Faculty Bibliography

OBJECTIVES/OBJECTIVE:To explore the outcome of monochorionic monoamniotic (MCMA) twin pregnancies affected by twin-to-twin transfusion syndrome (TTTS). METHODS:Medline and Embase databases were searched. The primary outcome was intra-uterine death (IUD); secondary outcomes were: miscarriage, single IUD, double IUD, neonatal death (NND), perinatal death (PND), presence of at least one or both survivors and preterm birth (PTB) <32 weeks of gestation. All these outcomes were assessed in MCMA twins affected by TTTS not undergoing intervention and in those treated with amniodrainage, laser therapy and cord occlusion. Sub-group analysis including cases diagnosed <24 weeks of gestation was also performed. Random-effect meta-analyses of proportions were used to analyze the data. RESULTS:Seventeen retrospective cohort studies (890 MCMA twin pregnancies, 46 affected by TTTS) were included in the review while there was no randomised trial comparing the different management options in MCMA twin pregnancies complicated by TTTS. In cases not undergoing intervention, miscarriage occurred in 10.7% of fetuses, while the incidence of IUD, NND and PND was 24.3%, 13.5% and 32.4% respectively. PTB complicated 54.0% of these pregnancies. In cases treated by laser surgery, the incidence of miscarriage, IUD, NND and PND was 19.6%, 27.4%, 7.4% and 35.9% respectively. The incidence of PTB <32 weeks of gestation was 64.9%. In cases treated with amniodrainage, the incidence of IUD, NND and PND was 30.3%, 19.1% and 35.9% respectively. PTB complicated 78.1% of cases. Analysis of cases undergoing cord occlusion was affected by the very small number of included cases. Miscarriage occurred in 19.2%, while there was no IUD or NND of the surviving twin. PTB <32 weeks occurred in 50.0% of cases. CONCLUSION/CONCLUSIONS:MCMA twin pregnancies complicated by TTTS are at high risk of perinatal mortality and PTB. Further studies are needed in order to elucidate the optimal type of prenatal treatment in these pregnancies. This article is protected by copyright. All rights reserved.

NK cells play a significant role in reducing relapse in patients with hematological malignancies following allogeneic stem cell transplantation but NK cell number and naturally occurring inhibitory signals limit their capability. IL-15 and 4-1BBL are important modulators of NK expansion and functional activation. With an aim to overcome these limitations, cord blood (CB) mononuclear cells (MNC) were ex-vivo expanded (EvE) for 7 days with genetically modified K562-mbIL15-41BBL (MODK562) or wildtype K562 (WTK562). NK cell expansion, expression of LAMP-1, granzyme B and perforin, and in vitro and in vivo cytotoxicity against B-cell non-Hodgkin lymphoma (B-NHL) were evaluated. In vivo tumor growth in B-NHL xenografted NSG mice was monitored by tumor volume, cell number and survival. CB MNC cultured with MODK562 in comparison to WTK562 demonstrated significantly increased NK expansion (35-fold, p<0.05), LAMP-1 (p<0.05), granzyme B and perforin expression (p<0.001), and in vitro cytotoxicity against B-NHL (p<0.01). Xenografted mice treated with MODK562 CB experienced significantly decreased B-NHL tumor volume (p=0.0086) and B-NHL cell number (p<0.01) at 5 weeks and significantly increased survival (p<0.001) at 10 weeks in comparison to WTK562. In summary, MODK562 significantly enhanced CB NK expansion and cytotoxicity and enhanced survival in a human BL xenograft NSG model and could be used in the future as adoptive cellular immunotherapy post UCBT. Future directions include expanded anti-CD20 CAR modified CB NK to enhance B-NHL targeting in vitro and in vivo.

Distribution of hereditary thrombophilic gene mutations differs globally. Prothrombin gene mutation G20210A is a common prothrombotic single-nucleotide polymorphism. In this systematic review, we provide a comprehensive report of the prevalence of prothrombin G20210A across the globe. Databases [Pubmed, Web of Science, Embase] were interrogated from their inception through December 2015 for articles reporting prothrombin G20210A prevalence rates and ethnicity. Prevalence rates were organized by continent and ethnoracial ancestry. A total of 113 articles were included with a total 61 876 participants tested for prothrombin G20210A. Reported prevalence rates varied from 0 to 15.9% among ethnic groups, with higher rates seen in the thromboembolism affected cohort compared with the unaffected cohort. Carrier rate distribution is supported by known historical migration patterns of global populations. This review of prothrombin G20210A prevalence may guide resourceful screening for identification of hereditary thrombophilia in female populations of interest with hypercoagulable states.

Abstract Objective: To predict the sex of newborns using first trimester fetal heart rate (FHR). Methods: This was a retrospective review of medical records and ultrasounds performed between 8 and 13 weeks of gestation. Continuous variables were compared using Student's t-tests while categorical variables were compared using Chi-square test. Results: We found no significant differences between 332 (50.7%) female and 323 (49.3%) male FHRs during the first trimester. The mean FHR for female fetuses was 167.0 +/- 9.1 bpm and for male fetuses 167.3 +/- 10.1 bpm (p = 0.62). There was no significant difference in crown rump length between female and male fetuses (4.01 +/- 1.7 versus 3.98 +/- 1.7 cm; p = 0.78) or in gestational age at birth (38.01 +/- 2.1 versus 38.08 +/- 2.1 weeks; p = 0.67). The males were significantly heavier than females (3305.3 +/- 568.3 versus 3127.5 +/- 579.8 g; p < 0.0001) but there were no differences in the proportion of small for gestational age (SGA), average for gestational age (AGA) and large for gestational age (LGA) infants. Conclusions: We found no significant difference between the female and male FHR during the first trimester in contrast to the prevailing lay view of females having a faster FHR. The only statistically significant difference was that males weighed more than female newborns.

Review of the article 'Milk intake and risk of mortality and fractures in women and men: cohort studies' by Michaelsson, Karl, et al (http://dx.doi.org/10.1136/bmj.g6015)

BACKGROUND: Coexistence of complete mole and a live fetus is uncommon (1:22,000-100,000), more so with euploidy. CASE: We present a case of a molar pregnancy with a euploid fetus who had close fetal evaluation for second trimester bleeding. The patient presented at 29 weeks' pregnancy with decreased fetal movements, a result of fetomaternal hemorrhage. She underwent cesarean section and delivered a live infant. By close follow-up and a multidisciplinary approach, the appropriate diagnosis and a favorable outcome were achieved. Both mother and the child at 5 years of age are doing well. CONCLUSION: Detailed anatomic and molecular studies demonstrated a complete mole resulting from confined placental mosaicism, with molar tissue showing a single paternal allele at 8/8 informative loci, all shared with the fetus, thus this coexistent molar pregnancy was not that of a separate conceptus.