotic events.

Why does that matter?  Because the overall rate of stent thrombosis is SIGNIFICANTLY lower than the overall rate of bleeding, a much larger trial would be needed to detect differences in stent thrombosis. To put some numbers on this, when powering their trial, the WOEST authors estimated that the rates of bleeding would be 12% in the triple therapy arm and 5% in the double therapy arm. Compare that to an expected rate of early stent thrombosis of 1% in the first 30 days and 0.2-0.6% per year after that.

So if the rate of stent thrombosis is so low, why are we all so afraid of it? Because the mortality and morbidity are crazy high! – acute stent thrombosis has been associated with mortality rates of 20%–45% and myocardial infarction rates of 50%–70%. Furthermore, approximately 20% of patients who have stent thrombosis will have a recurrent episode within 2 years.

Therefore, based on the WOEST trial, we can surmise that double therapy (warfarin + clopidogrel) has LESS BLEEDING than triple therapy (double + ASA), but we can’t say for sure whether there is a difference in thrombotic risk.

Dewilde WJ, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013 Mar 30;381(9872):1107-15. doi: 10.1016/S0140-6736(12)62177-1. Epub 2013 Feb 13.
Reejhsinghani R, Lotfi AS. Prevention of stent thrombosis: challenges and solutions. Vascular Health and Risk Management. 2015;11:93-106. doi:10.2147/VHRM.S43357.

What is DAPT Score??

https://www.qxmd.com/calculate/calculator_373/dapt-score

 

Created to predict combined ischemic and bleeding risk for patients being considered for continued thienopyridine therapy (clopidogrel) in addition to aspirin beyond 1 year after coronary stent treatment. 

 

The score was developed from the DAPT Study randomized trial data, in which patients were randomized to continued thienopyridine therapy (clopidogrel or prasugrel) vs. placebo. Patients were randomized only if they had NOT sustained a MI, stent thrombosis, stroke, repeat revascularization, or bleed, and had been adherent with medications during the first year. Patients receiving oral anticoagulation or with limited life expectancy were excluded. 

 

When DAPT score is ≥2, the number needed to treat (NNT) to prevent an ischemic event was 33 and the number needed to harm (NNH) with a bleeding event was 263. 


 

Evernote:  https://www.evernote.com/shard/s462/sh/a32c1c33-eceb-41b9-963c-b944771d4868/e50b54fdf4cd9f2189141f938a5fdb86

 

 

Morning Report Pearls – 8/7/17

Thank you, Vaibhav, for presenting an unfortunate case of a young woman with HLH managed with etoposide and steroids who developed monoarticular vision loss found to have angioinvasive mucor.

Key Pearls:

  1. The name HLH, hemophagocytic lymphohistiocytosis, helps to describe the pathology seen in the disorder – an over-activation of histiocytes leading to unbridled hemophagocytosis.
  2. The differential diagnosis for the orbital apex syndrome is a fascinating one including infectious etiologies, non-infectious inflammatory conditions, infiltrative disease, and malignancies.


Hemophagocytic lymphohistiocytosis – a condition of excessive inflammation and tissue destruction often, in adults, in response to an infection, additional autoimmune disease, or malignancy (secondary HLH). The tissue destruction is due to excessive macrophage activity .

Diagnosis made by meeting 5 of 8 criteria:

  1. Fever > 38.5
  2. Splenomegaly
  3. Ferritin > 500 (but usually in the thousands)
  4. Cytopenias: at least two of Hgb <9, platelets <100K, ANC <1000
  5. Hypertriglyceridemia and/or hypofibrinogenemia
  6. Absent or decreased NK cell activity
  7. Elevated soluble IL-2 receptor (CD25)
  8. Biopsy-proven evidence of hemophagocytosis in bone marrow, spleen, lymph node, or liver

 


Orbital Apex Syndrome – opthalmoplegia + progressive vision loss, often with proptosis

DDx:

  • Infectious: bacterial extension, invasive molds, TB
  • Malignant: NK/Tcell lymphoma
  • Inflammatory or Infiltrative: sarcoid, GPA, orbital pseudotumor (lymphocyte infiltration), sinus histiocytosis with massive lymphadenopathy
  • Other: cocaine-induced midline destruction

Evernote: https://www.evernote.com/shard/s462/sh/53206afb-70bb-4ff5-a325-b5a85143e4b6/3428a764c475f55b73941b621fddab79

 

Morning Report Pearls – 8/4/17

Thank you, Gabby, for presenting the case of an older man with an upper lobe lung mass and rapidly declining kidney function who was found to have GPA plus a single positive AFB smear. We discussed the risks and benefits of starting immunosuppression + RIPE.

Key Pearls:

  1. Harry’s rule of thumb for the common renal manifestations of tuberculosis: 1/3 with sterile pyuria, 1/3 with hematuria, and 1/3 with a mixture of both!
  2. Repeating the MTB PCR test increases your sensitivity for picking up smear-negative, culture-positive TB from <60% with 1 PCR to 70% with 2.

Renal Disease in Tuberculosis

  • Present in up to 20% of patients with extrapulmonary TB 
  • 90% of patients with genitourinary TB will have pyuria and/or microscopic hematuria 
  • Heavy proteinuria, cellular casts, and elevated plasma creatinine are all unusual

Here is a very cool clip from the Images in Clinical Medicine series from the NEJM. The patient presented had a notable LUL pulmonary cavitary lesion and a densely calcified, atrophic left kidney. He was ultimately diagnosed with a left autonephrectomy secondary to TB!


Sensitivity of MTB PCR (Gene Xpert)

Evaluated and described in detail by Anne Luetkemeyer et al. A summary of the improvement in sensitivity using MTB PCR compared to AFB alone is presented below.

Evernote: https://www.evernote.com/shard/s462/sh/e28ab106-f33b-4d96-ad76-a7d1bbf06a8a/5b3845e61b8569c91631954f54bac9a4

 

Moffitt Morning Report Pearls 8/2/17

Thank you to Tim for presenting a VERY exciting case of a woman who developed hemopericardium with tamponade physiology requiring an emergent bedside pericardiocentesis!
Key Pearls:
1.  Remember tamponade as a cause of obstructive shock.  Beck’s triad is a hint,  but is NOT always seen. In fact, the classic findings are only seen in 10-40% of tamponade cases.
2.  There are key features of ECG and ultrasound that can suggest tamponade, but the diagnosis is ultimately a clinical one.

Cardiac Tamponade

 
Physical Exam
Beck’s triad:
  1. Muffled heart sounds
  2. Jugular venous distension
  3. Hypotension
Only seen in 10-40% of tamponade cases (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1995065/)
Pulsus paradoxus is another key physical exam finding.
ECG findings
  • Electrical alternans
  • Low voltages – suggest possible effusion, not necessarily tamponade
US/ECHO findings
Key features to look for on bedside ultrasound or echocardiography are:

  • presence of an effusion (duh! – though sometimes a pericardial fat pad can fake you out)
  • Early diastolic collapse of the right ventricle:
  • Late diastolic collapse of the right atrium:
  • Dilated IVC with no respiratory variation:

Check out this article by Goodman et al. discussing the use of bedside cardiac ultrasound in the diagnosis of pericardial effusion and tamponade physiology, and the source of the images above.

Moffitt Morning Report – 7/31/17 – CCB/BB toxicity

Thank you, Tim, for presenting the case of a middle-aged man with CAD presenting with ankle pain and chest pain, admitted for high risk chest pain, noted to have acute onset of hypotension, bradycardia, hypoxemia, and decreased mental status in the setting of receiving multiple antihypertensive medications.

 

Key Pearls:

  1. 6 Ps of ischemia: pain, pallor, parasthesias, poikilothermia, pulselessness, paralysis.
  2. Over 75% of patients with peripheral arterial disease have significant coronary artery disease, hence why presence of PAD is considered a risk factor equivalent for CAD.
  3. Hyperkalemia is a cause of bradycardia, especially when combined with AV nodal blockade! See BRASH syndrome below.

 

BRASH syndrome is defined as a combination of the following:

  • Bradycardia
  • Renal injury
  • AV node blocker: beta-blocker, verapamil, or diltiazem (2)
  • Shock
  • Hyperkalemia 
Here’s a great EM Crit post on this syndrome that discusses the mechanisms involved in how the combination of AKI + AV nodal blockade can worsen hyperkalemia.

In this article outlining the management of CCB and BB overdose, the authors present a summary of the pharmacologic agents used in the treatment of shock from CCB and BB poisoning.

 

Evernote: https://www.evernote.com/shard/s462/sh/d2d699ac-f33a-4b36-bcb8-8cadc9a8e7e4/d6da124a0882a695b9cff5bfec3334de

Moffitt Morning Report – 7/28/17 – Pancytopenia

Thank you, Kate, for presenting a case of a young, previously healthy who was transferred to Moffitt with pancytopenia, elevated LFTs, and splenomegaly.

Key Pearls:

  1. Marrow aplasia + hepatocellular injury should prompt you to think about acute viral hepatitis (A, B, C), HIV, and HSV.
  2. Think of the bone marrow as a garden – you can have a garden with no flowers, sick flowers, or totally overrun with weeds.
  3. CMV serologies are not particularly helpful in working up acute infection. The PCR is much more helpful. Serologies are relevant in transplant patients to know their risk for reactivation.
  4. If you’re interested in an Occupational Health consult – email Paul Blanc from the VA!


 Quick reminder re: The classic initial approach to any cytopenia:

  • Underproduction
  • Increased destruction
  • Sequestration

 The reticulocyte count is a great way to help differentiate a functioning from malfunctioning marrow!


Approach to pancytopenia due to decreased production:

  • Hypocellular: The garden has no flowers
  • Normocellular, but abnormal: The garden has flowers, but they’re not doing so well
  • Infiltrative process: The garden is overrun with weeds

A bone marrow biopsy should be obtained relatively early in the work-up of aplastic anemia and will further guide the differential diagnosis.


As we learned from HH, there are really only 4 results one can get from a bone marrow biopsy:

  1. aplastic/hypoplastic
    1. Immune destruction/suppression – aplastic anemia, PNH
    2. Infection: EBV, CMV, hepatitis, Brucella
    3. Toxins: Meds, Exposures (Benzine is a classic example)
    4. Nutritional: B12 deficiency, folate, excess alcohol
  2. infiltrated – malignant or nonmalignant causes
    1. granulomatous – fungal, tuberculous
    2. MDS, leukemia, myeloma, metastatic cancer
  3. fibrotic
  4. serous atrophy (usually severe nutritional deficiency)

For an overview of the diagnosis and treatment of APLASTIC ANEMIA, check out this recent review.

Mini summary of treatment options:

  • Standard treatment for young (<50-60), fit patients is a matched HSCT – will provide a cure in about 90% of patients!
  • For older patients or those without a matched SCT donor, combined immunosuppression is the next best option.

Congenital Causes of Aplastic Anemia:

Diamond-Blackfan, Fanconi – generally present MUCH earlier – even as early as in infants


Summary of PNH with a reminder of the work-up:

  • Caused by a somatic mutation in the bone marrow stem cells. Generally presents as a hemolytic anemia with intermittent fatigue, abdominal pain, jaundice and pink/red urine.
  • One of the conditions associated with both arterial and venous clots!
  • Flow cytometry with >10% of cell population missing the CD 55 and CD 59 markers. These result in inappropriate inactivation of the complement cascade and cellular destruction.

Reminder of the mechanism of hemolysis in PNH:

 

Image from: http://www.netflowconnect.com/what-is-pnh/pathophysiology/