Day #264 Sickle Cell Anemia

Today we discussed a patient with sickle cell anemia (previous blogs) who presented with acute onset chest pain, bilateral chest xray infiltrates and profound hypoxemia.

This patient had a compound heterozygote of sickle and beta-thalassemia. A review of the various compound heterozygotes is available here.

This patient may have had chest crisis. We did not see the initial xray. The definition of acute chest crisis/syndrome:

• New Chest Xray Infiltrate with chest pain
  AND


• One of: cough, fever, hypoxemia, tachypnea, sputum

A review of the ACS is available here. A more detailed review of the pulmonary complications in sickle cell anemia is available here.

We discussed red cell exchange (review here) which should be considered in ACS.

---

The patient also complained of crushing retrosternal chest pain with a new left bundle branch block on the ECG. This turned out *not* to be myocardial ischemia; although this was diagnosed retrospectively. Interpreting STEMI in the context of LBBB is difficult. This article discusses the relationship of bundle branch block to MI and suggests means of diagnosis that are relatively specific but not sensitive.

A further meta-analysis is available here.

Clearly we need to do better at picking up ischemia in the context of LBBB. I suggested that a STAT echo may have been helpful in this case in picking up LV dysfunction which would be expected with an ischemic LBBB. This is in keeping with the recomendations of the American college of cardiology.

Day #263 - Hemoptysis

Today we discussed a patient with previously resected lung cancer who presents with new onset worsening of hemoptysis. We've previously discussed haemoptysis here .

This case subsequently turned out to be a pulmonary hemmorhage syndrome (Churg Strauss) with glomerulonephritis. There is a good case report in the NEJM here. There is another case in NEJM here as well.

The original case description is available here.

A review on pulmonary vasculitis here.

Day #259 - Hepatic Encephalopathy

Today we heard about a case of a man who presented with acute hepatic encephalopathy of multiple possible etiologies including substance withdrawal and probable GI bleeding.

We reviewed the complications of nasogastric tube insertion.

I have blogged extensively on cirrhosis and its complications (and treatment thereof) previously (here, here, here, and here)

Previous blogs on upper GI bleed here and here.

Day #258 - Meningovascular Syphilis

Today we heard a case of a young man with headache and diplopia who rapidly went on to develop ischemic brain lesions and progressive deficits.

I have blogged about diplopia here.

The final diagnosis was meningovascular syphilis. The discussant also described the natural history (or stages) of syphilis as I have covered here.

Day #257 - Viral Encephalitis

Today we heard the story of a young woman with fever, headache, photophobia, and confusion/drowsiness with a normal CT and an LP with a lymphocytic pleocytosis with elevated protein. The presumed diagnosis was viral meningoencephalitis and she was treated with IV acyclovir.

Despite excellent data on bioavailability, there are only case reports of substituting oral valacyclovir for IV acyclovir in the treatment of HSV encephalitis. This would be an interesting option which would decrease the need for IV in patients who recovered after IV "induction". It is biologically plausible because the levels in the plasma achieved by valacyclovir approximate acyclovir without the concomittant nephrotoxicity. Apparently clinical trials are underway.

We have previously blogged about HSV encephalitis here.

Day #256 -Pleural Effusion/Congestive Heart Failure

I have previously blogged about the approach to pleural effusion here.

We reviewed some general causes of:

Exudate:

• Malignancy
• Infection
  
  • Parapneumonic
  • Empyema
  • TB
  • Subdiaphragmatic abscess
    
• Inflammatory
  
  • SLE/RA/FMF
• Pulmonary Embolism
  
• Hemothorax/Chylothorax

Transudates:

• CHF
• Cirrhosis (including sympathetic)
  
• Nephrotic Syndrome
• Malnutrition
• Hypothyroidism

I have previously discussed congestive heart failure here (link to guidelines there as well).

A summary of the class I recommendations:

• Moderate salt restriction in the diet with daily weights
• Exercise testing and exercise programme
• Stop offending medications (i.e. NSAIDS, most calcium channel blockers)

• Diuretics (e.g. furosemide) as required to keep euvolemic
• ACE inhibitor such as lisinopril, enalapril, ramipril, etc. as tolerated. ARB in patients who are intolerant of ACEi due to cough
  
• Beta-blockade with beta-blocker proven to influence outcome in CHF. Start slowly, when euvolemic, with very slow titration in advanced HF (e.g. carvedilol, bisoprolol)
• Consider adding digoxin (see dosing here) to improve symptoms and decrease hospitalization.
• Consider adding spironolactone in patients with NYHA III/IV symptoms and LVEF less than 35% to ACEi or ARB if Cr less than 150 and K+ less than 5 and you can monitor potassium and renal function. Caveat publication here.
  

Assessment of revascularization and modification of the cardiac risk factors is also important.

When he is no longer NYHA IV, and he is on MAXIMAL medical therapy, and he is expected to live more than one year, he can be considered for an ICD (Ischemic Cardiomyopathy with EF less than 35%) for primary prophylaxis of arrythmogenic death.

An article discussing LV thrombi in the context of ischemic cardiomyopathy is available here.

Scenario - Pericarditis

Examples of ECGs of the 4 stages of pericarditis are here.

• Stage 1: Diffuse concave ST elevation with PR depression
• Stage 2: PR depression only with pseudonormalization
• Stage 3: T wave inversion
• Stage 4: Normalization

Good review in NEJM here. A further review on the use of colchicine in the treatment of acute and recurrant pericarditis is available here.

Day #253 - Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis:

Older, but still relevant NEJM review.

There are few treatment options aside from lung transplantation, which actually substitutes one chronic disease for another. A review is available here.

We discussed the concept of "acute exacerbation" of IPF -- a review of this condition and the treatment is here. The mortality is approximately 60-70% at 3 months.

Like many diseases, exercise programs can be helpful in improving functional status.

Day #252 - Infective Endocarditis (Staphylococcus Aureus)

Today we heard a case of a patient with a known history of injection drug use who presented with multiple swollen joints, in the context of a persistant staphylococcal bacteremia. The patient also had a history of previous endocarditis and on exam had evidence of moderate-severe tricuspid regurgitation.

I have reviewed the diagnostic criteria for endocarditis here.

I have previously blogged about staphyloccocal bacteremia here. I will re-iterate that for methicillin sensitive staph aureus vancomycin is INFERIOR to beta-lactam therapy.

Some newer evidence suggests that the risk of using adjuvant gentamicin in native valve staphylococcal bacteremia/endocarditis is greater than the benefit.

An interesting concept, which I am now going to endorse because it is inexpensive and relatively simple, is continuous cloxacillin infusion as opposed to intermittant infusion. In this study the 30 day microbiologic cure was 94% in the CI group as opposed to 79% in the II group (ARR 15%, NNT 8).

There have been several studies looking at treatment options in injection drug users. Long term antibiotic therapy requires indwelling lines and this usually mandates extended hospitalization or "confinement" if ongoing drug use is a concern. These two studies (larger study, smaller study) have evaluated quinolone (ciprofloxacin, though today levofloxacin or moxifloxacin would likely be even more effective) combined with rifampin in right sided IE. These are small studies, so they shouldn't influence practice in general -- but in certain cases may be the only option.

Day #251 - DVT (Phlegmasia Cerulea Dolens)

Today we heard a case of a patient who presented with an acute, cold/blue, painful leg. The cause of this was identified as a mixture of a large DVT on a background of peripheral vascular disease.

In phledmasia cerulea dolens (see right, from NEJM) the DVT, usually very large, causes venous outflow obstruction which, in turn, leads to elevated tissue pressures which can significantly reduce arterial flow leading to tissue ischemia.

In today's patient they presented with a lactic acidosis probably related to tissue hypoxemia.

There are a number of interesting articles about interventional and surgical approaches to the treatment of massive DVT causing PCD. The goal of therapy is to salvage the limb before it becomes gangrenous. This article discusses manual clot aspiration. This is a more complete review of the interventional options.

Note: in our case, thrombolysis was contraindicated because of the recent large ischemic stroke.

My colleague at TWH has posted a summary of the "Wells Criteria" for the clinical diagnosis of DVT.

Using this algorithm, a low risk patient with a negative D-dimer does not have a DVT. A high risk patient, or one with a positive D-dimer will require further investigation.

Duplex Compression Doppler Ultrasound is usually the test of choice. Treatment involves anticoagulation with heparin (unfractionated or low molecular weight depending on clinical scenario -- usually LMWH) which is generally followed by coumadin after 2 days of anticoagulation with overlap until INR 2-3 x 2 days and a minimum of 5 days of heparin

Day #250 - Safe Patient Signover

Today was a special session on safe signover practices. Signover/Signout/Handover of care between physicians (particularly at teaching hospitals) is one of the most dangerous times. By paying attention to the process, we can improve the quality of signover and hopefully provide safer and more efficient cross-coverage.

The presenters referenced these articles:

• ANTICipate - A model for generating a sign out list
• SIGNOUT? - A model for verbal signover
• "Consequences of Inadequate signout"
  

Day #249 - ITP

Today we heard the case of a patient with severe thrombocytopenia, presumed ITP (bone marrow biopsy pending)

I have previously blogged about thrombocytopenia here.

Day #245 - (Cryptogenic) Organizing Pneumonia

Today we talked about a case of a patient with organizing pneumonia in the context of advanced rheumatoid arthritis on penicillamine.

The discussant reviewed the respiratory complications from RA:

• Pulmonary nodules
• Pleural effusion
• Pulmonary Fibrosis
• Bronchiolitis Obliterans
  
• Organizing pneumonia
• Cavitary disease -- with pneumoconiaosis (Caplan's syndrome)
• Related to immunosuppression (i.e. methotrexate lung)
  

We then discussed the diagnosis and management of organizing pneumonia in rheumatoid arthritis.

Day #244 - Pulmonary Embolism in CML

I have discussed PE/DVT before here (diagnosis, management)

There is a good taxonomy of the myeloproliferative disorders and leukemias here. Another (less detailed but more readable) review is available here.

A specific review of thrombocytosis and its management (which this patient has) is available here.

The NEJM has an article on the initial treatment of CML (which I suspect this patient has).

Day #243 Atrial Fibrillation and Congestive Heart Failure

We've previously discussed atrial fibrillation and the urgent management thereof here.

This patient was on digoxin, and was not toxic. I've discussed digoxin toxicity and the use of digoxin in CHF here.

I have discussed CHF here and some of the causes of cardiomyopathy here. An article on cardiomyopathy taxonomy is available here.

Day #242 - Syncope

The approach to syncope involves an attempt to determine the etiology on the basis of the history, physical exam, and investigations. A guideline is available here.

Approximately 20% of the population, at any age, will have syncope.

• Cardiogenic Cause (Highest 1yr mortality)
  
  • Structural - AS, HOCM, Severe MS, Myxoma, Other
  • Arrythmogenic -
    
    • Tachyarrythmia: Atrial fibrillation, VT/VF, other
    • Bradyarrythmia: Sinus arrest, "Sick Sinus Syndrome", AV Block
  • Ischemia/Aortic Dissection
  • Tamponade
    
  • Pulmonary Embolism/Pulmonary Hypertension
    
• Neurogenic/Neurocardiogenic Cause
  
  • Vagally mediated - vasovagal, defication, micturition, cough/sneeze
  • Orthostasis/Hypovolemia
    
    • Drug induced (i.e. diuretics/vasodilators)
    • Disease mediated (i.e. autonomic dysfunction from DM, or Parkinson's)
    • Hypovolemia from any cause
      
  • Carotid Sinus Hypersensitivity
  • Choking on a pretzel...
    
• Not Syncope
  
  • Seizure
  • Pseudosyncope

Scenario Rounds -- Status Epilepticus

See here.

Day #239 - Clostridium Difficile (C. Diff)

Today we discussed a case of severe Clostridium difficile associated diarrhea. I have previously blogged about the differential of colitis here.

There is a general review of C. difficile available from last week's JAMA. I prefer these two (#1 and #2) editorials by John Bartlett.

A full suppliment to the journal Clinical Infectious Diseases was devoted to C. difficile in January 2008 and it is very good.

Diagnosis of C. Diff

Microbiology

• At our hospital, the C. diff toxin assay (EIA) detects toxins A and B and has ~70% sensitivityon a single test, with ~90-95% sensitivity on three tests. The specificity greater than 95%.
• The most sensitive assay is the test for cytopathic effect, which is not available
• You can also culture Clostridium difficile from the stool, although most laboratories no longer do this, and just because you grow it does not necessarily mean that it is causing disease

CT Scan

• May show thickening of the bowel wall, colitis, ileus. "Double Halo" and "Accordian Signs"
  

Sigmoid/Colonoscopy

• May see pseudomembranes diagnostic of pseudomembranous colitis

Treatment of First Episode

• If possible stop offending antibiotics
• Mild/Moderate Disease
  
  • Metronidazole OR Vancomycin (PO) duration 10-14d
    
• Severe Disease
  
  • Defined as:
    
    • Two of (Age above 60, Febrile, WBC above 15, Albumin below 25)
      
    • OR hypotension/shock or Cr greater than 1.5x normal, or toxic megacolon, peritoneal signs, perforated bowel
      
  • Infectious Disease +/- General Surgery Consultation
  • ICU Consult for patients with hemodynamic comprimise
    
  • Vancomycin (PO) unless severe illeus, then Metronidazole (IV) duration 10-14d
    

Relapse

• First relapse --> can repeat last treatment depending on severity
• Second relapse --> vancomycin taper (see JAMA article). ID consult.
  

Day #238 - Cirrhosis and Pancytopenia

Today we discussed a case of presumed cirrhosis and pancytopenia from chronic ETOH over-use.

I have previously blogged about cirrhosis (including management of complications, approach to ascites/SBP) here and here.

The Physical Exam for ascites is reviewed here. How-to paracentesis here.

I have also blogged about the approach to macrocytic anemia here.

Day #237 - Hepatoma and HCC

Hepatocellular carcinoma is a highly vascular primary cancer of the liver which often arises in the context of underlying cirrhosis and ongoing/chronic liver inflammation caused by viral hepatitis (B and C). In general the risk in cirrhosis is approximately 3% per year.



The diagnosis is often made based on the radiographic appearance and clinical context. From uptodate: "If the lesion is hypervascular, has increased T2 signal intensity, demonstrates venous invasion, or is associated with an elevated AFP, the diagnosis is almost certainly HCC."

There are several staging systems. One useful system is the CLIP score:

• Underlying liver disease:
  
  • Child-Pugh A = 0, B=1, C=2
• Size and extent of tumour
  
  • Uninodular and not extending more than 50% =0
  • Multinodular and not extending more than 50% =1
  • Massive or extending more than 50% = 2
• AFP greater than 400 = 1
• Portal vein thrombus =1

CLIP: 0, 1, 2, 3, 4, 5/6 has associated median survival of 31, 27, 13, 8, and 2 months respectively.

There can be several paraneoplastic syndromes associated with HCC:

• polycythemia (related to EPO)
• hypercalcemia
• hypoglycemia
• chronic watery diarrhea
  

Treatment:

• In general surgical resection is limited to patients with good hepatic reserve (CPA), absence of metastases, absence of invasion of major vascular studies.
  
• Surgery is generally more successful in lesions less than 5cm
• Transplantation of the liver can be an option in patients with inadequate reserve or otherwise unresectable lesions. This really is only an option for lesions less than 3-5cm and solitary or less than three lesions.

• Radiofrequency ablation (RFA) is an option for lesions less than 4-5 centimeters who are otherwise deemed unresectable.
• TACE (transarterial chemoembolization) is an option for unresectable lesions in the absence of portal vein thrombosis. It is relatively contraindicated in tumours making up more than 50% of the liver, heart failure, renal failure, ascites, GI bleeding or thrombocytopenia.
  

There was a recent publication on the use of tyrosine kinase inhibitors in the treatment of advanced HCC showing improved survival.

I have previously blogged about hepatitis B, the most common worldwide cause of hepatoma, here.

Day #236 - Pneumocystis (PCP) x 3

I've previously blogged about PCP here.

We discussed opportunistic infections in HIV here.

A previous talk I've given on HIV is available here.