Research news and notes

1. How much aspirin? 

Aspirin is widely used for prevention of cardiovascular disease and stroke. In the May 9 issue of JAMA, Campbell et al [1] published a systematic review of literature trying to answer an old question: “How much aspirin is right?” After a review of literature in the English language through MEDLINE and EMBASE databases, they concluded that there is no evidence to support doses of more than 75 or 81 mg in the setting of cardiovascular disease prevention. However, higher doses did increase the risk of complications such as gastrointestinal bleeding. The authors conclude that 81 mg of aspirin is enough and should be the standard dose for everyone. The authors briefly address a very important question of individual variability in response to aspirin. They mention some studies of platelet aggregation, where multiple patients were found to be “nonresponsive” to low doses of aspirin. The authors discount these small-scale studies because large-scale clinical trials never found a benefit of higher doses.

This JAMA article is not really research, but rather a summary and interpretation of past research. Such articles may be influential. I have a problem with the article. The authors assume that a large-scale trial in many patients is the best way to answer the question “What should I prescribe for my patient?” This assumption is incorrect. Large population studies give answers that pertain to the population as a whole, not to an individual patient. The only conclusion from the large literature review is that studies that used doses of around 81 mg demonstrated a better balance between risk and benefit than those that used higher doses of aspirin. The authors assume that the same dose-response curve is true for all patients. Thus, if on average a higher dose is not beneficial in the population as a whole, the fact that some patients do not respond to lower doses can be somehow disregarded.

There is no reason to make such assumptions. The situation may be more complex with an individual patient. Let us suppose that the response to aspirin is individual and nonlinear. For example, as the dose increases, platelet aggregation first decreases and then increases again. In other words, the desired response to the drug first increases and then diminishes with increasing dose. In addition, the point of maximal benefit is different for each person. These simple assumptions reconcile the contradiction between the small-scale studies that found many nonresponders and the large-scale studies that show lack of benefit, on the average, from higher doses. Actually, there is good reason to believe that my assumption about aspirin dose-response variability is true. As far back as 1993, Helgason et al [2] found wide individual differences between patients in their response to aspirin.

Off-the-rack treatments, good for the overall studied population, always run the risk of suboptimal or frankly poor treatment for a particular patient. The answer for the future—tailor-made medicine with doses and medication choices selected based on the patient's own characteristics and needs.

2. Restoration of intervertebral disk 

Our current options for the surgical treatment of degenerated disk are limited and somewhat crude. Provided we can agree on the proper indications for each, we can do a diskectomy, or a diskectomy with fusion and usually instrumentation, or a diskectomy followed by replacement with an artificial disk. None of them are entirely satisfactory. Some form of restoration of the disk to a more normal condition could be better for the patient. A recent study by Revell et al [4] describes a novel experimental approach to disk substitution. The authors performed diskectomies in pigs, 2 in each animal. They used a mixture of hyaluronan-derived polymers mixed with homologous bone marrow cells obtained from the same animal 3 weeks before surgery. This mix was injected into the disks where nucleotomy had been performed. Control disks received nucleotomies only. When the spines were studied histologically 6 weeks after the initial surgery, the disks that were not repaired demonstrated expected changes—loss of normal structure with narrowing, fibrous tissue replacement, and disruption of the bony end plates. Disks injected with the nucleus replacement substance displayed a central region that formed a nucleus pulposus–like biconvex structure and contained viable chondrocytes forming a matrix like that of a normal disk. When this or similar repair strategies reach clinical trials, spine surgery will undergo a paradigm shift. That time is near.

3. Does esophagus retraction cause dysphagia after anterior cervical surgery? 

Dysphagia, usually temporary, is common after anterior cervical approaches to the spine. Intuitively, the apparent cause of this adverse effect is the retraction of the esophagus to expose the spine. Papavero et al [3], in a recent article in Spine, recorded epiesophageal pressure in 92 patients by inserting a transducer between their retractor and the esophagus. In 31 of the patients, they also inserted a pressure transducer into the esophageal lumen. In addition, 32 other patients who had lumbar surgery were evaluated as controls. All patients rated swallowing difficulty in the first 5 days after surgery using a 10-point score. About 50% of the patients had at least some swallowing difficulty. There was no correlation between the amount of retraction as measured by the pressure monitors and development of swallowing difficulty. Women had a higher incidence of dysphagia than men. The authors still believe that local surgery-related factors must account for the phenomenon because patients who had lumbar surgery did not develop dysphagia, as we all know from our clinical practice. However, if the degree of retraction is not the key factor, what is?