Prophylactic use of levosimendan in pediatric patients undergoing cardiac surgery: a prospective randomized controlled trial.

BACKGROUND: The administration of levosimendan prophylactically to patients undergoing cardiac surgery remains a controversial practice, and few studies have specifically assessed the value of this approach in pediatric patients. This study therefore sought to explore the safety and efficacy of prophylactic levosimendan administration to pediatric patients as a means of preventing low cardiac output syndrome (LCOS) based upon hemodynamic, biomarker, and pharmacokinetic readouts. METHODS: This was a single-center, double-blind, randomized, placebo-controlled trial. Patients ≤ 48 months old were enrolled between July 2018 and April 2019 and were randomly assigned to groups that received either placebo or levosimendan infusions for 48 h post-surgery, along with all other standard methods of care. LCOS incidence was the primary outcome of this study. RESULTS: A total of 187 patients were enrolled, of whom 94 and 93 received levosimendan and placebo, respectively. LCOS incidence did not differ significantly between the levosimendan and placebo groups (10 [10.6%] versus 18 [19.4%] patients, respectively; 95% confidence interval [CI] 0.19-1.13; p = 0.090) nor did 90-day mortality (3 [3.2%] versus 4 [4.3%] patients, CI 0.14-3.69, p = 0.693), duration of mechanical ventilation (median, 47.5 h and 39.5 h, respectively; p = 0.532), ICU stay (median, 114.5 h and 118 h, respectively; p = 0.442), and hospital stay (median, 20 days and 20 days, respectively; p = 0.806). The incidence of hypotension and cardiac arrhythmia did not differ significantly between the groups. Levels of levosimendan fell rapidly without any plateau in plasma concentrations during infusion. A multiple logistic regression indicated that randomization to the levosimendan group was a predictor of LCOS. CONCLUSIONS: Prophylactic levosimendan administration was safe in pediatric patients and had some benefit to postoperative hemodynamic parameters, but failed to provide significant benefit with respect to LCOS or 90-day mortality relative to placebo. TRIAL REGISTRATION: Name of the registry: Safety evaluation and therapeutic effect of levosimendan on the low cardiac output syndrome in patients after cardiopulmonary bypass. TRIAL REGISTRATION NUMBER: ChiCTR1800016594. Date of registration: 11 June 2018. URL of trial registry record: http://www.chictr.org.cn/index.aspx.

[Expression of HPV16 E6 protein in nonneoplastic epithelial disorder of the vulva and squamous cell carcinoma of the vulva].

OBJECTIVE: To investigate the expression of high risk human papilloma virus (HPV) 16-E6 protein in non-neoplastic epithelial disorders of the vulva (NNEDV) and squamous cell carcinoma of the vulva (VSCC), and to explore whether HPV16-E6 protein is the etiological factor in NNEDV and its correlation with squamous cell carcinoma of the vulvae. METHODS: We detected HPV16-E6 protein expression in 15 normal vulvae cases, 40 NNEDV cases and 45 VSCC cases by immunohistochemistry SP method. RESULTS: The positive rate of HPV16-E6 in different vulva tissues: was 0% in the normal vulva, 30% in NNEDV and 66.67% in VSCC, respectively. The overall positive rate and two two comparison had statistical significance. In the NNEDV group, the positive rate of squamous hyperplasia type and lichen sclerosus type was 35% and 25%, respectively, with no statistical significance (P>0.05), but higher than that in the normal vulva skin group (P<0.05) and lower than that in the VSCC group (P<0.05). The positive rate of HPV16-E6 in VSCC was 66. 67%. The positive rate increased with the clinical stage. The positive rate between Phase I and Phase II, and that between Phase I and Phase III had statistical significance (P<0.017), but that between Phase II and Phase III had no statistical significance (P>0.017). The positive rate gradually decreased with the tumor differentiation. The difference in well-differentiated and poorly differentiated, moderately and poorly differentiated had statistical significance (P<0.017), but that of well-differentiated and moderately differentiated had no statistical significance (P>0.017). The positive rate of lymph node metastasis VSCC was significantly higher than that of non-lymph node metastasis VSCC (P<0.05). CONCLUSION: HPV infection may be an etiological factor for NNEDV. The rise of HPV16-E6 positive rate may be related to the occurrence and development of vulvar squamous cell carcinoma.