Tangents

"what about my water pill, doctor?"

2012-01-26T09:21:00.004-05:00

This morning we briefly talked about the mechanism of action of furosemide (lasix). This drug is a loop diuretics that inhibits the Na-K-2Cl channel in the thick ascending limb of the loop of Henle on the luminal side.

The efficacy of Furosemide is dose-dependent, but a plateau is reached in which even higher doses produce no further diuresis (when all the channels are saturated). The bioavailability of furosemide is only about 50%, so IV is twice as potent as oral. The drug is renally cleared.

IV therapy is preferred in patients with decompensated heart failure initially because drug absorption may be slowed by decreased intestinal perfusion and mucosal edema.

Furosemide is a sulfonamide drug so can cause hypersensitivity reactions, but patients with a history of allergy to sulfonamide antibiotics usually tolerate furosemide with little cross-reactivity.

Another side effect furosemide to be aware of is ototoxicity.

Here is a review article on diuretic therapy.

Pleural Effusion and Ultrasound

2012-01-25T12:21:00.003-05:00

At Gel Rounds today, we discussed pleural effusion. The image above is the ultrasound image of a small right sided effusion. The top of the image represents the probe resting on the chest wall, the dark area (e) is the effusion. The Bright band between (e) and the liver is the diaphragm (d). The lung is seen superior and deep to the effusion.

Now that you know how to identify pleural effusion with the ultrasound, use it in addition to your physical exam when doing a bedside thoracentesis.

Prothrombin-Complex Concentrates (PCC )

2012-01-12T09:23:00.003-05:00

This morning we discussed the use of PCCs in reversing the INR. PCC is the combinations of vitamin K-dependent coagulation factors (ie, factors II, VII, IX, and X). It is used to normalize the INR and acts more rapidly than FFP or vitamin K alone.

PCC available in Canada is Octaplex (there are more in the market). This is a human blood product derivative (not a recombinant).

Advantage of using PCC is the much lower volume load compared to FFP. Thrombotic complications (such as DIC or MI) have been reported with PCC, but this risk is difficult to quantify.

Vitamin K should be given if you need to completely reveres INR even when using PCC to avoid delayed secondary rise in the INR as the coagulation factors are metabolized (remember factor VII has a half-life of four to six hours in vivo).

The cost of INR reversal with PCC is between $1000-$3000 USD.

Here is a review on reversal of vitamin K agonist therapy.

The Perfect Storm

2012-01-09T09:54:00.003-05:00

This morning we discussed a case of thyroid storm. This is a life-threatening condition, characterized by exaggerated symptoms of hyperthyroidism.

Thyroid storm can present as first time presentation of thyroid disease, but more commonly seen in those with long standing history of hyperthyroidism triggered by infection, trauma, surgery, post-partum, or an iodine load.

Patients are often tachycardic with hemodynamic instability, and can have hyperpyrexia, altered LOC, and GI symptoms. Given the high mortality associated with thyroid storm (20-30%), a high index of suspicion should be kept in patients with history of thyroid disease.

Here is a review on thyroid emergencies.

Happy Holidays

2011-12-22T15:35:00.002-05:00

On Monday in dermatology morning report we discussed SJS/TEN.

Here is a great reference that our presenter, Dr. A.D., has recommended.

Happy Holidays everyone and see you in January!

Drug-induced liver injury (DILI)

2011-12-20T11:12:00.004-05:00

This morning we discussed drug-induced liver injury (DILI). Many drugs, both prescription and over-the-counter, can cause hepatotoxicity, so a careful medication history should always be obtained when a patient presents with liver enzyme abnormalities.

DILI can range from asymptomatic mild enzyme elevations to fulminate liver failure. Jaundice in addition to elevated enzymes is associated with a worse prognosis than that seen in the setting of isolated ezyme abnormalities (an observation known as "Hy's law").

The most important treatment for DILI is cessation of the offending drug.

Here is a review on DILI.

* H& E stain, liver biopsy, atorvastatin-induced acute hepatitis, Inflammatory cell infilteration of the liver parenchyma consistant with inflammation.

Hypersensitivity Pneumonitis

2011-12-15T09:56:00.005-05:00

This morning we talked about hypersensitivity pneumonitis- also referred to as extrinsic allergic alveolitis.

This condition is an immunologic reaction of lung parenchyma to an inhaled agent, particularly an organic antigen. HP has been identified in various groups including farmers, bird handlers, carpenters, and those exposed to various industrial dusts. Mold exposure in poor housing can cause HP.

HP can present acutely with abrupt onset of fever, cough, dyspnea, and diffuse fine crackles. CXR may be normal or show transient patchy opacities. Subacute HP presents with gradual development of productive cough, dyspnea, fatigue, anorexia, and weight loss. Respiratory symptoms are more severe than with acute HP, and radiographic findings more extensive.

Removal from exposure to the inciting antigen leads to improvement in symptoms.

* Many adults and children suffer from chronic cough and respiratory symptoms secondary to mold exposure in poor housing in the Northern Ontario Cree community of Attawapiskat.

Here is the CBC photo gallery of the Attawapiskat Housing Crisit.

"once a chief, always a chief...."

2011-12-14T09:44:00.002-05:00

This morning, we reviewed a case of HTLV-1 associated T-Cell lymphoma. The human T-lymphotropic virus (HTLV-I) is a retrovirus.

As we discussed, HTLV-1 is also associated with myelopathy, AKA tropical spastic paraparesis (TSP) which causes progressive weakness and spasticity of one or both legs with hyperreflexia.

HTLV-I is diagnosed by serum serology.

Treatment is not indicated for asymptomatic HTLV-1 infection.

*The title of this post has nothing to do with HTLV-1. I just liked Dr. HPK's quote from this morning!

Alcoholic hepatitis

2011-12-13T08:44:00.004-05:00

This morning we reviewed a case of Alcoholic hepatitis at morning report.

Updated Post written by Dr. Wong

Alcoholic hepatitis takes place DURING significant alcohol use. They rarely seek medical attention because the hepatitis is mild and resolves on stopping alcohol for a few days. When they do present to ER, it is usually because symptoms persist despite abstinence. Patients rarely recognize jaundice, but in retrospect will have noticed dark urine.

Alcoholic liver disease can be recognized by the findings of AST > ALT, high GGT and high MCV.

Alcoholic hepatitis presents with AST 80-300 > ALT, low grade fever, a rise in WBC/left shift from baseline (baseline may be low), RUQ tenderness. Mild cases (normal INR) have an excellent survival prognosis. Severe hepatitis (INR > 1.9, Bilirubin > 100 or MELD > 21) has a high mortality risk and steroid therapy should be considered.

Therapy is Prednisone 40 mg OD x 4 weeks, no taper. Therapy is contra-indicated in the setting of infection, GI bleeding or renal failure.

Reassess after 1 week, stop if no improvement in bilirubin.

Nutrition with adequate calories is the other mainstay of therapy.

* Coloured light micrograph of a section through the liver of a patient with alcoholic hepatitis, inflammation of the liver due to heavy alcohol consumption. The normally regular cellular structure of the liver has been disrupted here, and large vacuoles of fat (yellow) are seen. The circular structures at centre are bile ducts.

Hypomagnesemia

2011-12-12T11:47:00.004-05:00

This morning we reviewed a case of severe hypomagnesemia .

Patients often present with generalized weakness and non-specific complaints, but VENTRICULAR ARRYTHMIA and neurologic finings such as delirium and coma can also occur.

ETIOLOGY
- GI losses: diarrhea
- Renal losses: renal failure or renal magnesium wasting due to drugs such as diuretics, aminoglycosides, or cisplatin, or rare genetic causes such as Gitleman's disease
- Alcohol: causes renal tubular dysfunction and urinary loss of Mg.
- Decrease PO intake

**Think of Magnesium depletion in refractory hypokalemia or unexplained hypocalcemia.

MANAGEMENT:
Route depends on severity and renal function

If hypomagnesemic-hypokalemic ventricular arrhythmias: give 50 meq of IV magnesium slowly over 8 to 24 hours and repeated as necessary to maintain the plasma magnesium concentration above 0.4 mmol/L or 0.8 meq/L.

Oral replacement is adequate for asymptomatic patient.

Treat the underlying disease.

Hypertensive Emergency

2011-12-08T10:02:00.003-05:00

We discuss the approach to and management of hypertensive emergency.

Here is a previous post on that topic.

Neurosyphilis (in non-HIV patient)

2011-12-07T09:26:00.006-05:00

This morning we discussed a case of rapidly progressive dementia, likely secondary to neurosyphilis.

Neurosyphilis can occur early or late. It may occur with primary, secondary, or tertiary syphilis. Early neurophysilis can present as stroke, meningitis, meningoencephalitis, cranial nerve deficits, hearing loss (otosyphilis), or visual loss (oculosyphilis). Late neurosyphilis occur decades later and can presents as general paresis, dementia with psychosis (rapidly progressive), or tabes dorsalis (posterior column involvement, bowel, bladder dysfunction).

Syphilis Screen:
CMIA-Chemiluminescent Microparticle Immunoassay (serum)- T.pallidum (IgG/IgM)
VDRL-Venereal Disease Research Laboratory-no longer done at UHN labs.
RPR - Rapid Plasma Reagin Test. Detects total IgG/IgM antibody to syphilis (T. pallidum). Automatically done by lab if CMIA is reactive.

CMIA and PRP are called “syphilis screen” in EPR

Confirmatory Tests:
TP.PA- Treponema pallidum particle agglutination.
FTA.ABS- fluorescent treponemal antibody. Positive confirmatory test(s) are often reactive for life

CSF examination (not done at UHN lab, sent to PHL):
• CSF VDRL is specific but not sensitive
• CSF FTA-ABS is sensitive but not specific

Here is a review of syphilis.

Click here for the Ontario Public Health Lab algorithm for interpreting the MANY permutations and combinations of lab results

* A U.S. Army Educational Commission Poster about Neurosypilis, 1918.

Epidural Abcess

2011-12-06T09:42:00.005-05:00

This morning we discussed a case of fever with back pain and our differential included epidural abscess.

If you're thinking about an epidural abscess, you need to image the spine. MRI is the best modality as it is sensitive to pick early signs of inflammation. CT with IV contrast is an acceptable alternative if MRI is not available. Plain X-ray may show changes of advanced osteomyelitis or discitis but is not used to diagnose an epidural abscess.

Here is a previous post and a reference on Epidural Abscesses.

Once in a while my heart flutters really fast...

2011-12-05T09:59:00.004-05:00

This morning we discussed a case of CHF decompensation secondary to atrial flutter with rapid ventricular response.

Atrial flutter is an arrhythmia of organized atrial activity that is not a sinus rhythm. It can be seen its own or sometime as a transition arrhythmia between sinus rhythm and atrial fibrillation.

Any disorders predisposing to atrial fibrillation can cause atrial flutter including thyrotoxicosis, obesity, the sick sinus syndrome, pericarditis, pulmonary disease, and pulmonary embolism. Mitral valve prolapse and cardiac surgery are also risk factors for developing atrial flutter.

Atrial flutter is very similar to atrial fibrillation its clinical presentation and should be treated the same in terms of rate control and anticoagulation. Ablations therapy is very successful for atrial flutter, however, so long-term antiarrhythmic medications are infrequently used.

Here is review on managment of Atrial Flutter.

* the hallmark of atrial flutter on ECG is the saw-tooth pattern (also referred as a picket fence pattern).

Light's Criteria for Pleural Effusion

2011-12-02T08:54:00.003-05:00

Today at morning report we discussed the Light's Criteria.

Light's criteria for exudative effusion are any of
protein level pleural:serum over 0.5
LDH pleural:serum of over 0.6
pleural LDH over 2/3 upper limit of normal for serum

The combination of the three criteria has a higher sensitivity, but a lower specificity, than each individual criterion. Light's criteria are sensitive for exudate; may have transudates falsely called exudates. If clinical appearance suggests transudate but Light's criteria says exudate, measure albumin in serum vs. pleural fluid. If serum albumin is over 12 greater than pleural fluid almost all have transudative.

Our case had a bloody effusion, which narrows Ddx somewhat to cancer, PE, trauma, infection (inc. pneumonia, TB)

Here is a review of Pleural Effusion by Dr. Light himself!

*A large left sided pleural effusion as seen on an upright chest X-ray.

Ascites

2011-12-02T07:36:00.004-05:00

At Gel Rounds we discussed ascites.

Some key points:

Most sensitive findings (i.e. make it unlikely if not present):
1) flank dullness
2) bulging flanks
3) shifting dullness
4) peripheral edema
-history of increased girth, weight gain, ankle swelling

Most specific findings (i.e. make it likely if present)
1) fluid wave
2) shifting dullness

An approach to the examination in liver disease (besides examining the liver itself)

1) Signs of decompensated liver disease
-jaundice, scleral icterus, dark urine (high bilirubin)
-petechiae, ecchymoses (coagulopathy)
-edema (hypoalbuminemia)
-asterixis, level of consciousness (encephalopathy)

2) Signs of portal hypertension
-ascites
-splenomegaly
-dilated abdominal veins (extreme of this is caput medusae)
-hemorrhoids

Reference:

Click here for JAMA rational clinical exam on ascites.

* using the ultrasound, we looked at the Pouch of Morrison, which is a potential space between the liver and the right kidney. This is the first spot to check if you suspect a small amount of ascites. The picture shows Morison's pouch with fluid present (red arrows).

Pericarditis

2011-10-26T10:10:00.003-04:00

At physical exam rounds today, we reviewed Pericarditis.

Clinical presentation: usually a sudden onset of retrosternal chest pain with a pleuritic component to it, often relieved by sitting up. You may hear a pericardial rub - this is classically described as a triphasic high-pitched sound. The 'tri' refers to 1. atrial systole, 2. ventricular systole, and 3. ventricular diastole.

ECG: may show diffuse, concave ST elevations that do not fit any particular vascular territory. PR depression is also seen.

Treatment: In most cases of idiopathic pericarditis, high dose NSAIDS are effective. Steroids and colchicine also may have a role.

Here is a review article on the topic.

Rhabdomolysis

2011-10-25T15:14:00.002-04:00

This morning we discussed a case of rhabdomyolysis.

Here is a previous blog post on the topic.

*myoglobinuria

Miller Fisher Syndrome

2011-10-24T09:32:00.005-04:00

Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy characterized classically by ascending weakness and absent reflexes. GBS is a heterogeneous disease with several variants. Miller Fisher Syndrome (MFS) is a variant that presents with opthalmoplegia, ataxia and areflexia.

In patients with GBS, CSF has elevated protein and normal WBC. In about 85% of patients with MFS antibodies against GQ1b (a ganglioside component of nerve) is positive, though this testing is not routinely performed.

Here is review of Guillain-Barre Syndrome.

* Dr. C. Miller Fisher, Canadian neurologist who first described the MFS variant of GBS in 1956. He was a stroke neurologist who contributed greatly to our understanding of lacunar stroke, and strokes related to atrial fibrillation.

SSRI and SIADH

2011-10-20T11:22:00.004-04:00

This morning we talked about the association between SSRIs and SIADH.

The article we talked about was a review, by Dr. Liu, of case reports involving various SSRIs and hyponatremia. This study found that the majority (83%) of patients with this complication were over the age of 65. The average time to onset of hyponatremia was 13 days (range 3 to 120 days). This finding has since been confirmed through a prospective study.

Take home message is that elderly patients are at increased risk of hyponatremia associated with SSRIs.

Here is the abstract for the above article.

Here is a great review article about SAIDH.

Mitral Regurgitation

2011-10-20T10:43:00.003-04:00

In physical exam rounds yesterday, we examined a patient with mitral regurgitations.
Here is a previous post on Mitral Regurgitation.

*Doppler ultrasound of the heart showing mitral regurgitation: there is abnormal leakage of blood backward (blue is flow away from the probe) through the mitral valve during systole.

Antimitochondrial antibody

2011-10-18T09:43:00.004-04:00

Antimitochondrial antibody is present in 95% patients with Primary Billiary Cirrhosis. The antibody assay is 95% sensitive and 98% specific for PBC (except if it's done by indirect immunoflorescence).

There has been suggestion that the presence of antimitochondrial antibodies may predict the eventual development of PBC in asymptomatic people based on a small study. About 13% of first-degree relatives of patients with PBC have circulating antimitochondrial antibodies, suggesting they may be susceptible to developing PBC. The clinical significance of this finding remains to be determined.

Here is a great review on Primary Billiary Cirrhosis.

*Immunofluorescent stain shows antimitochondrial antibodies on a liver biopsy specimen.

Endocarditis

2011-10-17T10:06:00.005-04:00

This morning we discussed a case of subacute bacterial endocarditis secondary to Strep viridans.

Here is a previous post on endocarditis with some great review referrences.

* Viridans Streptococcus is a term for a large group of commensal streptococcal bacteria that are either α-hemolytic, producing a green coloration on blood agar plates (hence the name "viridans", from Latin "vĭrĭdis", green), or nonhemolytic.

Hypertension

2011-10-14T09:05:00.004-04:00

This morning we discussed a case of Hypertensive Emergency.

Here is a previous post on this topic.

* William Harvey (1578–1657)the first physician who described the systemic circulation of blood being pumped around the body by the heart in his book "De motu cordis" which became the basis for our current understanding of hypertension.

Hypophosphatemia

2011-10-13T11:01:00.003-04:00

Hypophosphatemia is secondary to decreased intestinal absorption (such as in Vit D deficiency), increased urinary excretion (such as in hyperparathyroidism), or shift into the cells (such as in refeeding syndrome).

Symptomatic hypophosphatemia occur when serum phosphate concentration reaches 0.64 mmol/L. Worrisome symptoms of hypophosphatemia are related to ATP depletion, causing metabolic encephalopathy, impaired myocardial contractility, respiratory failure due to weakness of the diaphragm, a proximal myopathy, Rhabdomyolysis, dysphagia, ileus, and hematologic abnormalities.

Hypophosphatemia should be replaced aggressively even if the patient is not overtly symptomatic, since develop myopathy and weakness.

IV phosphate is potentially dangerous, since it can precipitate with calcium causing hypocalcemia, renal failure due to calcium phosphate precipitation in the kidneys, and possibly fatal arrhythmias. So, if IV therapy is necessary in the patient with severe symptomatic hypophosphatemia, it should be given by slow infusions (over a long period of 4-12hrs).

Paraneoplastic Erythrocytosis

2011-10-12T10:24:00.003-04:00

There are 5 types of tumor commonly associated with the overproduction Epo:

1. Hepatocellular carcinoma: Epo elevation doesn’t always cause erythropoiesis because of RBC production inhibition by malignancy.

2. Renal cell carcinoma: In about 1-5% of patients.

3. Hemangioblastoma

4. Pheochromocytoma

5. Uterine myomata: clue will be absence of anemia in patients with menorrhagia. RBC overproduction is reversed following myomectomy.

*Contrast-enhanced MRI image of a patient with Hb=194, showing renal cell carcinoma(arrow).

HIV and Pneumococcal Disease

2011-10-11T09:45:00.003-04:00

Although we automatically think about opportunistic and atypical infections in immunocompromised patients, it is important to note that , similar to non-HIV infected patients, Streptococcus pneumoniae, is the most common bacterial pathogens of CAP in patients with HIV.

As was discussed this morning, HIV infection substantially increases the risk of invasive pneumococcal infection, particularly among those patients with a low CD4 count <200, and those not on therapy. This increased risk may be partially explained by the observation that HIV infected individuals have a predisposition for pneumococcal nasopharyngeal colonization.

For this reason, the Centers for Disease Control and Prevention (CDC) recommends that all HIV–infected patients be vaccinated (preferably early in the disease while they still have the ability to mount an effective antibody response).

Here is a review on the topic.

Invasive pneumococcal disease in patients infected with HIV: still a threat in the era of highly active antiretroviral therapy. Jordano et al. Clin Infect Dis.38(11):1623.

* Chest radiograph of an HIV positive individual with a CD4 cell count above 200 cells/mm3, revealing right upper lobe consolidation. Sputum and blood cultures were positive for Streptococcus pneumoniae.

Hypercalcemia associated with Malignancy

2011-10-04T09:40:00.003-04:00

We discussed a case of hypercalcemia this morning and reviewed the mechanisms by which malignancy can cause hypercalcemia.

1. Direct metastases to bone: These mets trigger the production of inflammatory cytokines and stimulate ostoclasts. Sometimes osteoclasts are directly stimulated by tumor cells via Osteoclast Activating Factors (eg IL6) in multiple myeloma or lymphoma.

2. PTH related peptide: this is the most common cause of hypercalcemia from non-metastatic solid tumors. Classically in squamous cell lung Ca

3. PTH: this is rare! only a few case reports of PTH being released from tumors

4. Calcitriol: a very common mechanism for hypercalcemia in the lymphomas.

Here is a great review article.
*CT scan of a patient presenting with Ca=3.1, who subsequently was found to hav have small cell lung cancer.

2011-09-29T09:04:00.003-04:00

This morning we talked about a variety of different cases. One of them, involved a patient with a presentation of swollen warm painful knee. Here is a previous morning repot blog post on approach to monoarthritis.

*The Gout by James Gillray. Published May 14th 1799.

Hormone Replacement Therapy

2011-09-26T10:00:00.002-04:00

This morning we briefly talked about the Women’s Health Initiative (WHI)and hormone replacement therapy. WHI was a set clinical trials including two hormone trials in healthy postmenopausal woman 50-70. The hormone trials were stopped early due to increased risk of cardiac events, VTE, stroke and breast cancer. The study did show benefits in reducing fracture and colorectal cancer risk.

Subsequent analysis of the WHI noted that the increased risk of CHD tended to depend on the timing of exposure, with no excess risk observed in younger menopausal women.

Current recommendations are as follows:

Moderate to severe menopausal symptoms can be treated with short term HRT in peri- or postmenopausal women (and no contraindications to estrogen). HRT should be stopped before five years. HRT should not be used as primary or secondary prevention of CAD.

Here is Endocrine Society’s statement on HRT.

Lets SIGN OUT? at TWH!

2011-09-23T09:42:00.003-04:00

Handing over. We do it often. And the information we transfer is critical to patient safety. This morning we talked about SIGN OUT? as a template for our signovers.

S: Is the patient sick? Code status!!!
I: Identifying data
G: General hospital course
N: New events
O: Overall health status right now
U: Upcoming possibilities (if and then statements)
T: Tasks to complete overnight
?: Questions

Every team will function differenly, but sticking to consisten hand over template an style keeps communication flowing, and patients safe.

* it's 5pm...have you Singed Out yet?!

VTE and Malignancy

2011-09-22T11:40:00.002-04:00

The questions of screening for an occult malignancy comes up often when a patient presents with unprovoked VTE. There are multiple observational studies that have confirmed the increased incidence of malignancy among those with VTE, however, none has shown improved survival with aggressive diagnostic testing. None of these studies are prospective.

As a result, the current recommendations is that all patients with idiopathic DVT should be evaluated with careful history. A past history of cancer should be a red flag. Other symptoms such as loss of appetite, weight loss, fatigue, pain, hematochezia, hemoptysis, and hematuria should also raise suspicion about cancer.

A complete physical examination (including digital rectal examination and testing for fecal occult blood, pelvic examination in women), and routine laboratory testing (complete blood count, chemistry panel including electrolytes, calcium, creatinine, and liver function tests), urinalysis and CXR should also be performed. Furthermore, age-appropriate cancer screening (PSA, FOB and C-scope, mammogram) should be offered.

Any abnormality observed on initial testing should then be investigated aggressively.

HCV-associated Cryoglobulinemia

2011-09-21T10:04:00.003-04:00

Cryoglobulins are immunoglobulins that precipitate in cold and dissolve with warming.

HCV infections is associated with Type II or essential mixed cryoglobulinemia (polyclonal IgG and a monoclonal IgM rheumatoid factor directed against the IgG) and Type III or mixed cryoglobulin (polyclonal IgG and rheumatoid factor IgM).

Deposition of antigen-antibody complexes in small and medium-sized arteries leads to the clinical findings of cyroglobulinemia. It is unclear, however, why cryoglobulins are produced and which antigen triggers this process. HCV RNA itself may serve as the inciting agent.

Clinical features include palpable purpura, nonspecific systemic symptoms, arthralgias, lymphadenopathy, hepatosplenomegaly, peripheral neuropathy, and hypocomplementemia (low C4).

Here is a review on the topic.

*image is papable purpura (non-blanching erythematosus papules) found in a patient with chronic HCV infection with mixed cryoglobulinemia.

"Did the green onion make me yellow"?

2011-09-20T09:15:00.004-04:00

Hep A is an RNA virus that spreads by the fecal-oral route. HAV is more prevalent in low socioeconomic areas with lack of adequate sanitation and poor hygienic practices. International travel is the most common risk factor in USA (and Canada).

HAV infection usually results in an acute, self-limited illness and only rarely leads to fulminant hepatic failure in those with underlying liver disease, especially chronic hepatits C infection.

The manifestations also vary with age: HAV is usually silent or subclinical in children. In contrast, infection in adults can vary in severity from a mild flu-like illness to fulminant hepatitis. The incubation period averages 30 days (range 15 to 49 days). Symptoms include fatigue, malaise, nausea, vomiting, anorexia, fever, and right upper quadrant pain followed by dark urine, light stools, jaundice, and pruritus. Lab investigations show marked elevations of serum aminotransferases (usually >1000 IU/dL), bilirubin, and alkaline phosphatase.

Acute HAV infection is diagnosed by the detection IgM anti-HAV in serum.

The treatment is supportive care.

* image: the most widespread hepatitis A outbreak in USA affected 640 people (killing 4) ,in late 2003, was blamed on tainted green onions at a restaurant.

Statin-induced muscle injury

2011-09-19T10:00:00.005-04:00

Muscle injury with statin therapy can range from myalgias to myositis to rhabdomyolysis. Muscle symptoms usually begin within weeks to months after starting statins and usually return to normal over days to weeks after drug discontinuation.

You should warn your patients about new onset muscle pain and weakness when you start a statin. A CK level should be obtained at baseline, but routine monitoring of serum CK levels is not recommended.

Patients with acute or chronic renal failure, liver disease, and hypothyroidism are at higher risk of developing muscle injury. Clinical symptoms or a CK level >10X the upper limit of normal should prompt a drug discontinuation.

Pravastatin and fluvastatin appear to have much less intrinsic muscle toxicity than other statins. After the CK has returned to baseline, patients may be tried on a statin less likely to cause muscle toxicity with careful monitoring.

Here is review on the topic.

An assessment of statin safety by muscle experts. Thompson PD, Clarkson PM, Rosenson RS, National Lipid Association Statin Safety Task Force Muscle Safety Expert Panel. Am J Cardiol. 2006;97(8A):69C.

Antibiotics in COPD exacerbation

2011-08-25T09:50:00.005-04:00

The use of antibiotics in exacerbations of COPD is based on small placebo-controlled trials and large retrospective population studies. They found that antibiotics improve clinical outcomes in severe COPD exacerbations. There is little evident for the use of antibiotics in mild exacerbation.

A recent cochrane review on the topic concluded that "in COPD exacerbations with increased cough and sputum purulence antibiotics, regardless of choice, reduce the risk of short-term mortality by 77%, decrease the risk of treatment failure by 53% and the risk of sputum purulence by 44%; with a small increase in the risk of diarrhoea These results should be interpreted with caution due to the differences in patient selection, antibiotic choice, small number of included trials and lack of control for interventions that influence outcome, such as use of systemic corticosteroids and ventilatory support. Nevertheless, this review supports antibiotics for patients with COPD exacerbations with increased cough and sputum purulence who are moderately or severely ill".

Choice of antibiotics is an area where not a great deal of evidence exists. Most initial trials were with Amoxicillin, Doxycyclin and Septra. However, these antibiotics are no longer considered first-line for treatment of pathogens such as H.Flu and M. catarrhalis that maybe responsible for COPD exacerbations. When deciding on the antibiotic choice, risk factors such as older age (>65 years), comorbid conditions (especially cardiac disease), severe underlying COPD (defined as FEV1 <50 percent), frequent exacerbations (three or more per year), and antimicrobial therapy within the past three months should be taken into account.

The GOLD guidelines recommend antibiotic therapy for patients with:

1) Severe exacerbation requiring mechanical ventilation
2) With three cardinal symptoms of increased sputum purulence plus either increased dyspnea or increased sputum volume
(thought they don’t provide any guidance regarding the choice of antibiotics)

WITHDRAWN: Antibiotics for exacerbations of chronic obstructive pulmonary disease.
Ram FS, Rodriguez-Roisin R, Granados-Navarrete A, Garcia-Aymerich J, Barnes NC. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD004403.

4 for 2, 2 for 4

2011-08-24T10:14:00.003-04:00

This morning we reviewed the drugs involved in treatment of active tuberculosis.

The initial phase of treatment usually consists of two months of therapy with four drugs--typically isoniazid, rifampin, pyrazinamide, and ethambutol. The continuation phase in most cases consists of isoniazid and rifampin for four months (remember “4 for 2, 2 for 4”).

Treatment requires careful monitoring for drug toxicity. Baseline transaminases, bilirubin and ALP, CBD, creatinine, and uric acid should be obtained. When starting ethambutol, patients should be referred to ophthalmology for visual acuity and red-green color discrimination testing. Patients should be monitored closely for signs of hepatic toxicity.

Here is a recent update on TB management.
Current concepts in the management of tuberculosis. Sia IG, Wieland ML. Mayo Clin Proc. 2011 Apr;86(4):348-61

* Ghon's complex, seen in left middle field in the above image, is a lung lesion caused by tuberculosis that consists of a calcified focus of infection and an associated lymph node.

The Right dose at the Right time

2011-08-22T09:44:00.007-04:00

This morning we discussed a case of fever and headache. We reviewd the approach to diagnosis and treatment of bacterial meningitis. Two key points from our discussion were:

1. Antibiotic therapy should not be delayed for any reason and should be given immediately after blood cultures are obtained. Dexamethasone should be given shortly before or at the same time as the first dose of antibiotics, when S. pneumoniae is suspected.

2. The "meningitis doses" of the empiric antibiotics in patients with normal renal function is: Vancomycin 1.5-2g IV q12, Ceftriaxone 2 g IV every 12 hours, and if Listeria suspected Ampicillin 2gr IV q4hr.

Here is a previous post on Meningitis.

*Steptococcus Pneumoniae, a gram postive cocci in chains, is the most common cause of community acquired bacterial meningitis in adults.

A case of bloody diarrhea

2011-08-19T09:45:00.004-04:00

Today we discussed a case of bloody diarrhea caused by Enterohemorrhagic E. coli (EHEC), strain O157: H7.

Patients with this infection generally present with bloody diarrhea, mild leukocytosis, abdominal pain, but no fever. This bacteria produces a toxin called the Shiga toxin which can result in the dreaded Hemolytic-uremic syndrome (HUS)- the major systemic complication of EHEC infection. HUS is characterized by the triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia

The treatment of EHEC infection consists of supportive care and monitoring for the development of microangiopathic complications. Administering antibiotic therapy to patients with EHEC is not recommended (Grade 1B- though the evidence is only in children <10).

Here is a review article on the topic.

Escherichia coli O157:H7 and the hemolytic-uremic syndrome.Boyce TG, Swerdlow DL, Griffin PM. N Engl J Med. 1995;333(6):364.

* Romanian greenhouse employees destroy tons of cucumbers for fear of E. coli. In May 2011, a new Shiga toxin-producing EHEC strain, O104:H4, was identified as the cause of an outbreak in Germany and other countries in Europe.

"a case of abnormal bone softening"

2011-08-17T14:04:00.003-04:00

We talked about a case of newly diagnosed Multiple Myeloma. Here is a previous blog post on the topic.

*Sarah Newbury, the first reported patient with multiple myeloma. (A) Bone destruction in the sternum. (B) The patient with fractured femurs and right humerus. (C) Bone destruction involving the femur. Reported by Solly 1844.

Combined ASA and Plavix in setting of Acute Stroke

2011-08-11T14:35:00.002-04:00

This morning we talked about the evidence behind dual therapy with ASA and plavix in the setting of acute stroke.

A large study called the MATCH trial, with over 7500 patients, did not find any benefic with the combined use of aspirin and clopidogrel but found significant increase in the risk of bleeding complications.

The FASTER trial, a much smaller study with 392 patients with TIA or mild stroke, compared either aspirin plus clopidogrel (300 mg loading dose, then 75 mg daily) or aspirin alone. The trial ended prematurely due to slow recruitment. At 90 days, there was no statistically significant difference between the groups but a trend toward decreased primary outcome measure of combined ischemic and hemorrhagic stroke (7.1 versus 10.8 percent).

Silk Road Disease

2011-08-10T09:33:00.005-04:00

This morning we discussed a case of oral ulcers and our differential diagnosis included Behcet’s disease.

This disorder is a systemic vasculitis that can effect veins of variable sizes. The disease is characterized by relapsing episodes of oral and genital ulcers, skin lesions, and ocular lesions, and can affect other systems including vascular, gastrointestinal, and neurological systems.

It occurs most frequently in an area that coincides with the Old Silk Route, so the disease is sometimes referred to as the Silk Road Disease.

Mainstay of treatment is immunosuppression with corticosteroids, azathioprine, cychlophosphamide, cyclosporine A, and more recently biologics including interferon-alpha, anti-tumour necrosis factor alpha agents.

Here is a recent feview article on the topic.

Behçet's disease--a contemporary review. Mendes D, Correia M, Barbedo M, Vaio T, Mota M, Gonçalves O, Valente J. J Autoimmun. 2009 May-Jun;32(3-4):178-88. Epub 2009 Mar 26.

* The image is a picture of Hulusi Behçet, a Turkish dermatologist and scientist who first described the illness in 1936.

Tachycardia-induced Cardiomyopathy

2011-08-09T09:41:00.004-04:00

We discussed a case of tachycardia-induced cardiomyopathy this morning. This condition results from prolonged periods of rapid ventricular heart rates, and often improves with heart rate control with a good prognosis in most patients.

Patients may present with palpitations, fatigue, decreased exercise tolerance, or symptomatic congestive heart failure.

Treatment of tachycardia-mediated heart failure is the same as any other heart failure (eg, ACE or ARB inhibitors, beta blockers, diuretics), with aggressive control of heart rate.

Here is a recent review article on the topic

Tachycardia-induced cardiomyopathy: evaluation and therapeutic options. Lishmanov A, Chockalingam P, Senthilkumar A, Chockalingam A. Congest Heart Fail. 2010 May;16(3):122-6.

* Chest x ray showing cardiomegaly (panel A) in a patient with tachycardia (panel B). Panel C shows improved cardiomegaly after 3 months of aggressive heart-rate control (panel D). Images in Cardiology. Heart 2001;86:642.

Diabetic Autonomic Neuropathy

2011-08-08T10:59:00.007-04:00

This morning our we talked about diabetic autonomic neuropathy (DAN) in long-standing diabetes.

DAN is a common and distressing complication that can affect any or all parts of the autonomic nervous system (ANS). Many organs are innervated dually by the parasympathetic and sympathetic fiber. DAN can cause hypo- or hyperactivity of each or all parts of the ANS.

Clinical manifestations can include the cardiovascular system (tachycardia, exercise intolerance, cardiac denervation leading to silent ischemia, orthostatic hypotension), GI system (esophageal dysfunction, gastroparesis, diarrhea or constipation, fecal incontinence), GU system (erectile dysfunction, neurogenic bladder), skin (impaired sweating), and metabolic dysfunction(hypoglycaemia unawareness).

Here a review article on the topic.
Diabetic autonomic neuropathy. Vinik AI, Freeman R, Erbas T. Semin Neurol.(4):365-7.

* A plain abdominal radiograph showing a very dilated stomach (arrows) secondary to diabetic autonomic neuropathy (Images in Clinical Medicine NEJM)

Water Intoxication

2011-08-05T09:30:00.004-04:00

This morning, we discussed a case of hyponatremia.

Remember that disorders of sodium are really problems with water balance, so it is helpful to think of hyponatremia as excess free water. Prior to being able to test for serum sodium concentrations, the clinical syndrome that is now known as hyponatremia, characterized by confusion, muscle cramps, fatigue, delirium, seizures, and death, was called “water intoxication” syndrome.

Here are two previous post on hyponatremia.
Hyponatremia
Hyponatremia - no it's Hyperhydroemia

* MRI scan of person with central pontine myelinolysis (Saggital view, the dark area inside the circle is the region of damage). CPM is a devastating consequence of rapid fluctuations in sodium status.

Equilibrium

2011-08-04T16:30:00.005-04:00

Today in morning report a few of the presented cases had disorders of equilibrium with the two cardinal symptoms of either vertigo – an illusion of bodily or environment spinning- or ataxia- incoordination of limbs or gait.

Disorders of disequilibrium can be produced by conditions that affect the vestibular pathways, the cerebellum, or sensory pathways in the spinal cord or peripheral nerves.

We considered the diagnosis of stroke in all of the above cases. A recent article in CMAJ called "Does my dizzy patient have a stroke" addresses that same question. Here is the article.

*Jean Louis Forain's 19th Century Tightrope Walker. How many organ systems is the performer using to maintaining her balance in the dark?

Is This Patient Malnourished?

2011-08-03T14:20:00.008-04:00

In our physical exam rounds today, we examined a patient for signs of malnutrition, and reviewed the JAMA RCE article on the topic.

The gist of the articles is to know the “Subjective Global Assessment” which includes the following:
•History (Weight change,Dietary intake change,GI symptoms,Functional capacity)
•Physical exam (Loss of subcutaneous fat, Muscle wasting, Edema)

Based the above, you can categorize patients into “well-nourished”, “moderately malnourished”, or “severely malnourished”. These categories then correlate with patient likelihood of being admitted, and post-operative complications.

Here is the article.
http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed?term=is%20this%20patient%20malnourished%20detsky%20JAMA

* Given our topic of conversation, I like to remind everyone of the famine in East Africa. A devastating drought and crumbling infrastructure have created one of the worst hunger emergencies in our generation. If you would like to make a donation, the Government of Canada has created the East Africa Drought Relief Fund, and will match your donations.

An aspirin a day? ASA in secondary prevention of CVD.

2011-08-03T10:57:00.005-04:00

This morning we briefly mentioned the Antithrombotic Trialists' Collaboration overview article. This group reviewed the results of 195 randomized trials of aspirin, among more than 135,000 high-risk patients with prior history of cardiovascular or cerebrovascular events. The following are the major conclusions:

• Aspirin, significantly reduced the relative risk of subsequent vascular events (nonfatal MI, nonfatal stroke, and vascular death) by approximately 22 percent.
• There was no difference in efficacy between doses of 75 to 150 mg/day (called low-dose aspirin) and 160 to 325 mg/day (called medium-dose aspirin).

Here is the link to the paper if you like.
Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Antithrombotic Trialists' Collaboration. BMJ. 2002;324(7329):71.

http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed?term=BMJ.%202002%3B324(7329)%3A71.

* A French advertisement for aspirin from 1923. Aspirin (name originally coined by they Bayer company in 1897) lost its status as a registered trademark became a generic name in many countries. Today, Aspirin, with a capital "A", remains a registered trademark of Bayer Canada.

...and the QT was 580!!

2011-07-28T10:03:00.004-04:00

Amuse-Bouche at today’s morning report was prolonged QT interval on the ECG. This conditions is associated with an increased risk of torsades de pointes, which is a life threatening polymorphic ventricular tachycardia.

Long QT can be genetic or acquired. Drugs are a common cause of prolonged QT. Among them are:
• Antiarrhythmic drugs such as sotolol, amiodarone, quinidine, procainamide
• Macrolide and floquinolone antibiotics
• Certain psychotropic medications like TCAs, haloperidol, methadone

Drug-induced prolonged QT is an idiosyncratic event, but there are some identified risk factors.
• Rapid IV infusion of the drug
• Electrolyte abnormalities (hypokalemia, hypocalcemia or hypomagnesemia)
• Use of other drugs known to prolong the QT interval
• Congenital long QT syndrome
• Underlying cardiac abnormalities
• Hypothyroidism
• Females
• Patients with stroke

Here is a review article on the topic.
Long QT syndrome: diagnosis and management. Khan IA. Am Heart J. 2002 Jan;143(1):7-14
http://www.ncbi.nlm.nih.gov/pubmed/11773906

* The term “torsade de pointes” means “twisting around the points in ballet where the dancer rotates around an imaginary axis. On the ECG, the QRS complex appears to twist around the electrical baseline with a continuously changing point of origin, reminiscent of the ballet movement.

Ascites

2011-07-27T14:44:00.004-04:00

We talked about examination manoeuvres for clinically diagnosing ascites today in our physical exam rounds. Here is a good review of the topic in a previous post.

http://morningreporttwh.blogspot.com/2009/07/ascites.html

* The image is a painting of Bacchus, the Greek god of wine by Henri Millot,1730. How many stigmata of alcoholic cirrhosis can you identify in him?

Is it hot enough yet?

2011-07-26T14:05:00.004-04:00

Given the recent heat wave in Toronto, morning report was aptly about a case of heat stroke today. As we discussed today, the most important causes of severe hyperthermia (greater than 40ºC) are heat stroke, neuroleptic malignant syndrome, thyroid strom, and malignant hyperthermia.

Heat stroke is diagnosed based on history, physical examination and the context in which symptoms developed (eg, high temperature and no air conditioner). Diagnostic studies are nonspecific. Heat stroke can cause cardiovascular, renal, or hepatic dysfunction or coagulopathy.

The management of heat stroke consists of ABC, rapid cooling, and treatment of complications.

Here is a recent review of the topic.

Heat-related illness. Becker JA, Stewart LK. Am Fam Physician. 83(11):1325-30
http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed/21661715

Toxic Epidermal Necrolysis

2011-07-25T19:48:00.005-04:00

This morning we discussed an unsolved mystery that involved a skin biopsy showing TEN. Toxic Epidermal Necrolysis (TEN) a severe type of hypsersensitivity reaction, affecting the skin and mucus membranes, that occurs in response to medications and some infections.

Treatment includes stopping the offending agent and supportive care including treating the complications such as superimposed skin infections.

Here is a recent review on the topic if you like to read more!
Toxic epidermal necrolysis and Stevens-Johnson syndrome: a review.
Gerull R, Nelle M, Schaible T. Crit Care Med. 2011 Jun;39(6):1521-32.

*The above picture is Mycoplasma pneumoniae, which is rarely associated with TEN

Systemic Lupus Erythematosis

2011-07-22T09:26:00.006-04:00

This morning, we discussed a case of first presentation of lupus. Here is post from last year on the topic
http://morningreporttwh.blogspot.com/2010/07/systemic-lupus-erythematosus.html

* Contrary to popular belief, British singer Seal wasn't bitten by a seal and didn't wrestle a wild boar. His facial scars are manifestations of discoid rash of lupus.<

Neurologic Manifestations of Vitamin B12 Deficiency

2011-07-21T09:49:00.005-04:00

In our discussion this morning about the causes of “fall and dementia” we briefly touched on Vitamin B12 deficiently. Vitamin B12 is a water soluble present in animal products (meat and dairy). B12 is involved in myelin synthesis, and hence, it’s deficiency has neurologic consequences.

Neurologic manifestations of B12 deficiency is the classic subacute combined degeneration of the dorsal (posterior) and lateral spinal columns. SCD manifests as symmetrical primarily lower limb neuropathy with loss of vibration and position sense, which can result in ataxia.

Other neurologic findings in B12 deficiency include axonal degeneration of peripheral nerves and central nervous system symptoms including memory loss, irritability, and dementia.

Interestingly, not all patients with neurologic abnormalities secondary to Vit B12 deficiency have hematologic manifestations.

Here is good review of B12 deficiency.
Current concepts in the diagnosis of cobalamin deficiency. Green R, Kinsella LJ. Neurology. 1995;45(8):1435.

*the picture is an axial image of the spinal cord of a patient with B12 Deficiency. Blue is where myeline is stained and you can see the loss of myeline latterally and posteriorly.

Cutaneous Manifestations of Sarcoid

2011-07-20T09:16:00.004-04:00

Sarcoidosis is a multisystem disease characterized by the presence of noncaseating granulomas in tissues such as the skin, lung, lymph nodes, eyes, joints, brain, kidneys, and heart. Cutaneous lesions may present with a variety of morphologies, including papules, nodules, plaques, and infiltrated scars.

One-third of patients with sarcoidosis have skin lesions. These lesions can be the presenting finding of the disease. Some of these lesions are nonspecific, but others are highly suggestive of sarcoidosis. There are many different types of lesions.

Here are a few common skin findings in Sarcoidosis:
Lupus pernio (first picture) : Lupus pernio is a violaceous or erythematous indurated papules, plaques, or nodules that are primarily distributed on the central face (though can also happen in the extremities and buttocks)
Erythema nodosum (second picture): raised tender inflammatory nodules over lower legs. Common and non-specific.

If you’re interested in reading more on sarcoidosis, here is a great review article.

Sarcoidosis. Michael C. Iannuzzi, M.D., Benjamin A. Rybicki, Ph.D., and Alvin S. Teirstein, M.D.N Engl J Med 2007; 357:2153-2165.
http://www.nejm.org/doi/full/10.1056/NEJMra071714

Disseminated Gonococcal Infection

2011-07-19T10:10:00.002-04:00

Stephan Russ, M.D., and Keith Wrenn, M.D. N Engl J Med 2005; 352:e15April 21, 2005

In our morning report discussion today, this image from NEJM was mentioned. The image shows the classic macular (arrows) and pustular lesions (arrowheads)seen in disseminated gonococcal infection.

Seizures in HIV-infected Patients

2011-07-19T09:50:00.004-04:00

Today, morning report was a discussion of seizures in patients with HIV. Seizures are common in HIV positive individuals. Always think of HIV-related causes and non-HIV-related causes.

HIV-Related causes of seizure included direct cerebral HIV infection, CNS lymphoma, and opportunistic infections such as CNS Toxoplasmosis (most common), Cryptococcal meningitis, CNS TB (tuberculoma rather than TB meningitis). PML is a possible but uncommon cause of seizures. Some medications (such as Foscarnet used to in treatment of CMV infection) can provoke seizures as well.

Don’t forget the other common causes of seizures in adults such as bacterial meningitis, electrolyte and metabolic disturbances, and drug/EtOH intoxication/withdrawal.

Here is a great review on the topic.
Seizures in HIV-seropositive individuals: NIMHANS experience and review. Satishchandra P, Sinha S. Epilepsia. 2008 Aug;49 Suppl 6:33-41.
http://www.ncbi.nlm.nih.gov/pubmed/18754959

* The image is a CT scan slice showing a ring-enhancing lesion with an eccentric nodule, which also enhances. The corticomedullary location and marked surrounding edema are characteristic of toxoplasmosis.

Aspirin Toxicity

2011-07-18T10:21:00.002-04:00

This morning we discussed a case of ASA toxicity. This is a potentially fatal clinical scenario that can occur with acute or chronic ingestion of ASA.

At supertherapeutic doses, ASA absorption is delayed because of pylorspasm and “cement” formation. At high doses, the elimination is via slow renal excretion.

Patients often present with nausea, vomiting, tachypnea, and tinnitus. Altered LOC, ranging from mild to coma, and non-cardiogenic pulmonary edema are severe consequences of ASA toxicity. Investigations often show an anion-gap metabolic acidosis and a respiratory alkolosis (secondary to direct stimulation of the respiratory centre).

Main principles of management are supportive care (A-B-Cs), GI decontamination by activated charcoal, and alkalanization of plasma and urine. Don’t forget to call poison control for any overdose, and check for other co-ingestions.

Give a glucose-containing IVF even in the presence of normal serum glucose as ASA can decrease CNS glucose levels. Call nephrology early as hemodialysis is our ultimate treatment for patients who deteriorate despite supportive care.

Uptodate has a really good review on the topic if you’re interested.

Tumour Lysis Syndrome

2011-07-15T10:03:00.005-04:00

This morning we had an engaging discussion about Tumour Lysis Syndrome (TLS). As was also reviewed yesterday at noon rounds, TLS is an oncologic emergency.

It is caused by massive tumor cell lysis with the release of large amounts of potassium, phosphate, and nucleic acids Breakdown of nucleic acids to uric acid leads to hyperuricemia, and the precipitation of uric acid in the renal tubules causes acute renal failure. Calcium phosphate deposition can also contribute to renal failure.

Initiation of cytotoxic therapy in patients with high-grade lymphomas (particularly Burkitts lymphoma) and acute lymphoblastic leukemia is often the trigger to TLS. However, TLS can occur spontaneously.

Management of TLS consists of aggressive intravenous hydration, and the administration of the hypouricemic agents rasburicase (recombinant uric oxidase) or allopurinol.

Here is a recent review on the topic:

The Tumor Lysis Syndrome. Scott C. Howard, M.D., Deborah P. Jones, M.D., and Ching-Hon Pui, M.D.N Engl J Med 2011; 364:1844-1854.
http://www.nejm.org/doi/full/10.1056/NEJMra0904569

2011-07-13T09:57:00.008-04:00

Familial Mediterranean Fever

FMF is a rare autosomal recessive disorder characterized by paroxysms of fever and serosal inflammation, seen primarily in several ethnic groups originating in the Mediterranean region. Typical clinical presentations of the disease are recurrent attacks of severe pain (due to serositis at one or more sites) and fever, lasting one to three days, and then resolving spontaneously. In between attacks, patients are entirely well.

Common manifestation are peritonitis, pleuritis, synovitis and an erysipelas-like skin lesion. Other less common findings are pericarditis, orchitis and recurrent aseptic meningitis also can occur. As was mentioned this morning, an increased incidence of some vasculitides, such as polyarteritis nodosa and Henoch-Schönlein purpura, has been described. Kidney involvement with these processes may be particularly common.

As discussed this morning, the most important long term complication of FMF is secondary (AA) amyloidosis which occurs insidiously and progressively. Amyloid A deposition occurs in the kidney, spleen, liver, and gut. Renal involvement is the dominant feature of FMF-related amyloidosis.

Colchicine is the mainstay of treatment of FMF, both to prevent attacks as well as prevent the development and progression of amyloidosis. Research is underway evaluating the role of anti-TNF-alpha therapy and IL-1 receptor blockade in severe FMF.

Here two good articles are treatment and clinical manifestations of FMF if you're interested.
http://www.ncbi.nlm.nih.gov.myaccess.library.utoronto.ca/pubmed/19530512
Familial Mediterranean fever. Ben-Chetrit E, Levy M. Lancet. 1998;351(9103):659.

Hepatocellular Carcinoma Risk Factors

2011-05-05T09:37:00.009-04:00

A number of important risk factors for the development of hepatocellular carcinoma (HCC) have been identified, including the following:

- Hepatitis B carrier status
- Chronic hepatitis C infection
- Cirrhosis of almost any cause
- Hereditary hemochromatosis
- Environmental toxins (alfatoxin that commonly contaminates corn, soybeans and peanuts; contaminated drinking water; betel nut chewing)
- Tobacco and alcohol abuse
- Non-alcoholic fatty liver disease and diabetes mellitus
- Alpha-1 antitrypsin deficiency
- Epidermal growth factor polymorphisms

Also, it should be noted that HCC has been known to occur in patients without any identifiable risk factor.

For the coffee-lovers among us: several observational studies have implicated coffee consumption as a protective factor for liver cancer, including HCC. A meta-analysis estimated that consumption of two or more cups per day was associated with a 43% reduction of liver cancer. The benefit was observed in individuals with and without liver disease. The presumed mechanism surrounds the fact that coffee contains large amounts of antioxidants suggesting biological plausibility for the protective effect. The authors also noted that coffee and caffeine have been linked to lower liver enzyme levels and a reduced risk of cirrhosis, potentially further contributing to biological plausibility (Larsson SC, Wolk A. Coffee consumption and risk of liver cancer: a meta-analysis. Gastroenterology. 2007;132(5):1740)

Diarrhea in HIV-infected patients

2011-04-28T09:34:00.002-04:00

Diarrhea can cause significant morbidity in HIV-infected patients, and can be due to a myriad of causes from infectious pathogens, malignancy and even medications. Before the use of HAART, chronic diarrhea was a large cause of AIDS-defining conditions. However, in the current era the infectious causes of diarrhea in HIV-infected individuals in declining. Key to the evaluation of diarrhea in HIV-infected individuals is a thorough history that includes duration of symptoms, frequency and characteristics of stool, amount of weight loss, and the presence of other abdominal symptoms and constitutional symptoms. Additionally, all medications should be reviewed. A careful physical examination is key to help determine the degree of wasting or to identify any particular findings that may point to specific diseases. For example, fever and wasting may suggest an underlying opportunistic infection. Initial investigations should include stool examination and cultures, and blood cultures. Abdominal CT imaging and endoscopy may be considered if the initial non-invasive work-up is non-diagnostic.

Below is a list of several key causes of diarrhea in HIV-infected individuals:

Bacterial: salmonella, campylobacter, MAC, TB, C. difficile, shigella
Viral: CMV, herpes simplex, adenovirus, norwalk
Protozoal: microsporidium, cryptosporidium
Fungal: histoplasmosis, coccidiomycosis
Gut neoplasms: lymphoma, Kaposi’s sarcoma
Pancreatic insufficiency
Infectious pancreatitis: CMV, MAC
Drug-induced pancreatitis: didanosine, pentamidine
Tumor invasion: lymphoma, Kaposi’s sarcoma
Idiopathic: “AIDS enteropathy”

Is my patient delirious?

2011-04-21T09:27:00.004-04:00

Delirium is a very common medical problem in elderly patients admitted to hospital. The 4 key features that characterize delirium include: (1) disturbance of consciousness with reduced ability to focus, sustain, or shift attention; (2) a change in cognition or the development of a perceptual disturbance that is not better accounted for by a pre-existing, established, or evolving dementia; (3) the disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day; and (4) there is evidence from the history, physical examination, or laboratory findings that the disturbance is caused by a medical condition, substance intoxication, or medication side effect.

The Confusion Assessment Method (CAM) is a simple tool that can be used by clinicians to integrate their observations and identify when delirium is the most probable diagnosis. In medical and surgical settings, the CAM has a sensitivity of 94-100% and a specificity of 90-95%.

Confusion assessment method (CAM) for the diagnosis of delirium

1. Acute onset and fluctuating course
- Usually obtained from a family member or nurse and shown by positive responses to the following questions: "Is there evidence of an acute change in mental status from the patient's baseline?"; "Did the abnormal behaviour fluctuate during the day, that is, tend to come and go, or increase and decrease in severity?"

2. Inattention
- Shown by a positive response to the following: "Did the patient have difficulty focusing attention, for example, being easily distractible or having difficulty keeping track of what was being said?"

3. Disorganized thinking
- Shown by a positive response to the following: "Was the patient's thinking disorganized or incoherent, such as rambling or irrelevant conversation, unclear or illogical flow of ideas, or unpredictable switching from subject to subject?"

4. Altered level of consciousness
- Shown by any answer other than "alert" to the following: "Overall, how would you rate this patient's level of consciousness?"
Normal = alert
Hyperalert = vigilant
Drowsy, easily aroused = lethargic
Difficult to arouse = stupor
Unarousable = coma

The diagnosis of delirium requires the presence of features 1 AND 2 plus either 3 OR 4.

Does my patient have COPD?

2011-04-15T09:28:00.010-04:00

We are often faced with many patients who are given a label of obstructive airway disease based on a history of smoking and wheezing. But in many instances patients with these features do not have obstructive airway disease. Dr. Straus and colleagues identified 4 elements on history and physical examination that were significantly associated with a diagnosis of obstructive airway disease:

1. Smoking at least 40 pack-years (LR + 8.3)

2. Self-reported history of chronic obstructive airway disease (LR + 7.3)

3. Maximum larygeal height less than 4cm (LR + 2.8)

4. Age at least 45 yrs (LR + 1.3)

The presence of all 4 of these elements has a LR + 220, rulling in a diagnosis of obstructive airway disease.

Click on the following link to see the abstract: http://http//jama.ama-assn.org/content/283/14/1853.abstract

Adrenal Insufficiency

2011-04-14T09:20:00.006-04:00

The clinical presentation of adrenal insufficiency is variable and depends on whether the onset is acute (leading to adrenal crisis) or chornic, with symptoms that are often vague and insidious. The key to making the diagnosis of adrenal insufficiency is a high level of clinical suspicion. The signs and symptoms of adrenal insufficiency depend upon the rate and extent of loss of adrenal function, whether mineralocorticoid production is preserved, and the degree of stress. The following is a list of key clinical features of primary adrenal insufficiency:

weakness

fatigue

anorexia

orthostatic hypotension

nausea

vomiting

The following is a list of key laboratory abnormalities of primary adrenal insufficiency:

hyponatremia

hyperkalemia

hypoglycemia

lymphocytosis

eosinophilia

hypercalcemia (rarely)

Patients with Headache

2011-04-12T09:00:00.008-04:00

Headaches are a very common medical complaint. In assessing patients with headaches, we must determine who has a serious cause of a headache and who requires neuroimaging. A Rational Clinical Exam article from JAMA entitled "Does this patient with headache have a migraine or need neuroimaging?" helps to outline an approach to headache. After a systemic review of the literature, the best predictors of a migraine were summarized by the mnemonic POUNDing: Pulsation, duration of 4-72 hOurs, Unilateral, Nausea, Disabling). If a patient meets 4 out of the 5 criteria, the likelihood ratio (LR) for definite or possible migraines is 24. For neuroimaging, several clinical features were found on pooled analysis to predict the presence of a serious intracranial abnormality: cluster-type headache (LR 10.7), abnormal findings on neurological examination (LR 5.3), undefined headache (LR 3.8), headache with aura (LR 3.2), headache aggrevated by exertion or valsalva (LR 2.3), and headache with vomiting (LR 1.*). It should be noted that no clinical features were useful in ruling out significant pathologic conditions. To see the full Rational Clinical Exam article click here http://jama.ama-assn.org/content/296/10/1274.full.pdf+html?sid=80cae855-c34e-401a-a365-34f964dfe247

Dabigatran for anticoagulation in Afib

2011-04-07T10:09:00.005-04:00

Dabigatran is an oral, direct thrombin inhibitor. Its efficacy and safety relative to warfarin was evaluated in the RE-LY trial, at 2 doses. It was the first randomized trial to demonstrate that an alternative oral anticoagulant is superior to adjusted-dose warfarin. Over 18,000 patients with non-valvular atrial fibrillation and at least 1 stroke risk factor were were randomly assigned to receive oral dabigatran at one of two doses (110 or 150 mg) twice daily, or adjusted dose warfarin (INR 2-3). The primary study outcome was stroke or systemic embolism. After a median follow-up 2 years, rates of the primary outcome were 1.69%/yr in the warfarin group, compared with 1.53%/yr in the group that received 110 mg of dabigatran (P<0.001), and 1.11%/yr in the group that received 150 mg of dabigatran (P<0.001). The rate of major bleeding was higher in the warfarin group, compared to the lower dose dabigatran group. This study concluded that in patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. To see the full article click here http://www.nejm.org/doi/full/10.1056/NEJMoa0905561#t=article

Clubbing

2010-11-17T09:52:00.002-05:00

Today in morning report we discussed a patient, who among other problems, was clubbed.

Clubbing is the enlargement of the terminal segments of the fingers and/or toes that results from the proliferation of the connective tissue between the nail matrix and the distal phalanx. It develops in the context of a number of neoplastic, infectious, inflammatory and vascular conditions.

Features on physical exam that make clubbing more likely include changes in nail-fold angles, as well as changes in the shape, depth, and width of the terminal phalanges.

1) Phalangeal Depth - This ratio compares the depth of the distal phalanges to the inerphalangeal areas. Normally, this is less than 1. Once this ratio exceeds 1, clubbing is more likely.

2) Nail Fold angles - Two angles are commonly discussed: the profile angle and hyponychial angle.

a) The profile angle can be estimated by the angle the nail projects from the nail fold. normally this is about 160 degrees but exceeds 180 degrees when the finger is clubbed.

b)The hyponychial angle compares two lines, (1), from the DIP joint to the nail fold and (2), from the nail fold to the point where the nail meets the finger tips. This angle is should not exceed 190 degrees normally and if it does, clubbing is likely present.

3) Nail bed squishiness - Palpation of the nail bed in clubbed fingers tends to be spongier than a normal nail with the sensation that the nail is floating.

Check out the JAMA rational clinical exam series here for an evidence based review.

Grade 4 Left Ventricles

2010-11-15T09:35:00.015-05:00

Today in morning report, we discussed a patient presenting with complications related to their grade-4 left ventricle. Much of our discussion focused on the management of these patients. Specifically, what about device therapy? Here is a summary:

Device Therapy
This really came to the forefront with the MADIT-2 trial where patients with a history of MI and severe LV dysfunction (grade 3 or worse) after optimal medical therapy had prophylactic ICDs placed. This showed improved survival. The SCD-HeFT trial looked at amiodarone vs. ICDs and again, device therapy appeared superior. Cost effective analysis has been favourable, but controversial. Check out this editorial for another look.

The MADIT-CRT trial looked at relatively asymptomatic patients (NYHA class 1 and 2) with depressed LV function (less than 30%) and prolonged QRS durations and found that CRT decreased rates of CHF exacerbations.

Recently, results of the RAFT trial were presented in NEJM and found that "among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure." More adverse events were noted, however.

All in all, this is a rapidly progressing area in medicine and it may not be too long until we find ourselves here!

Toxic Epidermal Necrolysis

2010-11-12T11:34:00.003-05:00

Today in Morning Report, we discussed the case of toxic epidermal necrolysis likely secondary to allopurinol use.

Allopurinol and its metabolite, oxipurinol (alloxanthine), decrease the production of uric acid by inhibiting the action of xanthine oxidase, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid. Indications are most commonly for disorders of hyperuricemia (urate nephropathy, tumor lysis sydrome prophylaxis, and gout). When used for gout, most would agree that >3 flares/year (or tophaceous deposition) would merit its use. Incidentally discovered hyperuricemia is not an on-label indication.

With regards to the side-effect profile, the biggest concern, as seen in our patient, is toxic epidermal necrolysis. This is a very rare, but acute and potentially fatal skin reaction in which there is sheet-like skin and mucosal loss. It exists in a spectrum with Stevens-Johnson Sydrome and is mainly differentiated by the degree of epidermal involvement.

Treatment is mostly supportive but begins with the discontinuation of the offending drug. Wound care is very important to prevent excess fluid loss and secondary infections. In severe cases, consultation with a burn unit may be appropriate. Adjunct treatment with corticosteroids, cyclosporin, cyclophosphamide and IVIg have been trialed with variable success.

TEN is reviewed nicely at this link, check it out for a summary on the diagnosis and treatment.

Hyperkalemia

2010-11-10T10:44:00.003-05:00

Last week, a patient with hyperkalemia was discussed in morning report.

Causes of hyperkalemia always come down to renal handling of potassium. Dietary (or iatrogenic!) intake of potassium may play a role, but most clinical scenarios revolve around limitations in excretion.

Management options include:
1) Stop the exogenous potassium - this seems simple but is embarassing when missed.

2) Stop offending drugs - this is not the right time for any potassium sparing diuretics or ACE inhibitors

3) Shift the Potassium - This does not equal excretion and is only a temporary fix. Classically, a high glucose load (1 amp of D50W) with an intravenous insulin chaser (1o units iv) is the mainstay cocktail. Other options include intravenous sodium bicarbonate and inhaled beta agonists (8 puffs with aerochamber). Interestingly, beta agonists may be more efficacious than previously believed (see the article below).

4) Dump the Potassium - at the end of the day, you need to rid the body of the excess. A number of options exist. High dose furosemide (assuming this is not oliguric renal failure) is an effective way to mobilize potassium. Potassium binders are often used (kayexalate) but are slow and have other side effects (colonic necrosis!). Finally, hyperkalemia refractory to medical management is an indication for hemodialysis.

Check out CMAJ for a very recent review.

Aches and Pains

2010-11-09T10:19:00.004-05:00

Today we discussed an interesting case of a man with fevers and progressive muscle pain and weakness. Among the many things on the differential diagnosis was Giant Cell Arteritis.

GCA (formerly known as temporal arteritis) should be considered in patients with new headaches, abrupt onset of visual disturbances, symptoms of polymyalgia rheumatica, jaw claudication, unexplained fever or anemia, high erythrocyte sedimentation rate and/or high serum C-reactive protein.

A temporal artery biopsy is part of the workup but can be negative in some patients who have the disease (7-13% will have a negative unilateral biopsy but a postive bilateral biopsy).

The treatment for GCA are glucocorticoids. Prednisone at 1mg/kg is the commonest initial therapy with tapering initiated after 4 weeks (providing a normalized ESR).

Here is a link to a NEJM review on the topic and here is a look at the topic in the JAMA rationale clinical exam.

Vertigo

2010-10-12T15:08:00.005-04:00

Today in morning report, we discussed an approach to a patient with vertigo.

Vertigo is defined an illusory or hallucinatory sense of movement of the body. When approaching a patient with this problem, the history is quite important as patients often label "dizziness" in many ways. Once true vertigo is confirmed, a common approach to it involves dividing peripheral from central problems. Here are some contrasting points:

-Direction of nystagmus - Peripheral: Unidirectional, Central: Bidirectional or Unidirectional
-Purely horizontal nystagmus with no torsional component - Peripheral: Rare, Central: Common
-Vertical or purely Torsional nystagmus - Peripheral: Rare, Central: May be present
-Visual Fixation - Peripheral: inhibits nystagmus, Central: no effect
-Tinnitus - Peripheral: often present, Central: usually absent
-Associated central abnormalities - Peripheral: None, Central: Common

Finally, the Dix-Hallpike manuevers can help prove that the vertiginous symptoms are positional. This is thought to be secondary to a malpositioned canalith errantly stimulating the nerves in the vestibular apparatus. The Epley manuevers are designed to reposition the canalith. Here is a link to a short article explaining how to perform this.

Finally, here is a review looking at the approach to a chronically dizzy patient.

Meet me at the club

2010-10-01T09:30:00.005-04:00

Today in Morning Report, we discussed a variety of cases. Among them was an interesting case of a patient who experienced a syncopal event and on initial assessment, was found to be hypoxic with a normal chest radiograph. Causes of hypoxia can include:

1)Respiratory Hypoxia - This refers a situation when respiratory failure leads to hypoxemia.
Most commonly, this is caused by ventilation-perfusion mismatch (ventilation to areas of the lung that are not perfused) as can occur with a PE. Hypoventilation can also be a cause of hypoxia, but this is classically associated with increases to the PaCO2. A third cause is shunting of blood away from parts of the lung that are oxygen rich (perfusion to diseased lung) as can occur in pneumonia or atelectasis.

2) Hypoxia Secondary to High Altitude - The available oxygen for respiration is a consequence of the atmospheric pressure. Recall that the pAO2 = FI02(Patm-PH2O) - (PaCO2/RQ)*. As the atmospheric pressure drops, so does the quantity of oxygen available at the alveolus for inspiration.

3)Hypoxia Secondary to Right-to-Left Extrapulmonary Shunting - A portion of arterial blood bypasses the lung and, as such, is not oxygenated.

4) Anemic Hypoxia - The bulk of oxygen is carried in the blood by hemoglobin. If the concentration of hemoglobin is too low, the ability to carry oxygen in the blood is compromised.

5) Carbon Monoxide (CO) Intoxication - Carboxyhemoglobin (COHb) does not readily dissociate oxygen and this leads to tissue hypoxia.

6) Circulatory Hypoxia - With decreases in effective circulation, more oxygen content is extracted at the tissue level. This leads to poorer oxygen content in the venous return to the heart and subsequent hypoxia.

* PAtm = Atmospheric Pressure, PH2O= Water vapour Pressure, PaCO2 = Arterial Carbon Dioxide pressure, FIO2 = fractional inspired O2 content, RQ=respiratory quotient.

Variceal Hemorrhage

2010-09-21T09:43:00.003-04:00

Today we discussed the case of an elderly man who presented with an upper GI bleed in the setting of known cirrhosis. A variceal bleed was suspected.

Management of an upper GI bleed is a common scenario faced in our hospital's Emergency Department. Keep the following questions in mind:

1) Is my patient stable (ABCs, IV access -large bore, and on the monitor)?
2) Do they need fluid?
3) Do they need blood?
4) Are they coagulopathic?
5) What management can I initiate now (acid suppression, octreotide)?
6) Do I need to call Gastroenterology now?

Here is a link to a recent review on the management of variceal bleeds in the setting of cirrhosis.

Finally, here is a link for a review on the natural history and consequences of Hepatitis B.

Atrial Fibrillation

2010-09-20T09:40:00.003-04:00

Today we discussed a case of a critically ill patient who had atrial fibrillation with rapid ventricular response and hypotension.

From a management perspective, this can be a difficult situation as many of the agents we use to rate control patients (beta-blockers and CCBs) also have a negative inotropic effect. Amiodarone can be used intravenously but also drops blood pressure in this formulation. Alternative therapies (digoxin) may avoid this, but also seem to be less effective. D/C cardioversion may bring the patient back to sinus rhythm, but will not keep them there if the underlying issue has not been assessed.

Remember that if critical illness is driving the rhythm, aggressive therapy to the underlying cause is what counts.

If you are looking for some light reading, here are the AHA guidelines on atrial fibrillation.

Finally, this is the link for the article I mentioned comparing diltiazem to digoxin or amiodarone for rate control in atrial fibrillation.

Aortic Stenosis

2010-09-17T10:36:00.006-04:00

Today in Morning report we discussed a case of chest pain was attributed to aortic stenosis. Much of our discussion centred on the physical exam findings.

Here is a link to a previous posting that summarizes this for you.

Medical management of aortic stenosis is limited as no drug has been shown to significantly change outcomes. If the stenotic lesion is severe enough, and the patient is symptomatic, valve replacement procedures should be considered (open vs. percutaneous). Read a NEJM review here, that summarizes surgical indications.

Find the JAMA rationale clinical exam article on systolic murmurs here, and review a bedside prediction rule here.

Fever after International Travel

2010-09-16T15:08:00.003-04:00

Yesterday we discussed the classic case of fever in a returning traveler.

There are many diagnostic approaches to take in this situation but a careful travel history is often the key to the diagnosis. Never forget that when people travel, the may do riskier things then is typical for them (or that they may care to admit) both in the environment or with other people. Point is: you need to ask and you need to look.

Inquire about chemoprophylaxis, vaccines and sick contacts and take a minute to check out the country's information on the CDC website.

An oldie but goodie review from NEJM can be found here and does a nice job with the differential diagnosis.

Rashes and bleeds

2010-09-02T09:54:00.002-04:00

In Morning Report today, we ran through a number of cases. I wanted to highlight a couple of points:

Upper GI Bleeding

Discussion surrounding the medical management of upper GI bleeding focused on the role and dose of acid suppression medication. Specifically, does intravenous pantoprazole change outcomes as compared to an oral equivalent. The administration of high-dose intravenous proton-pump inhibitors while the patient is awaiting endoscopy does not appear to have an effect on the outcome, even though its use may be associated with a significant down-staging of endoscopic lesions. Whether this is cost-effective is still controversial. There is a recent NEJM review on the topic that I would encourage you to read.

Rash

Our case of the night focused on an approach to a patient with a rash involving the palms and soles. Involvement of the palms and soles minimizes the differential and includes syphilis, rocky mountain spotted fever, Enteroviral infections including Coxsackievirus and Echovirus, drug reactions and contact dermatitis. You MUST rule out syphilis in this context. Here is a BMJ review on syphilis. Check out some pictures here in CMAJ.

Kiss of the spider

2010-08-12T09:12:00.006-04:00

We discussed many interesting topics today. Here's some info on two of them.

Brown recluse spider bites: These spiders belong to the Loxosceles genus and are commonly found in the south, west and midwest US so we don't see cases in Toronto that often. The brown recluse spiders have a brownish colour with a violin like mark on their head, though victims often fail no notice the spider. Bites typically occur on the upper arm, thorax, or inner thigh and happen most commonly indoors. Bites are rare on hands and feet.

The initial brown recluse bite is painless and is followed by a red plaque that can necrose in the next 24-48h and form an eschar over the ensuing days. Systemic symptoms are rare. Treatment consists of general wound care and tetanus prophylaxis. Sometimes Dapsone is used for prevention of wound progression, but there is no evidence from human studies. Here's a good review article from NEJM on Loxosceles and other spider bites.

Treatment of AAA: We touched briefly on the relative advantages of endovascular vs. open repairs for AAA. Remember that aneurysm size is a key factor on deciding how to manage AAA:

- For aneurysms 3 - 4 cm we do survelillance with U/S every 2-3 years
- For aneurysms 4 - 5.4 cm surveillance is more frequent, every 6 mo- 1 year
- At or above 5.5 cm the risk of rupture becomes greater and consideration for repair is recommended, if the aneurysm is > 2x the diameter of the normal aorta repair is also recommended
- Any symptomatic aneurysm should be considered for repair !!!

While short term mortality for endovascular repair is lower, the 2 year outcomes show similar mortality with more complications as compared to surgery. This recent trial and its accompanying editorial give a good overview of the current thinking on the topic.

Cheers

Thrombolysis in PE

2010-08-06T09:27:00.007-04:00

Today we discussed a patient who presented with a pulmonary embolism. Indications/Evidence for thrombolysis was discussed.

To Summarize:

In 2002, a paper in NEJM compared Aleplase and Heparin vs Heparin alone and demonstrated that patients in the alteplase arm had improved clinical courses. All patients had submassive PE (and evidence of RV dysfunction or Pulmonary HTN) without arterial hypotension. This was driven by escalation of therapy in the placebo arm, not death.

A 2004 metanalysis demonstrated thrombolytic therapy compared with heparin was associated with a significant reduction in recurrent pulmonary embolism or death (9.4% versus 19.0%) in studies that enrolled patients with hemodynamically unstable PEs.

Two pro and con commentaries were published in Archives of Internal Medicine in 2005 and are good reads.

Finally, a recent NEJM review can be found here.

Overall, this is an area with uncertaintly and more RCT evidence is needed.

Rash and Fever

2010-08-04T09:43:00.002-04:00

Today we discussed an approach to a patient presenting with fever and rash who ultimately seemed to have a drug reaction to his antiretroviral medications. We focused our discussion around a differential diagnosis of a rash in this context while touching briefly on immune reonstitution inflammatory syndrome.

Drug hypersensitivity syndromes manifest as part of a triad: fever, rash and end organ involvement (hepatitis, thyroiditis, lymphadenopthy, renal failure). Stopping the offending drug and providing supportive care is the cornerstone of treatment.

With regards to timing of therapy in patients with TB and HIV, here is a NEJM article .

Panhypopituitarism

2010-08-03T09:34:00.003-04:00

Today we discussed an a case of hyponatremia that eventually led to the diagnosis of panhypopituitarism.

This can be a very difficult diagnosis to make due to the non-specific symptoms that a patient complains of (as was seen here).

Etiologies incluede;
1) Brain Damage (Traumatic, radiation, SAH, CVA, Surgery)
2) Neoplastic (originating in the pituitary or compression from outside)
3) Infectious
4) Infarction (Sheehan's, apoplexy)
5) Autoimmune
6) Infiltrative (hemochromatosis, histiocytosis)
7) Congenital

Here is a recent review from Lancet that highlights diagnosis and management.

Paraneoplastic Demyelination

2010-07-29T11:33:00.005-04:00

First, wow and thank you to Dr. Panisko for flexing his muscles and walking through the differential diagnosis of yesterday's case! We discussed, among other things, an approach to weakness with a focus on demyelinating disease. A paraneoplastic syndrome was the likely conclusion.

You can find an overview on paraneoplastic neurologic disorders here.

Here is a case report of GBS associated with an adenocarcinoma of the gallbladder (only one that I could find).

Finally, here is a review of chronic demyelinating disorders.

Venous Thrombosis

2010-07-29T10:36:00.005-04:00

Today we briefly discussed DVTs in morning report. Clinically, these can be a diagnostic challenge but clinical prediction tools are available. Check out an article in JAMA's Rational Clinical Exam series here.

We often separate severity of venous thrombosis on the basis of location (deep vs superficial). Earlier this year, a French study looked into this and found some interesting associations. Here is the link.

Finally, in our patients with COPD exacerbations of unknown cause, this article in CHEST suggests that pulmonary embolism may be the cause.

Thrombocytopenia

2010-07-27T09:47:00.004-04:00

Today we discussed an approach to thrombocytopenia. Here is a brief overview.:

Pseudothrombocytopenia:
This is a consequence of platelet clumping as a consequence of the EDTA (lavender top) tube. The presence of this leads to the platelet clumps being miscounted on the automated system. If this is an issue, order the CBC to be drawn in citrate.

Decreased Production:
The bone marrow is unable to produce platelets in sufficient quantity as a consequence of toxicity (meds, chemotherapy, alcohol), infection (viral, TB, histoplasma), replacement (cancer, fibrosis, amyloid, sarcoid), or nutrition (folate and B12 deficiency).

Sequestration:
Think of the spleen as a giant sponge and its easy to see how as hypersplenism can reduce counts. We usually see this as a consequence of portal hypertension but primary hypersplenism is also possible. Typically, counts do not drop below 1/3 of the lower limit of normal (50k) if this is the only problem.

Destruction/Consumption:
This can be broken down into mechanical (high flow over prosthetic valves, malignant HTN), immune (HIT, ITP) or consumptive (TTP, DIC) causes. TTP is a medical emergency and this is why the blood film is so important. You need to ensure that there are no schistocytes (RBC helmets) present. I will blog on TTP as a separate post in the near future. Also, remember that ITP is a diagnosis of exclusion.

Our patient was ultimately diagnosed with ITP. A great overview on diagnosis and treatment can be found here, in the recent consensus guidelines.

Legionnaire's Disease

2010-07-21T09:54:00.007-04:00

Today we discussed a case of a pneumonia that did not initially respond to empiric therapy. Supplemental investigations were notable for a positive Legionella urinary antigen.

Legionnaire's Disease was first described after an outbreak in Philadelphia in 1976. It is now being recognized as a more common cause of respiratory infections. It is a difficult to culture organism requiring special growth media (talk to the micro lab if you are thinking about it). Testing can also be done by the rapid urinary antigen assay (only detects L. pneumophilia serotype 1). Interestingly, one study demonstrated persistent urinary antigen positivity months after exposure (in an immunocompromised host).

Overall, empiric therapy for CAP (respiratory fluoroquinolones or a macrolide) should cover Legionella species and there are no RCTs that show one class to be superior to the other.

Here is a recent review.

Hydatid Cysts

2010-07-19T09:32:00.005-04:00

Today we discussed a patient with abdominal pain who had a surprising finding on his abdominal imaging.

The differential diagnosis included a hydatid cyst (Echinococcus granulosus).

Information regarding the lifecycle and pathogenesis can be found in this review.

Interestingly, in a hepatic abscess caused by Klebsiella, there is an association with DM and septic endopthalmitis.

Other causes of liver cysts are discussed here.

Systemic Lupus Erythematosus

2010-07-16T11:06:00.003-04:00

Today we discussed an unfortunate patient with multisystem disease, a positive ANA (as depicted here) and a new diagnosis of SLE.

SLE appears on the differential in many medical conditions due to the multiple organs it can involve (and the multiple manifestations required for diagnosis).

The diagnositic criteria for SLE can be found at this site.

A pathophysiologic review, with a table of the classic rhematologic antibody assays is published in NEJM here.

Have a great weekend!

Congestive Heart Failure

2010-07-13T11:18:00.007-04:00

Today, in addition to piloting another format to morning report, we discussed congestive heart failure. Management issues surrounding associated acute renal failure and atrial fibrillation were also reviewed. Here is a brief summary:

ARF

This can make management difficult. When the renal failure is secondary to poor perfusion pressure, this sometimes improves with diuresis. ACE/ARBs are vital to the management of CHF and should be continued whenever possible.

Atrial Fibrillation

This is a classic "chicken or the egg" scenario in that did the AFib push the patient into failure, or did the "atrial stretch" from fluid overload cause the patient to go into Afib? In any case, diuresis is paramount. If needed, rate controlling agents (Digoxin, Amiodarone, intravenous magnesium) can all be used to slow the patient down, but all will be ineffective without diuresis.

In both scenarios above, a trial of BiPaP can go a long way in stabilizing the patient (decreases afterload, increases preload and increases CO) while you are awaiting the effects of diuresis.

Here is a recent review on CHF from NEJM. Also, here is an interesting article on using intravenous iron therapy for iron deficient patients in heart failure.

The Adrenal Incidentaloma

2010-07-12T10:46:00.004-04:00

Today we had a great discussion on the approach to an incidentally discovered adrenal mass.

An adrenal incidentaloma is defined as an adrenal mass (>1cm) that is discovered serindipitously on abdominal imaging designed to look for something else. These are common with an estimated frequency of 6% of the general population.

Imaging characteristics
Many radiographic findings can help determine the malignant potential of a lesion. These include size (>4cm), contrast washout time, density, and border contour of the lesion.

Biochemical Workup
The basic principle is to determine whether the lesion(s) is functional or impairing the function of the gland. See Table 2 in the linked article for some guidelines on workup.

Role of Biopsy
The role of fine needle aspiration in an adrenal mass is primarily useful in determining adrenal from non-adrenal tissue (r/o mets or infection). Actual tissue architecture is required to determine if the lesion is a primary adrenocortial carcinoma. Always remember to r/o a pheochromocytoma (24h urine metanephrines) before asking someone to put a needle into these lesions (hypertensive crisis)

There is an excellent NEJM review here.

Aortic Stenosis

2010-07-09T14:51:00.007-04:00

This afternoon, physical exam rounds focused on Aortic Stenosis.

This topic was blogged about by Dr. Dave Frost (Last year's CMR) in a previous post. Here is the link.

Enjoy your weekends!

Renal Failure

2010-07-08T09:49:00.005-04:00

Today we had a fantastic discussion regarding causes of renal failure secondary to multiple myeloma.

To summarize:
Hypercalcemia
Hypercalcemia (as a consequence of bone destruction) can predispose a patient to renal failure in 3 ways. First, high calcium levels lead to a diuretic effect, reducing the effective circulating volume. Second, calcium can deposit into the kidney itself (nephrocalcinosis). Finally, the high calcium levels can precipitate in the collecting system leading to stone disease.

Stones
In addition to calcium based stones, the high cell turnover also predisposes the patient to form uric acid stone (gouty nephropathy). This can also be nephrotoxic.

Cast Nephropathy
Filtration of toxic light chains leads to both tubular injury and intratubular cast formation (and obstruction). The light chains bind avidly to the normal tubule mucoprotein (Tamm-Horsfall) and lead to obstruction. As the tubule becomes damaged, adult onset Fanconi Syndrome, a proximal type 2 RTA, can develop (loss of amino acids, glucose and ability to acidify the urine).

Light Chain Deposition Disease
Excess monoclonal light chains deposit in the kidney (without forming fibrils) and can lead to a nephrotic type syndrome.

Amyloid
Circulating light chains are taken up by macrophages where they are partially processed, then excreted as Congo-red positive, beta-pleated fibrils. These are nephrotoxic.

Recurrent Infections
Both systemic overwhelming infections (sepsis) and recurrent urologic infections are more common in myeloma patients which put them at risk for renal failure.

NSAIDS
Bone pain hurts. Patients often turn to NSAIDS to help manage the pain and this can lead to renal failure in a number of ways (will be discussed in a future blog).

Renal Vein Thrombosis
MM is a hypercoagulable state (loss of anti-thrombin 3 in the urine). The renal vein is susceptible to thrombosis and subsequent renal failure.

The "anti-kidney" antibody
Multiple antibodies against various "kidney-ness" have been described (evil-humors?) and associated with renal failure.

Cord Compression
Plasmacytoma love the spinal cord and as a consequence, cord compression can develop. A real emergency!

Pretty impressive list. If I missed something, add it to the comment section. Also, check out this article from JASN.

Listeriosis

2010-07-07T09:39:00.004-04:00

Today we discussed the interesting case of Listeriosis.

L. monocytogenes is a facultatively anaerobic, nonsporulating, gram-positive rod that grows over a broad temperature range, including refrigeration temperatures. (making small lapses in sanitation at food processing centres an even more dangerous event).

Here is a brief overview of some of the clinical manifestations.

Gastroenteritis
Usually develops within 48 hours of ingestion of a large inoculum of bacteria in contaminated foods (milk, deli meats, soft cheeses and salads). Manifestations include fever, diarrhea, headache, and constitutional symptoms. Unless in a high risk group (see below) no treatment is usually required.

Meningitis/Encephalitis
L. monocytogenes causes ~5–10% of all cases of community-acquired bacterial meningitis in adults in the United States. Case-fatality rates are reported to be 15–26%. This is usually a more sub-acute presentation with a predominance in chronically ill patients or at the extremes of age.
L. monocytogenes can directly invade the brain parenchyma, producing either cerebritis or focal abscess.

Infection in Pregnancy (Nothing makes an internist more uncomfortable than a pregnant patient - except maybe kids).
The usual presentation in pregnancy is a nonspecific acute or subacute febrile illness with myalgias, arthralgias, backache, and headache. Preterm delivery is a common complication. Prepartum treatment of bacteremic women enhances the chances of delivery of a healthy infant. Women usually do well after delivery: maternal deaths are very rare, even when the diagnosis is made late in pregnancy or postpartum. Overall mortality rates for fetuses infected in utero approach 50% in some series; among live-born neonates treated with antibiotics, mortality rates are much lower (~20%). Granulomatosis infantiseptica is an overwhelming listerial fetal infection a feared complication.

Treatment
High dose Ampicillin (2g q4h) or Pen G (4MU q4h) is the recommended therapy for serious Listeria infections. In penacillin allergic patients, desensitization is always an option, although good results have been demonstrated with Septra.

For more information, check out this review.

Hyponatremia

2010-05-18T08:56:00.004-04:00

Today we discussed hyponatremia and its management:

Some take home points - rapid correction of hyponatremia is often not required unless it is clear that the patient is acutely symptomatic from their hyponatremia - if you do need to give hypertonic saline (often in marathon runners, ecstasy overdose, etc.) it is often given as 3%NS with a 100cc bolus, then reassessment for further doses. The patient should be in a monitored setting and have frequent repeat electrolytes sent.

Consulting nephrology is never a bad idea for these patients.

We also discussed "BEER POTOMANIA" (apparently potomania is: An intense and persistent desire to drink alcohol to excess).

Malnourished patients (low-protein, high water intake diets) often do noy have enough solute excretion to deal with their water intake . Beer and other primary carbohydrates meals have little solute, however their CHO content suppresses endogenous protein catabolism/urea production.

Example:
Normal subject - 600 mosm/day of solute intake (and output). If they are hyponatremic and make a maximally dilute urine of 60 mosm/L (assume the kidneys cannot make a more dilute urine), their solute load allows a maximum of 10L of urine/day i.e. - their free H2O intake would have to exceed 10L for them to get more hyponatremic.

In malnourished patients - their solute intake/output can be 240 mosm/day. Therefore with a maximally dilute urine of 60 mosm/L (the kidneys cant make it more dilute) then their maximum urine output will be 4L/day. If their intake of fluid is >4L (>11 beers)/ day they will worsen their hyponatremia.

Other tips:
When seeing hyponatremia in the ER:

First rule out acute hyponatremia that needs acute correction.

Recheck the lytes if they were done several hours previously- the patient has possibly received intravenous fluids in the ER that may have significantly altered the sodium concentration - especially if the stimulus (often ECF volume depletion) for ADH secretion has been removed. Following the urine output may help to identify this (although recording can be an issue outside of the ICU) as a brisk, dilute diuresis can be bad sign.

Further tips from a nephrologist who attends on GIM are posted here, as well as an article about the use of DDAVP to prevent overly rapid sodium correction.

End of Life Care

2010-05-17T10:17:00.005-04:00

Many people have strong beliefs regarding feeding and end of life care. It is imperative to examine the goals of care with patients when making end of life care decisions and to remember that there will be a number of social, cultural and religious factors to be considered. Enlisting help from palliative care physicians, chaplaincy and other professionals with experience in helping make these decisions is often very important.

An article that examines some important points surrounding the use of feeding tubes in severe dementia is posted here. We often dont focus on promoting oral intake in hospital, but it is important to consider strategies to address this as well.

An article reviewing artificial nutrition and hydration at the end of life can be found here (Pub med abstract) or here (if logged through the university libraries)

COPD Physical Exam

2010-05-14T15:37:00.000-04:00

A summary of the physical exam for COPD is posted here

AECOPD

2010-05-11T09:07:00.002-04:00

Some interesting articles about morning report:

The Matrix article

The Pimping article

Points about COPD

Definition: (WHO)"Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases."

NOTE THAT COPD IS NOT AN ISOLATED LUNG DISEASE BUT HAS SYSTEMIC EFFECTS

Diagnosis: symptoms compatible with COPD, airflow obstruction (FEV1/FVC ratio less than 0.70 with no alternative cause.

Severity based on FEV1

Mild: FEV1 over 80% of predicted, with or without symptoms

Moderate COPD -FEV1 50-80% predicted

Severe COPD- FEV1 30-50%

Etiologies of exacerbations:

Majority are infection-related (80%) - H. Flu; S. Pneumo; M. Catarrhalis; P. Aeruginosa (5-10%); Rhinoviruses (20-25%).

15-20% are from other causes (inhaled irritants, air pollution)

Treatment consists of

1) Bronchodilators

2) Systemic steroids

3) ABx

4) Ventilatory support if needed (including BiPAP)

Abx - NOT needed for all exacerbations. Some advocate using only if increased sputum purulence. Classically used in all exacerbations requiring assisted ventilation (possible mortality benefit) or when there are 2 or more of increased dyspnea, sputum production or sputum purulence. One of the earlier papers to address that is referenced here.

Steroids: Trials have demonstrated benefit of systemic steroids for vs. placebo. No mortality benefit, but shorter length of stay, PFT improvement, and symptomatic improvement.

Original trial used Solumedrol 125mg IV q8h; no advantage to this high dose over Prednisone 40-60mg PO x 5-7d. No need for taper of this duration.

A NEJM paper from 2002 reviewing AECOPD is here

DKA/HONK

2010-05-10T09:45:00.002-04:00

A prior post on this topic with some good references is posted here

FUO

2010-05-10T09:35:00.003-04:00

The classic definition of FUO from the early 1960s was: fever greater than 38 degrees Celsius on several occasions over a 3 week period of time with week worth of hospital investigations. With changes in our healthcare system, it is now generally accepted that the definition applies if only 2-3 weeks have past and there have been initial investigations performed (the list of which tests varies)

When thinking about FUO remember the 4 major categories
Inflammatory, Infectious, Malignancy and up to 50% do not end up with a diagnosis (and generally have a good prognosis)

A prospective study from the Netherlands illustrates this

A proposed algorithm based on existing evidence was created by a Toronto internist and published in Archives of Internal Medicine. Dont forget that investigations should be tailored/expanded based on a comprehensive history and physical.