Creatinine clearance is associated with toxicity from molecularly targeted agents in phase I trials.

OBJECTIVES: This study aimed to evaluate any correlations between baseline creatinine clearance and the development of grade 3/4 toxicities during treatment within oncology phase I trials of molecularly targeted agents where entry criteria mandate a serum creatinine of ≤ 1.5 × the upper limit of normal. METHODS: Documented toxicity and creatinine clearance (calculated by the Cockcroft-Gault formula) from all patients treated with molecularly targeted agents in the context of phase I trials within our centre over a 5-year period were analyzed. RESULTS: Data from 722 patients were analyzed; 116 (16%) developed at least one episode of grade 3/4 toxicity. Patients who developed a late-onset (>1 cycle) grade 3/4 toxicity had a lower creatinine clearance than those who did not (82.69 ml/min vs. 98.97 ml/min; p = < 0.001). CONCLUSION: Creatinine clearance (even when within normal limits) should be studied as a potential factor influencing late toxicities in the clinical trials of molecularly targeted anti-cancer drugs.

Evolution of the Achilles tendon: The athlete's Achilles heel?

The Achilles tendon is believed to have first developed two million years ago enabling humans to run twice as fast. However if the Achilles tendon is so important in terms of evolution, then why is this tendon so prone to injury - especially for those more active like athletes. The Achilles tendon had an integral role in evolving apes from a herbivorous diet to early humans who started hunting for food over longer distances, resulting in bipedal locomotion. Evolutionary advantages of the Achilles tendon includes it being the strongest tendon in the body, having an energy-saving mechanism for fast locomotion, allows humans to jump and run, and additionally is a spring and shock absorber during gait. Considering these benefits it is therefore not surprising that studies have shown athletes have thicker Achilles tendons than subjects who are less active. However, contradictory to these findings that show the importance of the Achilles tendon for athletes, it is well known that obtaining an Achilles tendon injury for an athlete can be career-altering. A disadvantage of the Achilles tendon is that the aetiology of its pathology is complicated. Achilles tendon ruptures are believed to be caused by overloading the tensed tendon, like during sports. However studies have also shown athlete Achilles tendon ruptures to have degenerative changes in the tendon. Other flaws of the Achilles tendon are its non-uniform vascularity and incomplete repair system which may suggest the Achilles tendon is on the edge of evolution. Research has shown that there is a genetic influence on the predisposition a person has towards Achilles tendon injuries. So if this tendon is here to stay in our anatomy, and it probably is due to the slow rate of evolution in humans, research in genetic modification could be used to decrease athletes' predisposition to Achilles tendinopathy.

Catheter associated bloodstream infection caused by R. radiobacter.

Rhizobium radiobacter is a gram negative bacillus that is infrequently recognized in clinical specimens but is emerging as an opportunistic human pathogen. Infections due to Rhizobium radiobacter are strongly related to the presence of foreign plastic material and effective treatment often requires removal of the device. We report a case of R. radiobacter bloodstream infection associated with a central venous catheter which was easily controlled by antimicrobial treatment and did not require removal of intravascular device. To the best of our knowledge, this is the first case report from India implicating R. radiobacter as a cause of human infection.