Serial Monitoring and Hyperimmunoglobulin versus Standard of Care to Prevent Congenital Cytomegalovirus Infection: A Phase III Randomized Trial.

INTRODUCTION: Nonrandomized studies support the potential of cytomegalovirus hyperimmunoglobulin (CMV-HyperIg) in preventing maternofetal CMV transmission, but prospective interventional studies show equivocal results. We pre-sent a prospective phase-III international randomized open-label trial on the potential effect of CMV-HyperIg following serial monitoring of CMV serostatus. METHODS: CMV-seronegative pregnant women (gestational age [GA] <14 weeks) were 1:1 randomized to monthly CMV-serostatus monitoring and CMV-HyperIg upon seroconversion (treatment), or routine prenatal care with CMV-serostatus testing at end of pregnancy (control). Ethical considerations required that control subjects with confirmed seroconversion be offered Cytotect®. The primary endpoint was the proportion of fetuses/newborns with congenital CMV infection. Secondary endpoints included neonatal CMV disease and safety during the 24-month follow-up. RESULTS: The treatment arm counted 4,800 randomized subjects: 52 seroconverted (median GA 24 [11-35] weeks), of which 45 completed follow-up. The control arm counted 4,735 randomized subjects: 42 seroconverted, of which 34 completed follow-up (evaluable data for 28 newborns) and 8 subjects chose off-label Cytotect®. Congenital CMV rates were 13/28 newborns (46.4% [CI 27.51; 66.13]) vs. 16/45 newborns (35.6% [CI 21.87; 51.22]) in control and treated arms, respectively (p = 0.46). Newborn CMV disease was mostly mild and spontaneously resolving. There were no major safety concerns. The target sample was not reached within an acceptable time frame. CONCLUSIONS: Serial monitoring of CMV serostatus with CMV-HyperIg treatment was associated with a mild nonsignificant reduction in the vertical CMV transmission rate. Studies on the optimal preventive strategy are hampered by epidemiological and ethical challenges and should focus on GA-dependent transmission rates and accurate dating of infection.

An open-label, randomized efficacy and safety trial of subcutaneous and intramuscular BT088 (Fovepta) human hepatitis B immunoglobulin in neonates of HBV-carrier mothers.

OBJECTIVE: The objective of the study was to assess the efficacy and safety of subcutaneously (SC) and intramuscularly (IM) administered BT088 (Fovepta) human hepatitis B immunoglobulin in neonates of hepatitis B surface antigen (HBs/HBsAg)-positive mothers in the prevention of hepatitis B infection. METHODS: This was an open, prospective, multicenter trial, in which infants were randomized to receive a single SC or IM dose of BT088 (200 IU, 0.4 mL) within 12 h of birth simultaneously with active vaccination against hepatitis B. The primary efficacy variable was the response rate, defined as the proportion of infants whose anti-HBs concentration was negative at predose and ≥100 IU/L 48 to 72 h postdose. RESULTS: The full analysis set included 31 neonates (17 SC and 14 IM). Response was experienced by 30 (96.8%) of 31 infants who received BT088 by either route of administration. The median postdose anti-HBs concentration was 261.2 IU/L. One neonate had a postdose anti-HBs level lower than 100 IU/L (81.0 IU/L). No infant experienced seroconversion during the 7- to 15-month follow-up. BT088 was well tolerated, with no allergic-like, or injection-site reactions observed. CONCLUSION: SC and IM administration of 200 IU (0.4 mL) BT088 resulted in protective serum anti-HBs titers within 72 h of administration in newborn infants and was well tolerated and effective.

Abdominal radical trachelectomy: a fertility-preserving option for women with early cervical cancer.

Abdominal radical trachelectomy is a fertility-preserving alternative to radical hysterectomy or chemoradiation for young women with stage IA2 to IB cervical cancers. Thirty-three patients were offered this procedure. The mean age was 30.5 years (range 23-37). Three procedures were abandoned because of positive pelvic nodes (two patients) and involvement of the margin between the amputated cervix and uterine fundus (one patient). Of the remaining 30 patients, 10 had stage IA2 tumours, 15 had stage IB1 and 5 had stage IB2. During follow up of a median of 47 months (mean 32 months, range 14-75 months), no recurrences have been detected. A normal menstrual pattern resumed within eight weeks of surgery in all but two patients. Five patients attempted to conceive. Three women have fallen pregnant, resulting in one first trimester miscarriage and two caesarean section deliveries at term. Our experience suggests that abdominal radical trachelectomy provides a method of treating women with stage IA2 to IB cervical cancers with conservation of fertility without apparently compromising recurrence or survival rates. It appears to provide equivalent oncological safety to a standard Wertheim hysterectomy using a technique familiar to all practising gynaecologic oncologists.

[Changes of cell mediated immunity in malignant ovarian tumor patients after operation] / A sejtes immunitás (NK-, K-sejtek) változása rosszindulatú petefészek-daganatos betegek mûtéti kezelése során.

OBJECTIVES: The authors discuss upon the changes in the two cell types involved in cell mediated immunity (Killer and Natural Killer) as a result of operation in malignant ovarian tumor atients. METHODS: They study the preoperative and postoperative cell mediated immunity of 28 malignant cystadenocarcinoma cases (FIGO stage I/a-III/c). To determine the maximum K and NK cell activity they used the kinetic model of cytotoxicity enzyme. RESULTS AND CONCLUSIONS: They conclude that operation of malignant ovarian tumors had no significant influence on K and NK cell activity. They hypothesize that unchanged cell mediated immunity seems to be independent of malignant tumors, especially in these conditions. We need further information about this change of cell mediated immunity.