Virchow's triad

---and his legacy. An interesting read.

Is it low T? Should you treat?

Here's a review from CCJM.

Administration of NAC for prevention of contrast nephropathy: what's the latest?

The evidence is mixed and weak and the guidelines (AHA/ACCF vs nephrology) are conflicting. Here's what the authors of a recent CCJM mini-review recommend:

Clarify whether contrast is truly needed

When possible, limit the volume of contrast, avoid repeated doses over a short time frame, and use an iso-osmolar or low-osmolar contrast agent

Discontinue nephrotoxic agents

Provide an evidence-based intravenous crystalloid regimen with isotonic sodium bicarbonate or saline

Although it is not strictly evidence-based, use NAC in patients with significant baseline renal dysfunction (glomerular filtration rate < 45 mL/min/1.73 m2), multiple concurrent risk factors such as hypotension, diabetes, preexisting kidney injury, or congestive heart failure that limits the use of intravenous fluids, or who need a high volume of contrast dye

Avoid using intravenous NAC, given its lack of benefit and risk of anaphylactoid reactions.

Sweet's syndrome

A couple of cases and a mini-review. 

ITP update

The topic is reviewed in a recent issue of CCJM.

Key points:

The old name for the disease, idiopathic thrombocytopenic purpura, is a misnomer. The disease is not idiopathic and most patients do not have purpura.

Though no longer idiopathic its pathogenesis is more complex than once thought. It is a disorder of both peripheral destruction and under production:

ITP is a complex immune process in which cellular and humoral immunity are involved in the destruction of platelets3 as well as impaired platelet production. Several theories have emerged in the last decade to explain this autoimmune process...

The triggering event for antibody initiation in ITP is unknown.3 Autoantibodies (mostly immunoglobulin G [IgG] but sometimes IgM and IgA) are produced against the platelet membrane glycoprotein GPIIb-IIIa. The antibody-coated platelets are rapidly cleared by the reticuloendothelial system in the spleen and liver, in a process mediated by Fc-receptor expression on macrophages and dendritic cells. Autoantibodies may also affect platelet production by inhibiting megakaryocyte maturation and inducing apoptosis.

The review had this updated information on the H pylori association:

The association between H pylori infection and ITP remains uncertain. Eradication of infection appears to completely correct ITP in some places where the prevalence of H pylori is high (eg, Italy and Japan) but not in the United States and Canada, where the prevalence is low.20 The different response may be due not only to the differences in prevalence, but to different H pylori genotypes: most H pylori strains in Japan express CagA, whereas the frequency of CagA-positive strains is much lower in western countries.

Treatment is summarized here.

Aldosterone receptor antagonists in heart failure management

Here is a superb update in CCJM. These things are clear:

The indications for the use of ARAs in heart failure are expanding since the publication of RALES.

ARAs are underutilized.

When they are used patients are not monitored well enough for hyperkalemia.

Myocardial infarction: an update on definition and classification

Do you know a type 1 from a type 4 MI? If not, read on.

ABI testing in the office

A CCJM review makes this strong statement:

The ankle-brachial index is valuable for screening for peripheral artery disease in patients at risk and for diagnosing the disease in patients who present with lower-extremity symptoms that suggest it. The ankle-brachial index also predicts the risk of cardiovascular events, cerebrovascular events, and even death from any cause. Few other tests provide as much diagnostic accuracy and prognostic information at such low cost and risk.

The use of novel anticoagulants in atrial fibrillation: superior to vitamin K antagonism in this meta-analysis

Note that the analysis included, in addition to dabigatran and rivaroxaban, two others not currently approved in the US.

Continuous infusion Zosyn (Pip/Tazo)

It makes pharmacodynamic sense, it is gaining in popularity and there is evidence that it is superior, but the evidence is low level. We need better clinical trials.

Should we skip SCIP?

One by one the core measures (now known by the feel-good term “value based purchasing”) are letting us down. Add SCIP to that list.

Short QT syndrome: what the hospitalist needs to know

CCJM has a nice nuts-and-bolts review. It contains new updates on the nuances of diagnosis and treatment. Simple reliance on the QT (or Qtc) is beset with difficulty, just as it is in the LQTS. I have blogged previously about SQTS here and here.

And remember, when it comes to the QT interval it's best to be average.

Hypersensitivity pneumonitis review

From the blue journal.

HP can present in many forms. Think of it in any patient presenting with interstitial lung disease.

Cognitive changes after survival of critical illness

This is now a well known entity. It was recently reviewed here in CCJM. Strategies for prevention remain controversial. Much attention has been devoted to sedation during mechanical ventilation in terms of dose, duration and choice of agent. And while these factors may impact the development of delirium it is not clear whether they affect the development of impaired cognition weeks and months after recovery. Regarding the choice of ventilator sedation agent the authors opine:

In our practice, we use dexmedetomidine as our first-line sedation therapy. In patients with hemodynamic instability, we use benzodiazepines. We reserve propofol for very short periods of intubation or for hemodynamically stable patients who cannot be sedated with dexmedetomidine.

Althma: part of the pro-inflammatory syndrome of obesity?

From the blue journal:

Objectives: We hypothesized that leptin levels would be increased in the bronchoalveolar lavage fluid from overweight/obese subjects and, furthermore, that leptin would alter the response of alveolar macrophages to bacterial LPS...

Measurements and Main Results: Leptin levels were increased in overweight/obese subjects, regardless of asthma status (P = 0.013), but were significantly higher in overweight/obese subjects with asthma. Observed levels of tumor necrosis factor-α were highest in overweight/obese subjects with asthma. Ex vivo studies of primary alveolar macrophages indicated that the response to LPS was most robust in alveolar macrophages from overweight/obese subjects with asthma and that preexposure to high-dose leptin enhanced the proinflammatory response. Leptin alone was sufficient to induce production of proinflammatory cytokines from macrophages derived from overweight/obese subjects with asthma.

Conclusions: Ex vivo studies indicate that alveolar macrophages derived from overweight/obese subjects with asthma are uniquely sensitive to leptin. This macrophage phenotype, in the context of higher levels of soluble leptin, may contribute to the pathogenesis of airway disease associated with obesity.

When your patient on pradaxa bleeds

---or has to have an invasive procedure: here is an update from Circulation.

Key topics...

Coag tests:
The aPTT is not very quantitative but can determine the presence or absence of drug effect. A normal value indicates absence of effect; a value greater than 2.5 x control 8-12 hours post dose indicates excess. The TT is also discussed in the article but is not in everyday clinical use.

Procedures:
Pradaxa need not be stopped for dental work, skin biopsy or cataract extraction but such procedures should ideally take place greater than 10 hours post dose.

For more invasive procedures it's a little more complicated:

For procedures associated with a moderate risk of bleeding, dabigatran should be held for 2 to 3 half-lives, whereas it should be held for 4 to 5 half-lives before procedures associated with a high risk of bleeding. Examples of procedures with a moderate risk of bleeding include pacemaker or implantable cardioverter-defibrillator implantation and colonoscopic resection of polyps, particularly those that are sessile and have a broad base. Procedures associated with a high risk of bleeding include urologic procedures, such as transurethral prostate resection, major abdominal or pelvic surgery for cancer, joint replacement surgery, cardiac surgery, and neurosurgery.

Here is an algorithm.

Also this:

If urgent surgery or intervention is required, the risk of bleeding must be weighed against the clinical need for the procedure. Ideally, surgery should be delayed for at least 1 half-life after the last dose of dabigatran or until the aPTT is normal or near normal. If the procedure is performed 2 to 4 hours after the last dose of dabigatran, the risk of bleeding is increased and strategies to reduce bleeding may be required.

Post procedure it can be restarted as soon as hemostasis is secured and bleeding risk is believed to be low, keeping in mind that unlike the case with warfarin the resumption of anticoagulant effect will be almost immediate.

The bleeding patient:
There is NO antidote although a neutralizing antibody is being developed (analogous to digibind?).

So you stop the drug, calculate the patient's creatinine clearance and, knowing that it has first order elimination kinetics you can do the math. For more severe, life threatening bleeding (e.g. head bleeds) that is not enough. It is removed pretty well by hemodialysis. Although there is no specific antidote currently available there has been talk of using 4 factor PCC (not available in the US), 3 factor PCC supplemented with a little recombinant activated factor VII or factor VIII inhibitor bypassing activity. Those remedies are mentioned in the review. The evidence to support their use is slim but an algorithm is presented.

The full text of the review is available at the link above.

Hereditary colon cancer syndromes

This review from CCJM covers clinical features including extracolonic tumors, classification, genetics, recognition and management.

Update on hypertrophic cardiomyopathy

Scientific advances in HCM have added much needed clarity to our understanding of the disease and its treatment approach. Here's an update in Circulation. Free full text.

Add CKD to the list of risk factors for VTE

---according to this large study.

Catheter directed treatment of PE

Reviewed in Circulation.