Shortcuts-This Week in the Journals

January 22, 2008

120px-mount_rainier_7431.jpgCommentary by Sean Cavanaugh MD, Associate Editor, Clinical Correlations

If you think the modern scientific literature is reading more and more like science fiction each day, get a load of this: apparently they are growing hearts in Minneapolis. More than an interestingly macabre headline, this represents a significant advancement toward a dream long held by transplant physicians, and allows for a more vivid imagining of the day when we have the technology to grow organs from an individual’s own stem cells. The accomplishment, many years away from practical use, is being called whole organ decellularization. It  involved taking cadaveric rat hearts, washing them clean of cells with a commercially available detergent, re-seeding the remaining extracellular matrix with neonatal cardiac and aortic endothelial cells, and placing the re-seeded hearts in a bioreactor that provided coronary perfusion with an oxygenated culture medium. And presto! – in no time at all, the researchers saw synchronous paced contractions in the hearts. The functional fitness of these extra-corporeally manufactured hearts has yet to be tested or determined, and they required huge numbers of cells to manufacture, but this certainly reperesents a major step forward in realizing the dream of whole organ reproduction. Combined with the recent advances in induced pluripotential stem cells, scientists are quickly assembling the key ingredients to make this dream happen.

And as if that were not enough, Morgellons syndrome (that creepy “dermopathy of undetermined cause” that is associated with unknown fibers sprouting from the skin, confusion, and mood disorder) made the headlines again this week when the CDC announced that that are stepping up their investigation and enlisting the US Army’s help. Both the Washington Times and The Washington Post magazine ran stories. Mutant worms? Aliens? Stay tuned…

Aspirin Resistance. The term has been bandied about for a few decades now and there is still no consensus on what the term means and what, if any, the clinical correlations are. But if it is a problem, it is a widespread one: data suggests that upwards of 30% of human beings (estimates range 12- 30%) are resistant to the platelet inhibiting effects of aspirin. A meta-analysis from this week’s BMJ, corroborates the findings of a similar meta-analysis in last year’s Archive of Internal Medicine (Arch Int Med 2007: 167:1593-9) and suggests that folks who have aspirin resistance (as determined by a variety of different laboratory techniques), have an almost fourfold greater risk of major adverse vascular events. The commonly used adjunctive therapies (tirofiban and clopidogrel) did not seem to make much of a difference – nor did the dose of aspirin used. It was a heterogenous review of 20 different studies and no unifying definition or lab assay was used for restrictive criteria; as such this analysis does little to elucidate the thinking on the etiology of aspirin resistance, but it does add credence to the idea that aspirin resistance, very broadly defined, has significant clinical consequences.

So we read a meta-analysis in last month’s Annals of Internal Medicine that Vitamin D therapy did not consistently reduce the levels of PTH, nor did they seem to reduce the risk for death, bone pain, vascular calcification or parathyroidectomy in patients with chronic kidney disease.  Minus one for Vitamin D. But it’s a new year, and two new articles are shining a different light on Vitamin D. A 5 year follow-up of hip bone density in elderly women in Perth, Australia demonstrated preserved density in women given high dose calcium supplementation plus 1,000 IU of Vitamin D (ergocalciferol) – but not for women given only high dose calcium. The findings were most significant in women with a low baseline level of Vitamin D. This study did not find any differences in clinical endpoints specifically, but does lend some credibility to the meta-analyses that have found a decrease in fracture risk in women taking high dose vitamin D and calcium.

So probably good for the bones, but is Vitamin D good for the heart? HUH? A study in Circulation this week reported that individuals with Vitamin D deficiency from the Framingham Offspring Study cohort demonstrated a graded risk for the development of cardiovascular disease. Multivariable-adjusted hazard ratios were 1.53 for patients with a Vitamin D level between 10 and 15 ng/mL and 1.8 for patients with Vitamin D levels below 10 ng/mL. While it may be that a lack of Vitamin D is bad for the heart, it remains to be seen whether or not supplementing Vitamin D confers cardioprotection. But when you consider this study together with the suggestion from a very broad meta-analysis published last year in Archives of Internal Medicine that Vitamin D supplementation was associated with lower all-cause mortality, Vitamin D pills are looking good.

Finally, an article published early on-line this week in the Annals of Internal Medicine documents a community outbreak of multi-drug resistant community acquired MRSA in a population of men who have sex with men in San Fransisco. The USA300 strain of MRSA (which historically been sensitive to many agents other than B-lactams) has made headlines for the past few years and there have been a few reports of multi-drug resistant USA300, but this is the first time that an outbreak has been well-documented. And although it is still susceptible to rifampin and trimethoprim/sulfamethoxizole as well as other antibiotics, it is still cause for concern: the plasmid that determines multidrug resistance in multidrug-resistant USA300 belongs to a class of conjugative plasmids that could readily accept transposons encoding resistance to aminoglycosides, trimethoprim, vancomycin, and other antimicrobials, potentiating the emergence of even more resistant community-associated MRSA.

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