Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial.

BACKGROUND: Studies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis. METHODS: First, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock. Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I). Next, we conducted an open-label randomized controlled trial (RCT) in which the patients who had severe sepsis with thrombocytopenia (platelet counts ≤50 × 109/L) were randomly assigned to receive antimicrobial therapy alone (control group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1 ratio (study II). The primary outcomes were platelet desialylation level at study entry, overall platelet response rate within 14 days post-randomization, and all-cause mortality within 28 days post-randomization. Secondary outcomes included platelet recovery time, the occurrence of bleeding events, and the amount of platelets transfused within 14 days post-randomization. RESULTS: The platelet desialylation levels increased significantly in the 127 septic patients with thrombocytopenia compared to the 134 patients without thrombocytopenia. A platelet response was achieved in 45 of the 54 patients in the oseltamivir group (83.3%) compared with 34 of the 52 patients in the control group (65.4%; P = 0.045). The median platelet recovery time was 5 days (interquartile range 4-6) in the oseltamivir group compared with 7 days (interquartile range 5-10) in the control group (P = 0.003). The amount of platelets transfused decreased significantly in the oseltamivir group compared to the control group (P = 0.044). There was no difference in the overall 28-day mortality regardless of whether oseltamivir was used. The Sequential Organ Failure Assessment score and platelet recovery time were independent indicators of oseltamivir therapy. The main reason for all of the mortalities was multiple-organ failure. CONCLUSIONS: Thrombocytopenia was associated with increased platelet desialylation in septic patients. The addition of oseltamivir could significantly increase the platelet response rate, shorten platelet recovery time, and reduce platelet transfusion. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-16008542 .

[Transrectal high-intensity focused ultrasound with the Sonablate 500 for the treatment of prostate cancer].

OBJECTIVE: To evaluate the clinical effect of transrectal high-intensity focused ultrasound (HIFU) in the treatment of prostate cancer (PCa). METHODS: A total of 57 PCa patients, 27 localized and 30 advanced, underwent transrectal HIFU with the Sonab- late 500, the localized group treated by transrectal HIFU only, while the advanced group by transrectal HIFU combined with androgen ablation. RESULTS: For the HIFU treatment, the mean operating time, hospital stay and follow-up were 111 mm (ranging from 86 to 153 mm), 3.2 days (ranging from 2 to 18 days) and 18 months (ranging from 6 to 30 months), respectively. The biochemical disease-free rates at 1, 2 and 3 years in the localized group were 86%, 81% and 79%, respectively. While in the advanced group, the serum prostate specific antigen (PSA) was < 4.0 microg/L in 26 cases ( < 0.51 microg/L in 20) and the prostate volume decreased more than 50% in 21 cases after treated for an average of 8 months (ranging from 3 to 24 months). After transrectal HIFU prostate ablation, the prostate volume reduced, serum PSA lowered, Qmax raised and IPSS improved significantly (P < 0.05). No serious complications occurred including severe urethrorectal fistula and incontinence. CONCLUSION: Transrectal HIFU is a safe, effective and minimally invasive therapy for patients with prostate cancer.