Failure to clear intra-monocyte HIV infection linked to persistent neuropsychological testing impairment after first-line combined antiretroviral therapy.

HIV-associated neurocognitive disorders (HAND) persist despite plasma HIV RNA suppression with antiretrovirals (ARV). Sequestered reservoirs in the central nervous system and circulating monocytes are theorized to contribute to persistent brain injury. We previously demonstrated that elevated intracellular HIV DNA from circulating cells was associated with HAND in ARV-treated and ARV-naive subjects. We now report that failure to suppress intra-monocyte HIV DNA 3.5 years after initiating ARV is linked to persistent HAND and subjects with dementia are least likely to suppress intra-monocyte HIV DNA at 3.5 years. These findings suggest that antiviral strategies may need to target intra-monocyte HIV DNA.

Randomized trial of two different doses of pyridoxine in the prevention of capecitabine-associated palmar-plantar erythrodysesthesia.

AIM: The aim of the present study was to compare the efficacy of 200 mg versus 400 mg daily of pyridoxine in preventing or delaying the onset of palmar-plantar erythrodysesthesia (PPE) in capecitabine-treated patients. METHODS: Patients with histologically confirmed breast cancer or colorectal cancer receiving single agent capecitabine started at 2000 to 2500 mg/m(2) daily from day 1 to 14 every 3 weeks were randomly assigned to receive 200 mg or 400 mg daily of pyridoxine for PPE prophylaxis. The primary endpoint was the reduction of incidence of grade 2 or greater PPE. Secondary endpoints were reduction of severe PPE and prolongation of time to development of grade 2 or greater PPE. RESULTS: There were 56 patients in this study. The baseline characteristics were generally similar in both groups. The high dose arm had less PPE than the low dose arm (11 of 28 or 39% vs 20 of 28 or 71%, relative risk = 0.26 [0.08, 0.79], P = 0.031). Grade III PPE developed in 3 of 28 (10.7%) versus none in patients receiving 200 mg versus 400 mg pyridoxine, respectively (relative risk 2.12 [1.594, 2.819], P = 0.24). High dose pyridoxine had a longer time to development of grade 2 or greater PPE compared to the low dose arm, 87 days versus 62 days. The 400 mg pyridoxine group had, however, a worsened tumor response and tended to have greater tumor treatment failure and shorter time to treatment failure. CONCLUSION: With the limitation of sample size in this study, there was a trend to improve PPE incidence and time to event with a higher dose of pyridoxine. Further validation of these results in a larger population is warranted.

High frequency of mutation of epidermal growth factor receptor in lung adenocarcinoma in Thailand.

Recent reports have suggested influences of racial difference on the frequency of mutation of EGFR in lung cancer. We therefore sought to characterize the frequency and pattern of mutation of EGFR in lung adenocarcinoma in Thai patients. Overall, EGFR catalytic domain mutations were detected in 35/61 (57.4%). We found 29/60 (48.3%) of exon 19 deletions, 5/54 (9.3%) of exon 21 point mutations, and 1/54 (1.9%) of double-mutation of both exons. The presence of these mutations was significantly associated with non-smoking habit. In summary, we report a strikingly high prevalence of mutation of EGFR in Thai lung adenocarcinoma, which may explain the high response rate to the treatment with TKI among Asian populations.