Eosinophilic esophagitis: clinical features

From a recent review article:

Eosinophilic esophagitis (EoE) may affect humans at any age with a predominance for Caucasian males... In adolescents and adults, dysphagia and food impactation become the predominant symtoms. EoE should also be considered in cases of refractory heartburn in both children and adults. Concomitant allergic diseases such as asthma, rhinitis and eczema, as well as peripheral eosinophilia and elevated total serum IgE values are common in pediatric and adult EoE patients. EoE seems to be primarily a food antigen–driven disease, whereas in adults, aeroallergen sensitization may dominate. Endoscopic features of EoE include mucosal edema, furrows, exudates, corrugated rings, strictures, and the so-called crepe paper sign. There appears to be a shift from an inflammtory-predominant phenotype in young childhood towards a more fibrotic phenotype in adolescents and adults. Long-term follow studies suggest that EoE is a chronic and protentially progessive disease causing recurring dysphagia in the majority of cases. The prevalence of strictures significantly increases with the duration of untreated disease..

A field guide to ECG lead misplacement

The electrocardiographic patterns produced by ECG lead misplacement are summarized in this paper.

Chest lead misplacement is pretty easy to spot. The most common limb lead misplacement is reversal of the arm electrodes. This pattern is well known and often picked up by computerized ECG analysis. Other limb lead misplacement patterns can be more tricky. Here is a summary of the more common ones:

Arm electrode reversal

Lead I is inverted.

Arm electrodes reversed with leg electrodes

Lead I is isoelectric. (This illustrates the principal that whenever you see electrical silence in a bipolar limb lead, it means both of that lead's electrodes are connected to the legs. It reflects the fact that there is no potential difference between the legs).

Right arm right leg reversal

II is isoelectric for the same reason as above.

Left arm right leg reversal

III is isoelectric.

The authors conclude:

A summary of the footprints of ECG lead malposition should be readily available for those who perform ECGs, those who interpret the tracings and those responsible for clinical care.

Well, here you have it. Much more detail is contained in the full text.

ECCO2R in patients with COPD

From a recent review:

We identified 3123 citations. Ten studies (87 patients), primarily case series, met inclusion criteria. ECCO2R prevented intubation in 65/70 (93 %) patients and assisted in the successful extubation of 9/17 (53 %) mechanically ventilated subjects. One case–control study matching to noninvasively ventilated controls reported lower intubation rates and hospital mortality with ECCO2R that trended toward significance. Physiological data comparing pre- to post-ECCO2R changes suggest improvements for pH (0.07–0.15 higher), PaCO2 (25 mmHg lower), and respiratory rate (7 breaths/min lower), but not PaO2/FiO2. Studies reported 11 major (eight bleeds requiring blood transfusion of 2 units, and three line-related complications, including one death related to retroperitoneal bleeding) and 30 minor complications (13 bleeds, five related to anticoagulation, and nine clotting-related device malfunctions resulting in two emergent intubations).

Conclusion

The technique is still experimental and no randomized trial is available. Recognizing selection bias associated with case series, there still appears to be potential for benefit of ECCO2R in patients with COPD exacerbations. However, it is associated with frequent and potentially severe complications. Higher-quality studies are required to better elucidate this risk–benefit balance.

Perspective and common sense in managing type 2 diabetes in older individuals

A recent JAMA paper reviewed this topic. From the abstract:

Four large randomized clinical trials (RCTs), ranging in size from 1791 to 11 440 patients, provide the majority of the evidence used to guide diabetes therapy. Most RCTs of intensive vs standard glycemic control excluded adults older than 80 years, used surrogate end points to evaluate microvascular outcomes and provided limited data on which subgroups are most likely to benefit or be harmed by specific therapies. Available data from randomized clinical trials suggest that intensive glycemic control does not reduce major macrovascular events in older adults for at least 10 years. Furthermore, intensive glycemic control does not lead to improved patient-centered microvascular outcomes for at least 8 years.

The surrogate endpoints for microvascular disease are things like findings of retinopathy or laboratory evidence of renal involvement. This was the basis for a shrill body of opinion following the release of the UKPDS findings that intensive glycemic control in DM 2 was not effective because the improved endpoints were not “outcomes that mattered” (eg blindness or ESRD resulting in the need for chronic dialysis). I've come to consider statements like that as anti-EBM because under first EBM principles it is the patient who decides what outcomes matter, not someone else from afar. As the JAMA paper authors acknowledge, the surrogate nature of the outcomes lasts about 8 years. Longer term follow up of the UKPDS suggested differences in more robust clinical endpoints. In patient-centered decision making a lot depends on the patient's expected longevity.

The paper goes on:

Data from randomized clinical trials consistently suggest that intensive glycemic control immediately increases the risk of severe hypoglycemia 1.5- to 3-fold. Based on these data and observational studies, for the majority of adults older than 65 years, the harms associated with a hemoglobin A1c (HbA1c) target lower than 7.5% or higher than 9% are likely to outweigh the benefits.

So according to these authors the optimal range for many patients in an internist's practice is an A1c level between 7.5 and 9. That bold statement runs counter to a lot of prevailing diabetes dogma. But the harm associated with intensive glycemic control is more than hypoglycemia. For although intensive control does without question confer microvascular benefit, it also seems to result (with a few particular exceptions) in macrovascular harm. See here.

More from the article:

However, the optimal target depends on patient factors, medications used to reach the target, life expectancy, and patient preferences about treatment. If only medications with low treatment burden and hypoglycemia risk (such as metformin) are required, a lower HbA1c target may be appropriate.

Again, it goes beyond hypoglycemia. Metformin is one of only two diabetes drugs found to confer macrovascular benefit and it is likely a pleiotropic effect, having little if anything to do with blood sugar. It would also be reasonable to say that nonpharmacologic modalities (diet, exercise) would confer benefits across the range of A1c.

The article concludes:

High-quality evidence about glycemic treatment in older adults is lacking. Optimal decisions need to be made collaboratively with patients, incorporating the likelihood of benefits and harms and patient preferences about treatment and treatment burden. For the majority of older adults, an HbA1c target between 7.5% and 9% will maximize benefits and minimize harms.

In discussions of diabetes we have, ever since DCCT and the advent of home glucometers and A1c, developed an obsession with glucose lowering. Diabetes, however, is multifaceted and there is much more to consider. Despite a few omissions, all in all this paper is a great discussion of the treatment of type 2 diabetes in accordance with the principles of evidence based medicine.

Fluoroquinolone use, aortic aneurysm and aortic dissection

From a recent study:

Importance Fluoroquinolones have been associated with collagen degradation, raising safety concerns related to more serious collagen disorders with use of these antibiotics, including aortic aneurysm and dissection.

Objective To examine the relationship between fluoroquinolone therapy and the risk of developing aortic aneurysm and dissection.

Design, Setting, and Participants We conducted a nested case-control analysis of 1477 case patients and 147 700 matched control cases from Taiwan’s National Health Insurance Research Database (NHIRD) from among 1 million individuals longitudinally observed from January 2000 through December 2011. Cases patients were defined as those hospitalized for aortic aneurysm or dissection. One hundred control patients were matched for each case based on age and sex.

Exposures Current, past, or any prior-year use of fluoroquinolone. Current use was defined as a filled fluoroquinolone prescription within 60 days of the aortic aneurysm or dissection; past use refers to a filled fluoroquinolone prescription between 61 and 365 days prior to the aortic aneurysm; and any prior-year use refers to having a fluoroquinolone prescription filled for 3 or more days any time during the 1-year period before the aortic aneurysm or dissection.

Main Outcomes and Measures Risk of developing aortic aneurysm or dissection.

Results A total of 1477 individuals who experienced aortic aneurysm or dissection were matched to 147 700 controls. After propensity score adjustment, current use of fluoroquinolones was found to be associated with increased risk for aortic aneurysm or dissection (rate ratio [RR], 2.43; 95% CI, 1.83-3.22), as was past use, although this risk was attenuated (RR, 1.48; 95% CI, 1.18-1.86). Sensitivity analysis focusing on aortic aneurysm and dissection requiring surgery also demonstrated an increased risk associated with current fluoroquinolone use, but the increase was not statistically significant (propensity score–adjusted RR, 2.15; 95% CI, 0.97-4.60).

Conclusions and Relevance Use of fluoroquinolones was associated with an increased risk of aortic aneurysm and dissection. While these were rare events, physicians should be aware of this possible drug safety risk associated with fluoroquinolone therapy.

A clinical approach to dysphagia

A free full text review in the American Journal of Medicine.

Diet therapy for eosiniphilic esophagitis

---is reviewed in this paper.

Options include elemental and elimination diets.

D dimer to rule out aortic dissection

From a systematic review and meta-analysis:

Results

Abstracts from 800 articles were reviewed, yielding 30 potentially relevant studies that were reviewed in full text. Five studies met all eligibility criteria. Data from 4 studies (1,557 participants) that used a D-dimer cutoff of 0.50 μg/mL were pooled to estimate sensitivity, specificity, and positive and negative likelihood ratios. Overall, sensitivity and negative likelihood ratio were 98.0% (95% confidence interval [CI] 96.3% to 99.1%) and 0.05 (95% CI 0.03 to 0.09), respectively. These measurements had little statistical heterogeneity. Specificity (41.9%; 95% CI 39.0% to 44.9%) and positive likelihood ratio (2.11; 95% CI 1.46 to 3.05) showed significant statistical heterogeneity. When applied to a low-risk population as defined by the American Heart Association (prevalence 6%), the posttest probability for acute aortic dissection was 0.3%.

Conclusion

This meta-analysis suggests that a negative D-dimer result may be useful to help rule out acute aortic dissection in low-risk patients.

CVP: not useless if you use it right

From a review:

Critical care physicians frequently try to manipulate the preload of the heart to optimize cardiac function. There is, however, still debate as to what actually indicates the preload of the heart.

Recent findings: Although central venous pressure (CVP) is commonly used to estimate cardiac filling, it is often argued that it is a poor indicator of preload. This is likely true if one does not understand what preload is, principles of measurement with fluid filled systems, the effect of respiratory efforts on the measurement, the physiological determinants of CVP, and finally which point on the tracing to use as the estimate of the preload of the heart. When these are considered, however, the value of the CVP at the base of the ‘c’ wave gives a good indication of cardiac preload and a value which can be followed.

Summary: When properly measured CVP can be a useful guide to the filling status of the right ventricle. CVP is especially useful when followed over time and combined with a measurement of cardiac output. Importantly, preload is only one of the factors determining cardiac output and it must be integrated into a comprehensive approach that takes into account changes in cardiac function and the return of blood to the heart. Finally, the specific value of preload does not indicate volume responsiveness.

Chagas disease

This free full text review in the American Journal of Medicine focuses on the cardiac manifestations.

Neurocritical care of patients with cerebral vein thrombosis

From a review:

Recent findings: The mainstay of treatment in CVT is systemic anticoagulation even in the setting of intracerebral hemorrhage. Nonrandomized studies and case series suggest that endovascular therapy in CVT is relatively safe, and can improve outcomes in the small subset of CVT patients with neurologic deterioration despite anticoagulation.

Summary: Despite a generally favorable prognosis, one in four patients with CVT develop neurological deterioration in the acute phase. Predisposing factors include a neurological deficit or seizures at onset, deep venous thrombosis, venous infarctions, or intracranial hemorrhage with mass effect and an underlying thrombophilia. More randomized trials are needed to compare the benefits of anticoagulation and endovascular therapy.

Will the computer someday replace the physician as diagnostician?

With the growing enthusiasm over Watson and other forms of high technology decision support has come the nutty idea that computers may eventually surpass clinicians in the diagnostic process. Taking that idea to its full extent, in such a world the role of doctors would be restricted. The need for clinicians would be gone though we would still need providers to navigate the EMR and coordinate care (essentially secretarial duties), do procedures and maintain a “human touch” in healthcare through education, counselling and other types of social interaction. Could this ever come to pass?

It has already been the subject of an experiment, the conditions of which gave the idea the best possible chance to work in two ways. First, the experiment was conducted in what is arguably one of the most mechanistic and formulaic areas of diagnostic medicine. Second, it's been going on, repeated time and time again with generation after generation of software “improvement,” for decades. I am referring, of course, to computerized interpretation of electrocardiograms. Despite being given every conceivable chance it has failed. From a recent review on the topic:

The use of digital computers for ECG processing was pioneered in the early 1960s by two immigrants to the US, Hubert Pipberger, who initiated a collaborative VA project to collect an ECG-independent Frank lead data base, and Cesar Caceres at NIH who selected for his ECAN program standard 12-lead ECGs processed as single leads. Ray Bonner in the early 1970s placed his IBM 5880 program in a cart to print ECGs with interpretation, and computer-ECG programs were developed by Telemed, Marquette, HP-Philips and Mortara. The “Common Standards for quantitative Electrocardiography (CSE)” directed by Jos Willems evaluated nine ECG programs and eight cardiologists in clinically-defined categories. The total accuracy by a representative “average” cardiologist (75.5%) was 5.8% higher than that of the average program (69.7, p less than 0.001).

Those results don't say much for the cardiologists either but that's a topic for another discussion.  In a green journal editorial in 2012 Dr. Joseph Alpert cited additional research from the 1970s:

In 1976, I was involved in one of the earliest evaluations of 5 competing computer programs that interpreted electrocardiograms (ECGs).1 At that time, computer interpretation of ECGs was just beginning to make its way into hospitals in the United States and abroad. Dr Arthur Hagan and I evaluated the accuracy of the different computer interpretations compared with our own experienced analysis of more than 100 ECGs with various well defined abnormalities.

The results were illuminating. The computer interpretations were often wrong, particularly with respect to arrhythmia identification. Furthermore, the different computer ECG readings from the 5 programs often were surprisingly different. The conclusion of this early study was that computers were not as accurate in reading ECGs when compared with experienced cardiologists. We suggested that all computer-read ECGs should be over-read by an experienced physician. In the end, this study showed that the overall accuracy score for the computer ECG programs was approximately 80%, and as already noted, the computer was particularly poor on arrhythmia interpretation.

Of note, Alpert cites no improvement in over 30 years. Again from the editorial:

This is still the situation today with all ECGs with computer diagnoses over-read by an experienced physician, usually a cardiologist. Of note, when I am the over-reading cardiologist in our hospital, I still find that the computer reading of the ECG is incorrect approximately 20% of the time.

Because we often rely on the ECG to supply the critical data to guide decision making in very ill patients, this is unacceptable. And it hasn't improved in decades. These numbers were derived using artificial conventions. The results would certainly be even worse against more nuanced standards based on subtle ECG patterns.

Alpert suggests the reason for such poor results:

What is the reason that the most sophisticated computer ECG interpreting software makes so many mistakes? I think the answer lies in the remarkable and extensive capacity of the human brain to recognize visual patterns. This capacity is the reason that a person with minimal prior instruction can recognize a van Gogh painting without looking at the accompanying label. The distinctive style of van Gogh is easily recognized by the highly complex visual pattern recognition system of our central nervous system... Today, we apply this ability in a variety of areas, including athletic endeavors, police investigations, aesthetics, and many other venues, including the interpretation of ECGs.

Based on this explanation and the lack of progress over time it would appear unlikely that the computer will supplant the clinician in ECG interpretation let alone in other areas of diagnostic evaluation that are far more complex and less mechanistic.

Cardiac manifestations in ankylosing spondylitis

From a recent paper:

Methods

Transthoracic echocardiography was performed in 187 patients (105 men), mean age (SD) 50 (13) years, and mean disease duration 24 (13) years, and was related to demographic, clinical, radiographic, electrocardiographic, and laboratory data.

Results

Aortic regurgitation was found in 34 patients (18%; 95% confidence interval [CI], 12%-24%): mild in 24, moderate in 9, and severe in one. The prevalence was significantly higher than expected from population data. Conduction system abnormalities were documented in 25 patients (13%; 95% CI, 8%-18%), and significantly more likely in the presence of aortic regurgitation (P = .005), which was related to increasing age and longstanding disease, and increased from ∼20% in the 50s to 55% in the 70s. It was also independently associated with disease duration, with higher modified Stoke Ankylosing Spondylitis Spine Score, and with a history of anterior uveitis. HLA-B27 was present in similar proportions in the presence vs absence of aortic regurgitation. For comparison, clinically significant coronary artery disease was present in 9 patients (5%; 95% CI, 2%-8%).

Conclusion

Patients with ankylosing spondylitis frequently have cardiac abnormalities, but they more often consist of disease-related aortic regurgitation or conduction system abnormalities than manifestations of atherosclerotic heart disease. Because aortic regurgitation or conduction abnormalities might cause insidious symptoms not easily interpreted as of cardiac origin, we suggest that both electrocardiography and echocardiography evaluation should be part of the routine management of patients with ankylosing spondylitis.

Brugada syndrome: the essentials

A free full text review was recently published on this topic. Some of the key questions addressed:

What is it?

Brugada syndrome is a genetically heterogeneous channelopathy, first described in 1992, capable of causing arrhythmia, syncope and sudden cardiac death.

What is the presenting arrhythmia?

PMVT or VF. Less commonly MMVT.

When should you suspect it?

In a patient with characteristic ECG findings inquire about syncope or a family history of syncope, drowning or SCD. In a patient with such a personal or family history look for characteristic ECG findings. Know the typical patterns (see below).

How do you make the definitive diagnosis?

Although features from the clinical history are said to strengthen the diagnosis the new (2013) criteria are purely electrocardiographic. From the article:

1.

BrS is diagnosed in patients with ST-segment elevation with type I morphology greater than or equal to 2 mm in greater than or equal to 1 lead among the right precordial leads V1,V2 positioned in the 2nd, 3rd, or 4th intercostal space occurring either spontaneously or after provocative drug test with intravenous administration of Class I antiarrhythmic drugs.

2.

BrS is diagnosed in patients with Type 2 or Type 3 ST-segment elevation in greater than or equal to1 lead among the right precordial leads V1,V2 positioned in the 2nd, 3rd, or 4th intercostal space when a provocative drug test with intravenous administration of Class I antiarrhythmic drugs induces a Type 1 ECG morphology.

Note that you explore along three intercostal spaces with the V1-2 electrodes in attempting to elicit the pattern. Also note that drug challenge is contraindicated in patients who spontaneously exhibit the type 1 pattern. This is because it is unnecessary according to present diagnostic criteria and may provoke arrhythmia.

What electrophysiologic mechanisms are at play?

Inhomogeneous sodium channel defects cause transmyocardial voltage gradients and inhomogeneous repolarization, leading to the arrhythmia substrate. Triggering PVCs are close coupled and arise from the RVOT and thus can be ablated as an option for patients who suffer from electrical storm.

What are the genetics of Brugada syndrome?

At least 16 genes have been identified but no known mutation is present in the majority of cases. Most of the mutations are novel, found in isolated individuals or families. It has been traditionally thought to be autosomal dominant but recent evidence indicates that the genetic picture is more complex and some cases may be polygenic.

What are the management recommendations?

For symptomatic Brugada syndrome patients (syncope, cardiac arrest) : ICD implantation.

For asymptomatic patients meeting electrocardiographic criteria: avoidance of contraindicated drugs (see this list) and management of aggravating conditions such as fever and hypokalemia.

Note: quinidine can reverse the Brugada pattern and reduce arrhythmias but is not generally recommended due to a lack of high level evidence that it improves clinical outcomes, proarrhythmic effects of its own and a lack of general availability.

Asymptomatic patients who exhibit the pattern only during certain acute illnesses or exposure to sodium channel blocking drugs are considered at very low risk.

Bacterial translocation peri cardiac arrest

This paper reviews issues related to peri arrest infection. From the abstract:

During the periarrest period, intestinal ischemia may result in barrier dysfunction and bacterial translocation, which has clear mechanistic links to inflammation and cascade stimulation, especially in patients who are treated with therapeutic hypothermia. Despite optimal management, periarrest bacterial translocation may worsen the outcome of cardiac arrest victims.

But the relationship between infection and cardiac arrest is more complex than we might imagine. Emerging evidence is beginning to suggest that antibiotics may be indicated in non-shockable out of hospital cardiac arrest. From the body of the paper:

One of the main goals both during CPR and postresuscitation period is hemodynamic optimization to preserve adequate coronary and cerebral perfusion. However, intestinal ischemia, a neglected consequence of circulatory collapse, and subsequent reperfusion may be extremely detrimental by enhancing bacterial translocation [3] . This phenomenon is likely more common in patients presenting with asystole or pulseless electrical activity (PEA) rather than ventricular fibrillation or pulseless ventricular tachycardia due to the prolongation of whole-body ischemia in nonshockable cardiac arrest. Asystole has been reported as the most common presenting rhythm in OHCA victims with bacteremia followed by PEA and ventricular fibrillation [4] , whereas, in a retrospective analysis, shockable rhythms were uncommon among patients with preexisting pneumonia compared with initial arrest rhythms in patients without pneumonia [5] . Although the initial rhythm in OHCA is rarely recorded and may have evolved to asystole at the time of the recording, we have also reported PEA as the initial cardiac arrest rhythm in severe sepsis and septic shock [6] .

Research so far has shown that more than one third of OHCA victims are bacteremic upon presentation [4] ; however, it is difficult to know if sepsis is the reason for cardiac arrest or bacteremia is a downstream effect of intestinal hypoperfusion.

Multiple purported mechanisms are discussed including the use of saline as resuscitation fluid and the use of therapeutic hypothermia.