Clubbing

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A summary of the physical exam for COPD is posted here

AECOPD

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

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

FUO

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.

Today we discussed the antiphospolipid antibody syndrome and thromboembolic disease.

A NEJM images in clinical medicine case of phlegmasia cerulea dolens is posted here
Phlegmasia cerulea dolens:

• massive proximal DVT of the leg
  
• complications include severe pain , swelling, cyanosis, edema, venous gangrene, compartment syndrome, and arterial compromise, often followed by circulatory collapse and shock
• one of the few reasons to consider thrombolysis (genearlly catheter directed) or thrombectomy for lower limb DVT

APLA syndrome:

• Recurrent positive testing for an antiphospholipid antibody (>2x >3 months apart)
• Clinical sequlae - usually arterial and/or venous thrombosis or pregnancy loss (either recurrent early loss or single late loss, without other cause)
  

Notes on the lupus anticoagulant:

• causes prolonged aPTT (not always present), the dilute Russell viper venom time (dRVVT), the kaolin clotting time
• prolongation is not reversed during a 50:50 mix test
• patients with this dont always have SLE
  
• the term anticoagulant refers to invitro phenomenon - in vivo these patients are prone to thrombosis
  

Interstitial Lung Disease

A case of interstitial lung disease that covers alot of the issues discussed in morning report can be found here

Another article about exacerbations of IPF can be found here

From a public health point of view, an article about Canada's export of asbestos despite it being classified as a hazardous substance in Canada can be found here

FASTENS
The mnemonic for upper lobe intersitial pattern:
F - farmer's lung (hypersensitivity pneumonitis
A - Ank spond.
S - Sarcoid
T - TB
E - Eosinophilic Granulomatosis
N- Neurofibromatosis
S - silicosis

Sugar, sugar

We started today by discussing an approach to weight loss. A very useful classification is to divide causes with decreased appetite from those with increased appetite. Remember also the big categories: cancer, endocrine, psychological/psychiatric and access to food. CMAJ has a great review of weight loss in the elderly from our local experts.

We also touched on the criteria for Hyperosmolar Hyperglycemic State (calling in HONK is becoming passe). Though decreased level of consciousness is common (seen in over 50%) it is not always seen.

Finally we talked about the evidence for preventing --or delaying-- diabetes in persons with IGT/IFG. Check out the landmark Diabetes Prevention Program (DPP) study to learn more about it. The lifestyle modification arm showed a 60% reduction in progression to diabetes after 3 years, compared to a 30% reducation in those receiving metformin. Now if we could all just find the time to exercise....

Hypercalcemia

Some points about Hypercalcemia

Corrected Calcium:
The physiologically important calcium (Ca2+) is ionized calcium. This can be measured in the lab, however, total calcium is the value most commonly reported.

Calcium is bound to serum proteins, most importantly albumin. Therefore, in patients with low serum albumin concentration, the fraction of total serum Ca2+ that exists as ionized Ca2+ will be higher. When we are correcting calcium it is not because of a lab error, but rather to help us put the measured lab value into proper physiologic context in terms of possible causes, associated symptoms and need for treatment

It is important to know the serum albumin when interpreting total serum calcium levels. A correction for total serum calcium can be made using the following formula (alternatively ionized Ca2+ could be measured):

Ca = SerumCa + 0.02 * (NormalAlbumin - PatientAlbumin) (SI UNITS) - basically means that for every decrease of albumin by 10, add 0.2 to the total calcium.

Pseudohypercalcemia can occur when patients are hyperalbuminemic or have a multiple myeloma with a paraprotein that binds calcium (rare) - in these cases total CA2+ will be high, but ionized CA2+ will be normal.

DIFFERENTIAL DIAGNOSIS:
Most commonly either HyperPTH or Malignancy related. Malignancy related often presents with higher calcium levels, more symptoms and a more acute rise in calcium level (if previous values are known.
Other causes are out there - look them up if in doubt

Treatment:
TREATMENT
FLUIDS!!!!!!!!

Infusion rate depends on volume status, heart function, etc, but should target 100-150 cc urine output/hr - do not need to hydrate beyond euvolemia.

If severe/symptomatic consider: Bisphosphonates (IV) - will not take effect for 48-72 hrs, but will help maintain normal calcium when achieved.

Calcitonin - subQ is also very effective.

If hyperCa2+ is from sarcoid or lymphoma consider steroids (20-40 mg/day) - this works by decreasing calcitriol production from activated mononuclear cells in the lung and lymph nodes. Trying to get tissue before giving steroids if hypercalcemia not overly severe/symptomatic is a good idea.

AVOID LASIX since most patients are profoundly volume depleted initially and once replete can cause hypokalemia, hypomagnesemia, and lead to recurrence of volume depletion. A recent Annals of Internal Medicine article reviews the use/concerns regarding Lasix in hypercalcemia. If Lasix is need for pulmonary edema etc., it can certainly be given, just monitor lytes and volume status.

Dialysis should be considered if the above fail/can't be done because of renal failure or heart failure.

RENAL CELL CARCINOMA and PARANEOPLASTIC SYNDROMES

Hypercalcemia - from lytic bone mets, PTHrP or increased production of prostaglandins that promote bone resorption.

Polycythemia - from EPO overproduction

Hepaitc Dysfunction - "Stauffer syndrome" - in the abscence of mets, increased ALP (+/- fever, wt.loss, fatigue), often improves after nephrectomy

Fever, cacheixa

DKA and HONK

Prior Blog about the management of DKA can be found
here. Be sure to monitor closely both clinically and with charting of lab values.

Dont forget to look for the cause of DKA.
Prior blog about the common precipitants can be found here

Another point regarding phosphate:
Generally not recommended as may lower Ca and Mg levels. Replace if respiratory depression, cardiac dysfunction, hemolytic anemia or PO4 <0.32.

A CMAJ article about the management of diagnosis and treatment of HONK and DKA is posted here.

Another recent article on the issue can be found here.