Second, early discontinuance of lenalidomide maintenance therapy based on an increased incidence of adverse events may influence the statistical power of therapeutic outcomes. Finally, population characteristics, crossover designs with the probable risk of inadequate washout period, differing lenalidomide schedules and dosages, and use of concomitant drugs may have resulted in a somewhat speculative interpretation of our analysis. Also, patients’ ages in the included studies ranged from 22 to 91 years, and efficacy in older individuals is not necessarily the same as in younger individuals. Separate subgroup analysis should be done for older vs. younger adults, but the data needed to conduct subgroup analysis could not be extracted from the studies. Further, because the seven trials we reviewed compared lenalidomide therapy with placebo, and not with thalidomide, no conclusion can be made regarding lenalidomide as first-line treatment over thalidomide. In summary, the findings from our meta-analysis indicate that lenalidomide therapy significantly improves response rates and increases progression-free survival in patients with newly diagnosed MM, and those receiving previous antimyleoma therapy, but it is associated with an increased risk of a number of adverse events. Obviously, pros and cons remain on the clinical efficacy of lenalidomide as first-line treatment for MM.E229 have been reported to form inter-subunit ion pairs and thereby affect the intrinsic open probability of the channel, such that the open probability of mutations E227K and E229K is greater than that of WT channels. Deletion of these residues might also increase intrinsic open probability and we therefore estimated the open probably for these channels, using the ‘PIP2 method’, assessing the increase of channel activity achieved by exposure of excised patches to saturating exogenous PIP2. Two heterozygous mutations, E227K and E229K, located within the deletion region, have previously been studied in detail: in heterozygous expression with WT subunits, both generate channels with a significant right shift in their ATP-response curves. Homozygous E227K and E229K channels also display a higher Po in single channels recordings, consistent with our patch clamp data showing that homDel and homS225T, del channels show higher Po and reduced ATP sensitivity. Interestingly, other mutations at these same residues have been shown to cause rapid current decay due to the loss of inter-subunit interactions. Based on these studies, E229 was proposed to form an ion pair with R314 from the adjacent subunit, such that disruption of this interaction would lead to inactivation. As revealed by the homology modeling in Figure 5B, E227 might also interact electrostatically with R192. Although no molecular mechanism so far has been proposed to explain the higher Po in E227K and E229K mutations, conceivably this may relate to repulsive interactions with R314 or R192. The patient carrying the S225T, del mutation had infancy-onset diabetes, as well as learning difficulties during primary school, and a single episode of seizures at 10 years of age.