Precious bodily fluids honors William Stone

Bill Stone is another member of that dying breed of physician-scientists and master clinicians. He was a nephrology attending at the Nashville VA and Vanderbilt Hospital across the street when I was a medical student there. He had a superficial reputation for being a bit malignant but to those who knew him well he was a dedicated physician and teacher who cared greatly about the students and house staff. He was a walking encyclopedia of internal medicine. I was too intimidated to fully appreciate his teaching gifts.

Joel Topf at Precious Bodily Fluids has recently written a post in his honor which lists his 23 “rules of Stone” and mentions his research. Among many other things he discovered beta-2 microglobulin amyloidosis in hemodialysis patients.

Another of his research accomplishments impressed me as a med student. Back then IV penicillin G was used to treat a lot of serious infections. Every now and then patients with renal impairment would experience penicillin neurotoxicity and seize. Thus was born the notion that doses of pcn that were appropriate for normal renal function were “comparably massive” in patients with renal failure. Stone and one of the ID fellows got together, looked at the pharmacokinetics and worked out a method for “renal dosing” of pcn.

Of his 23 rules I like #18: “If an older doctor writes an axiom or a diagram on a piece of paper, ask if you can have it.” (Now some EBM apologists who decry experience and expertise as a basis for learning won't like this).

Sometimes I feel a little worn down by the legal and administrative baggage I face in practice. Reflecting on the legacy of the exemplars of internal medicine is therapy for me.

The asthma-COPD overlap syndrome

ACOS, reviewed here. From the review:

ACOS accounts for approximately 15–25% of the obstructive airway diseases and patients experience worse outcomes compared with asthma or COPD alone. Patients with ACOS have the combined risk factors of smoking and atopy, are generally younger than patients with COPD and experience acute exacerbations with higher frequency and greater severity than lone COPD.

It is not yet a well defined clinical entity, but is a useful construct.

Safe drug use in long QT and Brugada syndromes

A review of two popular websites with links.

Patent foramen ovale in patients with obstructive sleep apnea

According to this study it is common in patients with OSA and its coexistence is associated with more profound nocturnal desaturation. In the small number of patients in the study, closure did not help.

The fragmented QRS

It indicates myocardial scar no matter what the underlying cardiac disease.

I first blogged it several years ago and the field has since seen further clarification as documented in this review.

FFR guided PCI: does it really matter?

We know it makes sense physiologically but does it make a difference in outcomes? A recent study suggests it does.

D-dimer testing and aortic dissection

How useful is it to exclude the diagnosis?

According to one recent review:

The sensitivty of D-dimer test for AD diagnosis is reported as close to 100% in the literature and has a negative predictive value between 92% and 100% [5, 6]. Two meta-analyses confirmed that D-dimer testing is useful for the diagnosis of suspected acute aortic dissection [2, 3].

Additional references here and here.

D-dimer testing combined with the ADD score might be a useful approach.

Novel oral anticoagulants for stroke prevention in a fib in the elderly

Practical aspects are reviewed here. Free full text available.

More on breath acetone (BA) in heart failure

Via Medpage Today.

Baseline BA values vary widely (many fold) in normal subjects. So, comparison with a patient's baseline may be more useful than the absolute value.

In this study a mass-spectrometry technique was used but simple gas chromatography also works.

This field is very promising. I previously blogged the topic and provided background here.

Hypomagnesemia due to PPI use

It's not always benign. A mini-review accompanies this case report. Hypokalemia and hypocalcemia are frequent accompaniments via mechanisms mentioned in the paper.

Emergency Medicine board review

Free, open access. It would be nice if they had something like this for IM or hospital medicine.

The acute porphyrias

A review.

The National Quality Forum endorses early goal directed therapy

---and it took them, what, 12 years?

Via MDLinx.

The patient has right ventricular tachycardia (LBBB morphology)---is it idiopathic or ARVD?

A simple scoring algorithm can discriminate.

Transthyretin amyloidosis: an under appreciated entity

From the review:

Transthyretin (TTR) amyloidosis is a systemic disorder characterized by the extracellular deposition of amyloid fibrils composed of TTR, a plasma transport protein for thyroxine and vitamin A that is produced predominantly by the liver. TTR can dissociate from its native tetramer form, then misfold and aggregate into amyloid fibrils that accumulate in various organs and tissues, causing progressive dysfunction. TTR amyloidosis is the most common form of hereditary (familial) amyloidosis, and is caused by mutations that destabilize the TTR protein. TTR amyloidosis also encompasses an age-related amyloidosis known as senile systemic amyloidosis, an acquired disorder mainly affecting men after the age of 60 years, that results from the deposition of wild-type TTR amyloid.

Statin-diabetes association: what’s the skinny?

From a recent review in CCJM:

The evidence from individual clinical trials is mixed, but meta-analyses indicate that statin therapy is associated with approximately a 9% higher risk of diabetes (an absolute difference of about 0.4%).

We need to interpret this information cautiously. Many potentially confounding factors are involved, and rigorous prospective trials are needed to examine this issue.

The benefit of preventing serious cardiovascular events seems to outweigh the higher risks of diabetes and poorer glycemic control, and we should continue to give statins to patients at moderate to high risk, including those with diabetes, with vigilance for these side effects.

New oral anticoagulants for prevention and treatment of VTE

The topic is nicely reviewed here. Of greatest interest is rivaroxaban (Xarelto) as it is the only one among the novel oral anticoagulants approved for treatment of DVT and PE in the US. Although the review summarizes the usual pharmacology and labeling a nagging question concerning rivaroxaban remains: is it time to change practice and if so, how? Now when patients present with DVT or PE do we just give them a pill and call it a day?

That question warrants a close look at the EINSTEIN trials for DVT and PE. In both trials, patients in the rivaroxaban arm were usually pretreated with enoxaparin for a day or two prior to enrollment. So the question of treatment in the first 24 hours or so is not well studied. Second, patients in both trials were excluded if thrombolytic therapy was anticipated, whatever that meant. But it implies that the treatments have not been compared in the sickest of the sick patients. Remember too that the results show non-inferiority rather than superiority to standard treatment. Finally, there are all those pesky post-marketing reports that are sure to follow.

So putting aside for now cost and patient preference considerations what's a hospitalist to do? If you're prone to err on the side of caution you might want to go with the time tested regimens for at least the first 24 hours, particularly in the sicker patients.

I did look this up in UptoDate. At present, acknowledging that this may change, they are recommending traditional treatments (LWMH or UFH followed by VKA) over novel anticoatulants, for the entire treatment course due to more clinical experience with the former.

Discussions about NCCAM's chelation study (TACT)

Cardiobrief has posted an update. What amazes me about these discussions is that anyone would take TACT for more than entertainment value. Equally amazing is that JAMA, which is supposed to be a top level journal, would give it the time of day. (Would they loosen their standards in kind for Pharma sponsored trials? Don't think so). The irony is that what some would consider a lower tier journal, the Medscape Journal of Medicine, had the most scientifically rigorous perspective on the trial. (See also here).

At least JAMA did publish one appropriately critical editorial---that of Steven E. Nissen, MD. In it Nissen echoed precisely a concern I expressed several years ago in my Magical Mystery Tour of the TACT study sites when he said:

Execution of a high-quality RCT requires skilled investigators and study coordinators who understand these critical scientific principles. For TACT, more than 60% of patients were randomized at enrolling centers described as complementary and alternative medicine sites. Many of these centers have websites that describe their services, which include an array of unproven therapies ranging from stem cell therapy to regrow breasts after mastectomy, high-dose intravenous vitamin C to treat cancer, and use of cinnamon for treating diabetes to treatment of influenza with antimicrobial essential oils or homeopathic remedies (while warning patients not to undergo immunization). Other sites offer chelation to treat or cure a variety of conditions including autism in children. A common theme of these centers is evident—they appear to attempt to appeal to vulnerable patients who have challenging diseases by offering a variety of unscientific and unproven therapies. Whether a high-quality RCT can be performed at such sites is questionable.

A missing element in most of these discussions is whether, before TACT was even conceived, chelation therapy as a remedy for atherosclerotic disease even deserved further study. It didn't.

Finally, the author or the Cardiobrief piece gave this little shout out to Orac:

The most sustained assault on TACT, and on Krumholz’s position, comes from the highly-regarded skeptic blog Respectful Insolence written by Orac (the pseudonym of David Gorski, a surgical oncologist). In his take-no-prisoners assault on TACT, JAMA, and Krumholz, Orac writes “that JAMA is every bit as guilty as The Lancet was in 1998 when it published Andrew Wakefield’s antivaccine nonsense…. If published at all, TACT should have been published in some crappy, bottom-feeding journal, because that’s all that it deserves.”

Inverted takotsubo cardiomyopathy

In an increasing number of reported cases of stress induced cardiomyopathy, as illustrated in this report, it's the base of the heart rather than the apex that balloons. Although sometimes termed inverted takotsubo cardiomyopathy the left ventriculogram, in contrast to typical cases of apical ballooning, does not resemble a Japanese octopus trap. The entire spectrum might better be termed “stress cardiomyopathy.”

CT pulmonary angiography and the over diagnosis of pulmonary embolism

A recent article in the Texas Heart Institute Journal by Dr. Herb Fred includes this statement:

In the teaching hospital where I work, “fishing” is rampant. By fishing, I mean scanning the body part thought to be the source of the patient's complaint or problem, hoping thereby to reel in some sort of diagnosis.48 In these cases, the physician essentially bypasses the history and physical examination and, guided solely by the patient's chief complaint, proceeds directly to CT scanning with no particular pre-test diagnosis foremost in mind. This sport typically takes place in the emergency department, where almost all patients entering with chest pain (not further described) or shortness of breath (not further defined) promptly undergo contrast-enhanced chest CT. It should be obvious, however, that such robotic, indiscriminate, and unduly expensive screening is bound to uncover pulmonary arterial filling defects every now and then. And it does. The defects occasionally appear in the main or lobar arteries, but most of the time they appear in just 1 or 2 segmental or subsegmental branches—areas where reconstruction artifacts or contrast-streaming can produce a false-positive interpretation. Nevertheless, once these defects are detected, all thinking stops, pulmonary embolism becomes the primary diagnosis, and anticoagulation automatically ensues.

But should it, necessarily? That question, as addressed in this paper, gets a little complicated and it deals with two different situations: 1) pulmonary artery filling defects discovered incidentally when chest CT scanning was done for non cardiovascular indications and 2) filling defects (“positive” study) seen when scanning is done in knee jerk fashion to patients with chest pain without prior careful examination or thought.

It is unclear in many such cases whether anticoagulation is necessary, particularly if the filling defects are subsegmental and isolated.

So one may end up dealing with a situation in which thinking which should have taken place before imaging is considered has to be done after the patient “rules in” for PE. That inevitably leads to more testing, for confirmation and to assess risk coupled with clinical judgment applied better late than never.

Vocal cord dysfunction

An asthma mimic.

Atrial appendage exclusion for stroke prevention in atrial fibrillation: is it ready for prime time?

Here's the current status.

Acute kidney injury (AKI)

Lots of good stuff in this review.

Some take home points:

The cornerstone of assessment and management is volume.

Assess volume and volume responsiveness (which can be a little tricky, and how you do that depends on the resources where you practice) and replete as indicated.

Low FeNa does not always mean volume responsive. Exceptions are listed and discussed.

Though aggressive volume resuscitation is indicated in early septic shock and often early AKI a price is often paid later in terms of organ congestion (lungs, kidneys, skin, abdominal compartment) such that less may be more in the later stages.

Diuretics have not been proven to lead to improvement in hard clinical outcomes although there may be some benefit in mitigating volume overload and hyperkalemia in those patients capable of responding.

Atrial fibrillation in young and old patients

A review.

Lectures in pulmonary pathophysiology

From UCSD.

Insulin resistance syndromes

This review is one of the best discussions I've seen on the various insulin resistance syndromes. It centers around a case report of a patient with type 2 DM who developed DKA and extreme insulin resistance in the face of acute MI.

The case in question raises several discussion points. This is a case of DKA which, in defiance of the usual rule, developed in a patient with DM type 2. Traditional teaching holds that DKA is associated with DM 1. DM 1 strictly defined, however, is that type of DM in which DKA predictably develops spontaneously, in deprivation of administered insulin, in the basal state. This patient had acute MI and was therefore not in a basal state. But to further complicate matters this patient, being Hispanic, could have had ketosis prone type 2 diabetes, a syndrome in which patients seemingly flip-flop between type 1 and type 2 phenotypes. This is a condition of intermittent beta cell fatigue which may have rendered the patient more prone to glucose toxicity which the authors speculate was a factor. This patient's insulin resistance was not defined by the presence of DKA but rather by the amount of administered insulin it took to achieve glycemic control.

The activation of counter regulatory (stress) hormones by the AMI, and perhaps inflammatory cytokines, could explain the development of DKA but, in the opinion of the authors, probably not this degree of insulin resistance (extreme insulin resistance). While AMI has been cited as a situation causing extreme insulin resistance, it appears to do so by multiple and poorly understood mechanisms.

Bell's palsy

Quick reference via Academic Life in Emergency Medicine.

Coffitivity gets the creative juices flowing

Atmosphere for the blogging cave!

HT to Academic Life in Emergency Medicine.

Precedex for ethanol withdrawal??

Here's a nice reference.

A few observations:

It is supported only by low level evidence.

It is off label.

It appears to be safe and is gaining popularity.

It harks back to the old trick of adjunctive use of clonidine (it's a central alpha2 agonist).

It is physiologically very appealing in those patients with hypertension and tachycardia.

Medicine and basic science videos

Browse here. 

Lytics for submassive PE: Is the controversy any closer to being resolved?

No, despite two recently completed trials, one recently published and one just presented in abstract form at ACC.  The former study, published in the American Journal of Cardiology, using half dose TPA, showed good safety (no major bleeding) but improvement in only soft endpoints attributable to TPA.  The study presented at ACC showed improvement mainly in soft endpoints and a concerning increase in major bleeding attributable to thrombolysis.  So read the studies and opine as you will but my bottom line remains that thrombolysis for submassive PE is not well supported.

There is a nice summary on this topic over at Academic Life in Emergency Medicine.

Professor Fink's lectures

In physiology and other topics.

Human physiology lectures

Slide sets.

Mastocytosis: cutaneous and systemic

A review.  Multiple variants of the disease exist and the protean manifestations can be attributed to the vast array of mediators secreted from the mast cell.

Video lecture on blood gas analysis in critical care

FDA clarifies the mechanism of cardiovascular death associated with azithromycin

It can prolong the QT and lead to Torsades.  The original report linking it to cardiovascular death was in NEJM last year.

We can add it to the list of antibiotics capable of doing this.

Is pacing effective in vasovagal syncope?

It's no cure but it has a role and patient selection is important.  The pendulum has swung back and forth on this topic.  The Vasovagal Pacemaker Study of some years ago failed to show a benefit when patient selection was based on tilt testing.  But an abstract just presented at ACC showed benefit after careful patient selection based on evaluation via an implanted event monitor.

Is it the end of the line for niacin?

No, but a new study presented at ACC raises concerns.  Before jumping to conclusions about niacin note the following:

The results do not permit a distinction between niacin and the antiflushing agent laropiprant in attribution of the negative outcomes.

The patients were studied without regard to LDL particle density, ignoring previous findings that niacin has a powerful niche in patients with low LDL particle density (LDL pattern B).

In the trial, niacin was combined with a statin with a higher toxicity profile.

In the Coronary Drug Project, an example of comparative effectiveness research done decades before the term was co-opted for political ends, niacin was the first lipid modifying agent found to favorably impact significant clinical outcomes.

Respiratory physiology lectures

From UCSD.

I love posting these educational resources.  Remember a couple of RW's rules for learning:  The better you understand physiology the less stuff you'll have to memorize (or look up) AND the quickest way to get smart is to realize you're a dumb s...

Learners TV

For lectures on just about everything.  Lots of basic science and medical stuff.  

Aldosterone receptor antagonism (Inspra) in the first 24 hours of STEMI?

Benefit was shown in a trial presented at ACC but the composite endpoint was driven mainly by a surrogate marker (BNP/proBNP).   So....hypothesis generating and not ready for prime time pending further study.  Via Medpage Today.

Physiochemical analysis and strong ion difference: another method of acid-base analysis

Not for sissies. Watch this when you're well rested and well fed.

Questionable treatment shamefully promoted

---at respected national meetings.  The trial in question (TACT) was hopelessly flawed in my opinion and that of others.  

Spironolactone in diastolic heart failure

Pathophysiologic rationale and surrogate endpoints look promising but that's as far as we've come so far.  A long journey awaits.  The latest study in JAMA.

RW's Tweets

OK, so I've stepped into the 21st century and am finally tweeting.  But I need some followers.

Medical education resources on YouTube

Here are some I've found recently:

COMLEX USMLE review.

Medical Sciences Animated Videos.

Eric's Medical Lectures.

MedCram.

The Southern diet as a risk factor for stroke

Presented at the International Stroke Conference.

Via Medpage Today.

Initial sedation intensity in mechanically ventilated patients: go easy

From this study recently published in the blue journal:

Measurements and Main Results: We studied 251 patients (mean age, 61.7 ± 15.9 yr; mean Acute Physiology and Chronic Health Evaluation [APACHE] II score, 20.8 ± 7.8), with 21.1% (53) hospital and 25.8% (64) 180-day mortality. Over 2,678 study days, we completed 14,736 RASS assessments. Deep sedation occurred in 191 (76.1%) patients within 4 hours of commencing ventilation and in 171 (68%) patients at 48 hours. Delirium occurred in 111 (50.7%) patients with median (interquartile range) duration of 2 (1–4) days. After adjusting for diagnosis, age, sex, APACHE II, operative, elective, hospital type, early use of vasopressors, and dialysis, early deep sedation was an independent predictor of time to extubation (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87–0.94; P less than 0.001), hospital death (HR, 1.11; 95% CI, 1.02–1.20; P = 0.01), and 180-day mortality (HR, 1.08; 95% CI, 1.01–1.16; P = 0.026) but not delirium occurring after 48 hours (P = 0.19).

Conclusions: Early sedation depth independently predicts delayed extubation and increased mortality, making it a potential target for interventional studies.

Which antidepressants prolong the QT interval?

According to a BMJ study:

Results Dose-response association with QTc prolongation was identified for citalopram (adjusted beta 0.10 (SE 0.04), P less than 0.01), escitalopram (adjusted beta 0.58 (0.15), P less than 0.001), and amitriptyline (adjusted beta 0.11 (0.03), P less than 0.001), but not for other antidepressants examined. An association with QTc shortening was identified for bupropion (adjusted beta 0.02 (0.01) P less than 0.05). Within-subject paired observations supported the QTc prolonging effect of citalopram (10 mg to 20 mg, mean QTc increase 7.8 (SE 3.6) ms, adjusted P less than 0.05; and 20 mg to 40 mg, mean QTc increase 10.3 (4.0) ms, adjusted P less than 0.01).

Obesity associated severe asthma

Obesity may be associated with a distinct phenotype of severe asthma according to this paper.

Prehospital advanced airway management associated with more than double the risk of bad neurological outcome

----in this analysis.

This adds support for the arguments Gordon Ewy and his group at Arizona have been making for years, as I have posted here many times.

In which I ponder the antecedents of quackademic medicine

For some time now bloggers who share a concern about quackademic medicine (a term referring to the pervasive infiltration of quackery into the curricula of American medical schools which I coined here) have pondered the reasons. Indeed the reasons are multiple and complex. But I believe there is a causal chain and if you trace back far enough along the chain you land here: the American Medical Student Association (AMSA).

In the past I’ve blogged a great deal about their woo promoting agenda. Moreover, in considering this agenda alongside AMSA’s PharmFree initiative I have previously noted, in less PC terms, a certain lack of internal consistency.

But over time my enthusiasm for calling out the quack promoting activities of the AMSA waned; despite multiple attempts of myself and others in the blogosphere to raise awareness the problem continued unabated. Among the many folks in high places in the world of medical education few people seemed concerned enough to do anything to try and stem the tide.

I recently ran across two wonderful blog posts (here and here) that rekindled my interest. These bloggers have succeeded in probing the extensive AMSA site and unpacking the woo promoting content better than I ever did. Both posts are worth the read. Great exposure!

Denver cluster of carbapenem resistant Klebsiella

Via Medpage Today.

The isolates produced the New Delhi metallo-beta-lactamase (NDM) gene...

Breath acetone as a biomarker in heart failure

It performed comparably to BNP/proBNP in this study, both in diagnosis and severity assessment.

The incredible and never adequately explored potential of breath acetone (BA) analysis for clinical application has long been a pet interest of mine. As a medical student I got to spend my summers playing with the gas chromatograph machine in Oscar B. Crofford's lab. Although the focus of that research was diabetes and obesity BA has potential application as a biomarker in a variety of disease states. This is best appreciated by understanding that BA reflects lipolytic activity; it is, as Dr. Crofford was fond of saying, the “smoke of burning fat.” That in turn reflects the balance between insulin and counter regulatory hormone activity on hormone sensitive lipase located in adipose tissue cells. The counter regulatory hormones are the stress hormones: epinephrine, norepinephrine, growth hormone, glucagon and cortisol. So elevated BA reflects the catabolic state and/or the ratio of activities of stress hormones to insulin.

The methodology is simple, specimen collection is easy (the patient can exhale into a syringe) and turn around is instantaneous. BA analysis deserves further study in a variety of clinical situations.

HIV disease as a powerful risk factor for lung cancer

A recent commentary in Chest notes a marked increased risk. Age of onset and tobacco burden are much lower than in the general population and presentation with advanced disease is common. Histologic type is similar to the general population.

ICU delirium

Here's a nice review and it's free full text.

Nonpharmacologic modalities are preferred by far over drugs though the latter are popular and sometimes necessary when the delirium is agitated. Data to support the use of drugs are sparse. Antipsychotics tend to be preferred over benzos except for alcohol withdrawal delirium, in which benzo therapy is the treatment of choice and antipsychotics are avoided. There is little to recommend second generation over older (e.g. haldol) agents. Dexmedetomidine has promise and is popular, but evidence in favor of its use is weak.

Extreme hypertriglyceridemia

Extreme hypertriglyceridemia can cause acute pancreatitis. It can also wreak havoc on the management of hospitalized patients by interfering with their lab tests. Management is a challenge, as it often responds inadequately to conventional measures. This article discusses two under appreciated (and off label) tricks of the trade: insulin infusion and heparin infusion. These treatments rapidly clear triglycerides and work about as well as plasmapheresis. They work by facilitating lipoprotein lipase. In the case of insulin, hark back to basic biochem and note an important distinction which is an apparent paradox: while insulin facilitates the action of lipoprotein lipase to clear triglycerides from the circulation it also inhibits hormone sensitive lipase in adipose tissue, the rate limiting enzyme for lipolysis and one of the two on-off switches for ketosis.

Obstructive sleep apnea, stroke and dementia

Under appreciated associations.

Lactate clearance predicts mortality

In severe sepsis.

Cardiac amyloidosis

The best review of cardiac amyloidosis this blogger has seen.

ACEI/ARB plus diuretic plus NSAID: the renal triple threat

----for AKI, as reported in BMJ and summarized here. Then again I worry about the renal risk from NSAIDs whether or not they are combined with other drugs.

Endovascular repair of abdominal aortic aneurysm: where we've come in 20 years

Now, more endo repairs have been done than open repairs. Over 70% of repairs now are endo repairs. The history and current status of the procedure are discussed in this review.

Continuous beta lactam infusion

It seems to work better. This harks back to the old days of using continuous infusion IV PEN G to treat meningitis.

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.

Should we artificially lower temperature in septic patients? It's complicated.

In general the lowering of body temperature in febrile patients via antipyretics or external methods is useless in terms of outcomes and may be harmful. Exceptions include heat stroke and other hyperthermia syndromes, stroke patients and post cardiac arrest patients.

The issue recently became more nuanced when publication of this paper from the blue journal added another possible exception: patients in septic shock treated with external cooling, in whom a decrease in pressor requirements and mortality was observed. On the other hand the use of antipyretics in septic patients across the board was associated with increased mortality in this study.

It is intuitive that external cooling would reduce pressor requirement because it induces vasoconstriction.

Influenza resources

Here's the link for professionals from the CDC and the CCJM annual update.

Asthmatic granulomatosis: a novel phenotype of severe asthma

What has come to be known as severe asthma comprises a number of unique phenotypes, poorly understood. A novel phenotype characterized by granulomatous inflammation is described in this paper from the blue journal.

Apheresis and plasma exchange: what the hospitalist needs to know

How it's done, how it works, when to do it.

Subclinical hyper- and hypothoroidism increase the risk for heart failure events

----according to the findings in this pooled analysis.

Peripartum cardiomyopathy

This topic was nicely reviewed in the Texas Heart Institute Journal and the free full text can be accessed here.

Key points:

Its onset can be in late pregnancy or up to 5 months postpartum.

Diagnosis is by exclusion of other heart disease combined with, in order to avoid overdiagnosis, very specific echocardiographic criteria.

Treatment includes general heart failure therapy (a table in the article summarizes drug precautions during pregnancy and lactation) and disease specific therapies.

Recovery is frequent but not invariable.

Neurogenic pulmonary edema

Some lessons in neuropulmonology from the journal Critical Care:

A common thread among all case descriptions of NPE is the severity and acuity of the precipitating CNS event. Neurologic conditions that cause abrupt, rapid, and extreme elevation in intracranial pressure (ICP) appear to be at greatest risk of being associated with NPE..

The autonomic nervous system and catecholamines play a significant role.

Annoying habits in the medical record

Here are some of Dr. Herb Fred's pet peeves. A couple of my favorites:

Many consultants from various disciplines routinely end their reports with, “Thank you for allowing me to participate in the care of this most interesting patient.” What is the difference between an uninteresting patient, an interesting patient, and a most interesting patient?7 The answer, like beauty, lies in the eyes of the beholder. In my eyes, all patients are interesting, but not all doctors are interested.8 A simple “Thank you” or “Thank you for this consultation” would be sufficient and devoid of insincerity and cliché.

Finally, “The patient is ‘satting’ at 88%.” This expression of the patient's oxygen saturation level crops up frequently, not only in hospital records, but also in Morning Report, teaching rounds, and doctors' lounges. Patients can sit or be sitting, but they can't sat or be satting. To sat is not a verb form. It's a neologism—arguably the most popular neologism in medicine today. House officers are particularly fond of it, uniformly include it in case presentations, and consider it the 5th vital sign.9 Unless teaching faculties consistently prohibit its use by all trainees, “satting” will continue to saturate the medical environment.

I would add that those fond of the term “satting” are not only grammatically incorrect but also tend to be confused about the physiology of oxygen transport.

Dr. Fred opens:

This editorial focuses on selected examples of bad habits that I have found repeatedly in traditional (paper) hospital records.

Well, Dr. Fred, it only gets worse in the electronic medical record.

The EMR and diabetes care: no impact

This study is important because it looked not just at the phony surrogate of performance but also at outcomes. The EMR was no better than paper in either category. HT to Clinical Cases and Images.

Dr. Smith talks about his ECG blog

With the passage of the old generation of electrocardiography masters (Marriott, Hurst) a new generation of ECG masters is arising and it comes from the ranks of emergency medicine. The driving force behind this is the fact that early “STEMI” recognition, both in the ED and in “the field,” is a performance measure. No one wants to miss one and no one wants egg on their face for calling a STEMI false alarm. Emergency medicine types are motivated more than ever to get it right.

Dr. Smith teaches residents in emergency medicine. His blog is on my list of the best ECG resources on the web.

Via Clinical Cases and Images.

Doctors on the receiving end of abuse

Sometimes it's patient against doctor, sometimes it's doctor against doctor. This paper is not quantitative but it has a ring of truth.

Cardiac device associated infections

Here's a nice little article in the Texas Heart Institute Journal.

Key points:

Presenting findings may be nonspecific and subtle. It may show up late after implantation. System explantation is generally recommended.

Drink coffee, cut your nasal MRSA carriage rate in half

Hospital administrators takenote---don't skimp on the coffee machines.

Cellulitis and its mimics

This review deals with several non-infectious mimics. Presentations of cellulitis which harbor more serious conditions such as nec fash, abscess or bad fungal infections were not covered.

Cardiac device therapy: ICD and CRT

A comprehensive review in the Texas Heart Institute Journal covers standard indications (ischemic and non-ischemic cardiomyopathy), unusual indications (infiltrative diseases, channelopathies) and controversies (timing of implantation after MI or onset of HF). Free full text available here.

Yet another CAM promoting article in a mainstream medical journal

The premise of this article seems to be that treatment choices should be based on perception and preference. What ever happened to evidence and scientific plausibility?

A review of acute aortic regurgitation

Free full text from Circulation.

Key points:

Acute severe AR may be difficult to recognize clinically and is often erroneously diagnosed as another acute condition such as sepsis, pneumonia, or nonvalvular heart disease.

Infective endocarditis and aortic dissection are the “big two” causes and their managements are depicted in this figure.