Ovarian stimulation for fertility treatments and risk of breast cancer: a matched cohort study.

STUDY QUESTION: Is there a difference in the breast cancer risk among women who underwent ART treatments compared to those who underwent medically assisted reproduction (MAR) infertility treatments or women of reproductive age in the general population? SUMMARY ANSWER: The risk of breast cancer among women treated by ART was similar to the risk among women treated by MAR and women who did not undergo fertility treatments. WHAT IS KNOWN ALREADY: Studies investigating breast cancer risk in women who have undergone fertility treatments have provided conflicting results. STUDY DESIGN, SIZE, DURATION: A retrospective, population-based cohort study included women who underwent ART or MAR treatments and women who did not undergo fertility treatments from 1994 to 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who underwent ART were matched one to one with women who underwent MAR treatments and one to one with woman from the general population of reproductive age, by year of birth and year of first delivery or nulliparity status. MAR women were also matched to ART women by treatment initiation calendar year. All included women were members of Maccabi Healthcare Services. Data regarding demographics, fertility treatments, BRCA mutation and possible confounders were obtained from the computerized database of electronic health records. The incidence of breast cancer after fertility treatments was compared to the matched controls. MAIN RESULTS AND THE ROLE OF CHANCE: Of 8 25 721 women of reproductive age, 32 366 women who underwent ART were matched with patients treated by MAR (n = 32 366) and 32 366 women of reproductive age. A total of 984 women (1.0%) were diagnosed with breast cancer (mean follow-up period, 9.1 ± 6.3 years; interquartile range [IQR], 3.8-13.7 years). The incidence rates of breast cancer per 10 000 person-years were 11.9 (95% CI, 10.7-13.3), 10.7 (95% CI, 9.6-11.9) and 10.7 (95% CI, 9.6-12.0) in the ART group, MAR group and general population, respectively. The crude risk for breast cancer was similar in the ART group compared with the general population (hazard ratio (HR) = 1.10, 95% CI, 0.94-1.28) and in the ART group compared with the MAR group (HR = 1.00, 95% CI, 0.86-1.16). Further adjustment for age, BMI, smoking, socioeconomic status and parity did not substantially impact the hazard rates for breast cancer (ART vs general population: HR = 1.10, 95% CI, 0.94-1.28; ART vs MAR: HR = 0.99, 95% CI, 0.85-1.16). Among women diagnosed with breast cancer, the prevalence of BRCA1/2 mutations and tumour staging did not differ between the ART, MAR and general population groups. Among women who underwent ART, no correlation was found between breast cancer and the number of ART cycles or the use of recombinant medications or urine-derived medications. LIMITATIONS, REASONS FOR CAUTION: The mean age of women at the end of follow-up was only 42 years thus the study was not powered to detect potential differences in the risk of postmenopausal breast cancer. In addition, we did not sub-classify the exposed patients by the reason for infertility. WIDER IMPLICATIONS OF THE FINDINGS: Breast cancer incidence following ART was comparable to that in the general population or following MAR. Women undergoing fertility treatments and their clinicians may be reassured about the safety of assisted reproduction technologies in terms of premenopausal breast cancer risk. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used and there are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Rare coding variant analysis in a large cohort of Ashkenazi Jewish families with inflammatory bowel disease.

Rare variants are thought to contribute to the genetics of inflammatory bowel disease (IBD), which is more common amongst the Ashkenazi Jewish (AJ) population. A family-based approach using exome sequencing of AJ individuals with IBD was employed with a view to identify novel rare genetic variants for this disease. Exome sequencing was performed on 960 Jewish individuals including 513 from 199 multiplex families with up to eight cases. Rare, damaging variants in loci prioritized by linkage analysis and those shared by multiple affected individuals within the same family were identified. Independent evidence of association of each variant with disease was assessed. A number of candidate variants were identified, including in genes involved in the immune system. The ability to achieve statistical significance in independent case/control replication data was limited by power and was only achieved for variants in the well-established Crohn's disease gene, NOD2. This work demonstrates the challenges of identifying disease-associated rare damaging variants from exome data, even amongst a favorable cohort of familial cases from a genetic isolate. Further research of the prioritized rare candidate variants is required to confirm their association with the disease.

Long-term follow-up of sacrocolpopexy mesh implants at two time intervals at least 1 year apart using 4D transperineal ultrasound.

OBJECTIVE: To determine, using four-dimensional (4D) transperineal ultrasound, whether the appearance, position or dimensions of sacrocolpopexy mesh implants or the degree of tissue support change in the long term. METHODS: Women who had undergone minimally invasive abdominal sacrocolpopexy for pelvic organ prolapse were invited for follow-up assessment at two consecutive visits at least 1 year apart. All participants completed a Pelvic Floor Distress Inventory questionnaire (PFDI-20) and underwent a pelvic examination by one examiner and had 4D ultrasound volumes obtained by a different examiner. Volumes were analyzed offline for mesh position with the woman at rest and on maximal Valsalva maneuver, and for mesh dimensions and characteristics on three-dimensional orthogonal planes and rendered views, with the operator blinded to the clinical data. Findings were compared between the two examinations. RESULTS: Thirty women attended follow-up assessment at two time points, a median of 22 (range, 12-37) months apart. The median age at the latter visit was 60 (range, 46-72) years, median body mass index was 25.9 (range, 20.8-31.9) kg/m2 , median parity was 3 (range, 1-7) and median time from surgery to first and second visit, respectively, was 11.2 (range, 6-26) months and 33.5 (range, 14-56) months. There were no significant differences between the two time points in symptom scores, reported satisfaction from surgery, pelvic examination findings or pelvic organ descent in any compartment according to ultrasound. While mesh dimensions of anterior and posterior arms did not change significantly over time, both arms descended less on Valsalva at the second follow-up compared with at the first (13.2 ± 6.7 mm vs 21.9 ± 10.0 mm and 9.1 ± 5.3 mm vs 16.1 ± 8.1 mm, respectively, both P < 0.001). There were no mesh erosions, but folding remained a consistent finding, occurring in 80% of women in each assessment. CONCLUSIONS: Characteristics of tissue support and dimensions of sacrocolpopexy mesh implants remained constant over long-term follow-up, with no mesh shrinkage or erosion. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Trial of labour in twin pregnancies: a retrospective cohort study.

OBJECTIVE: To assess the success rate of vaginal delivery among women with twin pregnancies; the Twin Birth Study has shown that vaginal delivery and caesarean section are equally safe for twin delivery but >40% of the planned vaginal delivery group delivered by caesarean section. DESIGN: A retrospective cohort study. SETTING: A tertiary medical centre. POPULATION: A total of 2194 women with twin pregnancies not complicated with very low birthweight. METHODS: Planned mode of delivery was documented in the woman's electronic record upon entering the delivery room. Information regarding maternal age at delivery, parity, gestational age, presentation, previous history of caesarean delivery, birthweight and Apgar score was collected from the obstetric electronic charts. MAIN OUTCOME MEASURED: Rate of vaginal twin delivery. RESULTS: Of the 2194 women included, 1311 twin pregnancies had planned caesarean delivery and 883 underwent a trial of labour. Of the 883 women who underwent a trial of labour, the rate of vaginal delivery was 86.9%, whereas the rates of caesarean delivery and combined vaginal-caesarean delivery were 11.1% and 2.0%, respectively. Presentation of second twin, gestational age and maternal age did affect the chances of success. Nulliparity [odds ratio (OR) 2.38, 95% confidence interval (95% CI) 1.4-4.05], Foley induction of labour (OR 2.33, 95% CI 1.38-3.91) and body mass index >30 kg/m(2) (OR 1.76, 95% CI 1.03-3) were independent risk factors for caesarean delivery. CONCLUSIONS: The rate of vaginal delivery among women with twin pregnancies who undergo labour can be high, especially in women who laboured spontaneously and have delivered before. TWEETABLE ABSTRACT: The rate of vaginal delivery of twins can be high, especially in women who have delivered before.

Clonal expansion of hepatocytes with a selective advantage occurs during all stages of chronic hepatitis B virus infection.

Hepatocyte clone size was measured in liver samples of 21 patients in various stages of chronic hepatitis B virus (HBV) infection and from 21 to 76 years of age. Hepatocyte clones containing unique virus-cell DNA junctions formed by the integration of HBV DNA were detected using inverse nested PCR. The maximum hepatocyte clone size tended to increase with age, although there was considerable patient-to-patient variation in each age group. There was an upward trend in maximum clone size with increasing fibrosis, inflammatory activity and with seroconversion from HBV e-antigen (HBeAg)-positive to HBeAg-negative, but these differences did not reach statistical significance. Maximum hepatocyte clone size did not differ between patients with and without a coexisting hepatocellular carcinoma. Thus, large hepatocyte clones containing integrated HBV DNA were detected during all stages of chronic HBV infection. Using laser microdissection, no significant difference in clone size was observed between foci of HBV surface antigen (HBsAg)-positive and HBsAg-negative hepatocytes, suggesting that expression of HBsAg is not a significant factor in clonal expansion. Laser microdissection also revealed that hepatocytes with normal-appearing histology make up a major fraction of the cells undergoing clonal expansion. Thus, preneoplasia does not appear to be a factor in the clonal expansion detected in our assays. Computer simulations suggest that the large hepatocyte clones are not produced by random hepatocyte turnover but have an as-yet-unknown selective advantage that drives increased clonal expansion in the HBV-infected liver.

Selective reduction in complicated monochorionic twins: prediction of obstetric outcome and comparison of techniques.

OBJECTIVES: To compare the outcomes of radiofrequency ablation (RFA) and bipolar cord coagulation (BPC) methods for selective feticide in complicated monochorionic (MC) twin gestations and to determine risk factors for adverse pregnancy outcome. METHODS: This was a retrospective cohort study of all patients with complicated MC twin pregnancy who underwent selective reduction in a single tertiary care center between 2000 and 2014. We compared the two methods with respect to various demographic, obstetric and perinatal outcome variables. RESULTS: Fifty-three selective terminations in complicated MC twin gestations were performed, 36 by RFA and 17 by BPC. Each technique resulted in a similar overall survival rate of the remaining twin (88.9% vs 76.5%, P = 0.25). Likewise, the mean procedure-to-delivery interval, the rate of spontaneous preterm delivery < 37, < 34, < 32 and < 28 weeks and the rate of preterm prelabor rupture of the membranes did not differ between the groups. However, among patients in the BPC group, there was a trend towards earlier gestational age at delivery (31.3 vs 35.0 weeks, P = 0.09) compared with in the RFA group. There was selective reduction by RFA due to selective intrauterine growth restriction (sIUGR) in 19 cases, 17 (89.5%) of which survived perinatally, with delivery at a median gestational age of 37 weeks. There were no significant differences in perinatal outcome, irrespective of whether the procedure was performed pre- or post-viability. All post-viability reductions, most of which were by RFA, resulted in perinatal survival. CONCLUSIONS: Perinatal outcome of complicated MC twin gestations undergoing selective feticide seems to be similar regardless of whether termination is by BPC or RFA. Nevertheless, RFA appears to be particularly useful in MC twins complicated by sIUGR and in cases requiring selective reduction beyond the age of viability.

Peginterferon and ribavirin for treatment of recurrent hepatitis C disease in HCV-HIV coinfected liver transplant recipients.

Achievement of a sustained virologic response (SVR) with antiviral therapy significantly improves graft survival in hepatitis C virus (HCV) monoinfected liver transplant (LT) patients. Risks and benefits of HCV therapy in HCV-human immunodeficiency virus (HIV) coinfected LT recipients are not well established. Among 89 HCV-HIV LT recipients in the HIVTR cohort, 39 (23% Black, 79% genotype 1, 83% fibrosis stage ≤ 1) were treated with peginterferon-a2a or a2b plus ribavirin for a median 363 days (14-1373). On intent-to-treat basis, 22% (95% CI: 10-39) and 14% (95% CI: 5-30) achieved an end-of-treatment response (EOTR) and SVR, respectively. By per-protocol analysis (completed 48 weeks of therapy ± dose reductions), 42% and 26% had EOTR and SVR, respectively. Severe adverse events occurred in 85%, with 26% hospitalized with infections and 13% developing acute rejection. Early discontinuations and dose reductions occurred in 38% and 82%, respectively, despite use of growth factors in 85%. Eighteen of 39 treated patients (46%) subsequently died/had graft loss, with 10 (26%) attributed to recurrent HCV. In conclusion, SVR rates are low and tolerability is poor in HCV-HIV coinfected transplant recipients treated with peginterferon and ribavirin. These results highlight the critical need for better tolerated and more efficacious HCV therapies for HCV-HIV coinfected transplant recipients.

Stepping from traditional to integrative medicine: perspectives of Israeli-Arab patients on complementary medicine's role in cancer care.

BACKGROUND: Limited research is available on the perspectives of patients with cancer regarding integration of complementary medicine (CM) in conventional supportive cancer care. The purpose of this study was to explore patients' perspectives concerning CM integration within conventional oncology settings. PATIENTS AND METHODS: A 27-item questionnaire was constructed and administered to a convenient sample of Arab patients receiving cancer care in three oncology centers in northern Israel. RESULTS: Of the 324 respondents (94.7% response rate), 124 of 313 (39.6%) reported the use of CM for cancer-related outcomes. A logistic regression model indicated that CM was used with active chemo- or radiotherapy treatment [EXP [B], 2.926, 95% confidence interval (CI) 1.276-6.708; P=0.011] and a higher degree of spiritual quest (EXP [B], 3.425, 95% CI 1.042-11.253; P=0.043). Herbal medicine was the leading CM modality (87.9% of CM users), which included the use of 28 plants and traditional remedies, of which 17 were used to improve QOL, with 5 of the herbs having potential interactions with chemotherapy. 83.1% of respondents stated that they would consult with a CM provider if CM were to be integrated into the oncology department. Patients' expectation of CM consultation was clearly associated with expectations of QOL improvement, coping with cancer, and alleviating chemotherapy's side-effects when compared with expectations of cancer cure (P<0.0001). The three leading concerns which patients expected to be improved by integrative CM treatment were gastrointestinal symptoms (63.2%), fatigue (51.9%), and pain (40.5%). CONCLUSIONS: Integrative CM consultations should focus on the improvement of QOL concomitant with safety concerns regarding potential drug-herb interactions. The need to integrate a nonjudgmental yet evidence-based CM consultation service may also be applicable to oncology institutions challenged with culturally diverse populations with a high prevalence of traditional medicine use.

Three-dimensional transperineal ultrasound for imaging mesh implants following sacrocolpopexy.

OBJECTIVE: To characterize, using three-dimensional (3D) transperineal ultrasound, the appearance, position and dimensions of mesh implants following minimally invasive abdominal sacrocolpopexy. METHODS: In women who underwent sacrocolpopexy, mesh was evaluated at rest and on maximal Valsalva, on all 3D orthogonal planes and rendered views. Mesh dimensions were obtained by 3D processing in the midsagittal and coronal planes (anterior, posterior and sacral arm) and were analyzed offline, the operator blinded to clinical data. RESULTS: Overall, 62 women, mean age 58.4 (range, 42-79) years were evaluated at a median of 9 (range, 1-26) months following surgery. The anterior arm of the mesh was caudal to the lowermost point of descent of the anterior compartment in 56 (90.3%) women, was equally positioned in five (8.1%) and was cranial in one. The posterior arm was caudal in 44 (71%) women, was equally positioned in 16 (25.8%) and was cranial in two (3.2%). The Y connection and the sacral arm of the mesh could not be adequately seen because of physical limitations of ultrasound (lower resolution at greater depth), large recurrent rectoceles, echogenic stools or folding of mesh remnants. Folding of the mesh was seen in 46 (74.2%) women, folding of the anterior arm in five (8.1%) and folding of the posterior arm in 23 (37.1%). Folding occurred caudally in 26 (41.9%) women, proximally in 11 (17.7%) and in both areas in nine (14.5%). There were no erosions. CONCLUSION: Mesh visualization following minimally invasive abdominal sacrocolpopexy procedures using transperineal 3D/four-dimensional (4D) ultrasound is feasible. Studies are needed to evaluate the correlation between ultrasound measures and prolapse recurrence or mesh erosion.

Early detection by diffusion-weighted sequence magnetic resonance imaging of severe brain lesions after fetoscopic laser coagulation for twin-twin transfusion syndrome.

OBJECTIVE: Monochorionic twins treated by fetoscopic laser coagulation (FLC) for twin-twin transfusion syndrome (TTTS) are at increased risk of neurodevelopmental impairment. Our aim was to evaluate the additional value of diffusion-weighted imaging (DWI) over fetal sonography and T2 magnetic resonance imaging (MRI) in the detection of acute ischemic cerebral lesions shortly following FLC. METHODS: This was a prospective cohort study of fetuses with TTTS treated by FLC. All fetuses underwent brain DWI and T2-MRI within 24-96 h after the procedure and a follow-up MRI at 30-32 weeks' gestation. All fetuses also had frequent ultrasound evaluation until delivery. RESULTS: Thirty pregnancies with TTTS were included in the study. Eight resulted in survival of only one twin after the procedure (Group A), while the other 22 pregnancies resulted in the survival of both twins (Group B), as assessed at the time of initial MRI. Two fetuses in Group A and four in Group B had evidence of transient bleeding in the germinal matrix. Three fetuses in Group B and none in Group A had diffuse ischemic changes in the white matter. One fetus died in utero 24 h after MRI. The other two fetuses in Group B demonstrated an acute infarct 24-48 h after the procedure. Subsequent scans at 28-29 and 32 weeks showed brain atrophy compatible with an old infarct. CONCLUSIONS: DWI can demonstrate cerebral damage immediately after FLC. Larger cohorts are needed to determine the role of fetal MRI in the prenatal assessment and follow-up of patients with TTTS.

Long-term clearance of hepatitis C virus following interferon α-2b or peginterferon α-2b, alone or in combination with ribavirin.

Sustained virologic response (SVR) is the standard measure for evaluating response to therapy in patients with chronic hepatitis C (CHC). The aim of this study was to prospectively assess the durability of SVR in the pivotal studies of peginterferon (PEG-IFN) α-2b or IFN α-2b. We conducted two phase 3b long-term follow-up studies of patients previously treated for CHC in eight prospective randomized studies of IFN α-2b and/or PEG-IFN α-2b. Patients who achieved SVR [undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of treatment] were eligible for inclusion in these follow-up studies. In total, 636 patients with SVR following treatment with IFN α-2b and 366 with SVR following treatment with PEG-IFN α-2b were enrolled. Definite relapse (quantifiable serum HCV RNA with no subsequent undetectable HCV RNA) was reported in six patients treated with IFN α-2b and three patients treated with PEG-IFN α-2b. Based on these relapses, the point estimate for the likelihood of maintaining response after 5 years was 99.2% [95% confidence interval (CI), 98.1-99.7%] for IFN α-2b and 99.4% (95% CI, 97.7-99.9%) for PEG-IFN α-2b. Successful treatment of hepatitis C with PEG-IFN α-2b or IFN α-2b leads to clinical cure of hepatitis C in the vast majority of cases.

Use of ultrasound in the clinical evaluation of women following colpocleisis.

OBJECTIVE: To assess the role of transperineal ultrasound in the postoperative evaluation of patients undergoing colpocleisis. METHODS: Patients who underwent colpocleisis between July 2009 and January 2011 completed the pelvic floor distress inventory questionnaire (PFDI-20) and underwent pelvic organ prolapse quantification (POP-Q) examination and four-dimensional (4D) transperineal ultrasound. Volumes were analyzed offline for assessment of pelvic organ descent, levator hiatal dimensions, levator avulsion trauma and the location of the colpocleisis scar. RESULTS: The study included 16 women, of mean ± SD age 75.7 ± 2.9 years, median body mass index 28 (range, 21-32) kg/m2 and median parity 2 (range, 0-5); one woman was nulliparous. Nine (56.2%) women were posthysterectomy. The median interval from surgery to ultrasound examination was 6.5 (range, 2-19) months. Most patients did not have symptoms of prolapse. The median pelvic organ prolapse distress inventory (POPDI-6) score was 37.5 (range, 0-75) and the median postoperative clinical POP-Q stage was 1 (range, 0-2). Ultrasound demonstrated clear visualization in all patients. Ten had avulsion defects (six were bilateral). Ultrasound estimated greater prolapse descent for all compartments when compared with the clinical examination. However, this difference was significant for anterior and posterior descent, but not for apical descent. In two women urethral diverticulum was detected on ultrasound; it was neither symptomatic nor clinically apparent. CONCLUSIONS: 4D transperineal ultrasound seems to be a potentially effective tool for the evaluation of vaginal anatomic and functional changes following colpocleisis surgery. Future investigation of the association between ultrasound findings and patients' subjective symptoms in a larger cohort is warranted.

Integrative oncology in the Middle East: from traditional herbal knowledge to contemporary cancer care.

BACKGROUND: Based on traditional, historical, ethnobotanical, laboratory, and clinical findings, we present research framework aiming to identify Middle Eastern herbs that are worthy of further research for their anticancer potential. METHODS: A comprehensive research project was developed by a multinational team comprising family physicians, medicine specialists, oncologists, an Islamic medicine history specialist, a traditional medicine ethnobotanist, and a basic research scientist. The project followed two consecutive phases: (i) historical and ethnobotanical search for cancer-related keywords and (ii) Medline search for in vitro and in vivo studies. RESULTS: This search yielded 44 herbs associated with cancer care. The Medline search yielded 34 herbs of which 9 herbs were reported in various clinical studies. CONCLUSIONS: This multidisciplinary survey was found to be a valuable way to identify herbs with potential clinical significance in cancer care. Based on this pilot study, it is suggested that the Middle East can serve as a valuable region for future multicultural-oriented cancer research.

Standardization of terminology of virological response in the treatment of chronic hepatitis C: panel recommendations.

The treatment paradigm for hepatitis C virus (HCV) infection is at a critical point in its evolution. The addition of a protease inhibitor to peginterferon plus ribavirin has become the new standard-of-care treatment for most patients. Data from clinical trials of new antivirals have been difficult to interpret and compare, partly because of heterogeneity in trial design, and partly because of inconsistencies in terminology used to define viral responses and the populations evaluated. Present definitions of viral responses for treatment with peginterferon and ribavirin are insufficient for novel treatment paradigms. Further, categorization of prior patient treatment experience in clinical trials, particularly of nonresponders to prior therapy, is inconsistent. Existing terms and definitions must be updated, standardized and/or redefined for easier interpretation of data and effective communication among clinicians. A panel of experts in HCV infection treatment met on 3 December 2009. Goals of the panel were to evaluate terms and definitions used traditionally in treatment with peginterferon and ribavirin, to refine and clarify definitions of existing terms that have varying meanings and to propose new terms and definitions appropriate for novel treatment paradigms emerging with development of new agents. A number of recommendations were accepted unanimously by the panel. Adoption of these terms would improve communication among investigators, enhance comparability among clinical trials, facilitate development of therapeutic guidelines and provide a standardized terminology for use in clinical practice.

Photovoltages in Polycrystalline Mosaic Solar Cells.

In some thin-film solar cells the light-absorbing layer is a mosaic of crystalline grains whose boundaries run from the back to the front of the cell. We used the semiconductor modeling software Sesame to do numerical calculations of the optoelectronic properties of such cells assuming that recombination of minority photocarriers occurs primarily at the grain boundaries. The work complements analytical results for diffusion-limited recombination at grain boundaries and dislocations. We chose idealized n-CdS/p-CdTe solar cells for illustration. We find that the open-circuit voltage, V OC, under illumination declines logarithmically with increasing ratio D/θ2, where D is the ambipolar diffusion constant governing minority-carrier transport and θ is the grain size (from 1 to 10 µm). While a decline in V OC as mobility increases is counterintuitive, this finding is consistent with related analytical results and confirms their utility. However, open-circuit voltages are about 0.04-0.10 V lower than the corresponding analytical estimates. We show that the deficit is mostly a consequence of a recombination shortcut. At open circuit, minority photocarrier currents at points closer to the n-CdS interface than to a grain boundary are directed through the conducting front layers and terminate near the "hot spot" at the intersection with the grain boundary. The shortcut lowers open-circuit voltages by about 0.05 V below the analytical estimates.

Day 5 vitrified blastocyst transfer versus day 6 vitrified blastocyst transfer in oocyte donation program.

The superiority of day 5 blastocysts compared to day 6 blastocysts in fresh cycle transfers was previously demonstrated and attributed mainly to endometrial asynchrony. Data from frozen blastocysts transfers showed conflicting results, possibly due to heterogeneous patient population and embryo quality. The aim of this study was to compare clinical pregnancy rate (CPR) and live birth rate (LBR) between transfers of vitrified day 5 blastocysts and day 6 blastocysts in oocyte donation, blastocyst-only cycles. In a retrospective, multi-center study, with a single oocyte donation program, a total of 1840 frozen embryo transfers (FET's) were analyzed, including 1180 day 5 blastocysts and 660 day 6 blastocysts transfers. Day 5 blastocyst transfers had better embryonic development and significantly higher CPRs (34.24% vs. 20.15%, P < 0.0001), higher LBRs (26.89% vs. 14.77%, P < 0.0001), less cycles to LBR (1.83 ± 0.08 vs. 2.39 ± 0.18, P = 0.003) and shorter time to LBRs (76.32 ± 8.7 vs. 123.24 ± 19.1 days, P = 0.01), compared to day 6 transfers, respectively. A multivariate stepwise logistic regression indicated, that day 5 transfer was an independent factor for CPRs (OR 1.91; 95% CI 1.43-2.54, P < 0.001) and LBRs (OR 2.26; 95% CI 1.19-4.28, P = 0.01), regardless of embryo quality, compared to day 6. In conclusion, day 5 blastocysts in oocyte donation program have significantly higher CPRs and LBRs, and present shorter time to delivery, compared to day 6 blastocysts, regardless of embryo quality.

Impact of virologic breakthrough and HBIG regimen on hepatitis B recurrence after liver transplantation.

The availability of hepatitis B immune globulin (HBIG) and several oral antiviral therapies has reduced but not eliminated hepatitis B virus (HBV) recurrence. We aimed to determine the rate of HBV recurrence after orthotopic liver transplantation (OLT) in relation to virologic breakthrough pre-OLT and HBIG regimens post-OLT. Data from the NIH HBV-OLT database were analyzed. A total of 183 patients transplanted between 2001 and 2007 followed for a median of 42 months (range 1-81) post-OLT were studied. At transplant, 29% were hepatitis B e antigen (HBeAg) (+), 38.5% had HBV DNA > 5 log(10) copies/mL, 74% were receiving antiviral therapy. Twenty-five patients experienced virologic breakthrough before OLT. Post-OLT, 26%, 22%, 40% and 12% of patients received intravenous (IV) high-dose, IV low-dose, intramuscular low-dose and a finite duration of HBIG, respectively as maintenance prophylaxis. All but two patients also received antiviral therapy. Cumulative rates of HBV recurrence at 1 and 5 years were 3% and 9%, respectively. Multivariate analysis showed that listing HBeAg status and HBV DNA level at OLT were the only factors associated with HBV recurrence. In conclusion, low rates of HBV recurrence can be accomplished with all the HBIG regimens used when combined with antiviral therapy including patients with breakthrough pre-OLT as long as rescue therapy is administered pre- and post-OLT.

Value of prenatal ultrasound and magnetic resonance imaging in assessment of congenital primary cytomegalovirus infection.

OBJECTIVE: To evaluate the outcome of pregnancies with proven and well-dated primary cytomegalovirus (CMV) infection with and without abnormal fetal ultrasound and magnetic resonance imaging (MRI) findings. METHODS: This was a prospective study of 38 singleton pregnancies with proven vertical transmission of CMV and prenatal ultrasound and MRI examinations. Entry requirements included precise dating of the pregnancy and known time of maternal infection. Neonatal follow-up was a strict requirement, all neonates having eye fundus examination, a brain ultrasound scan and a hearing evaluation. All children were followed up by specialists in child development. RESULTS: Primary CMV infection occurred during the first trimester in 10 patients, the second trimester in 19 and the third trimester in nine. Twenty-four of 29 patients with first- or second-trimester infections delivered; the other five underwent termination of pregnancy (TOP). Three patients had abnormal sonographic findings with normal MRI. Of these, two had damage to the auditory system. In both cases, infection occurred during the first trimester. In 16 patients with first- or second-trimester infection, both ultrasound and MRI exams were normal; there was one TOP but all other cases had favorable outcome, with normal hearing and developmental evaluations. The outcome of five pregnancies with subtle MRI findings and normal ultrasound exam was also favorable. None of the children infected during the third trimester was affected. CONCLUSION: The outcome of congenital primary CMV infection with normal prenatal ultrasound and MRI exams is favorable. The prognostic value of subtle MRI findings is limited and when such findings are isolated, termination of pregnancy is unlikely to be justified.

Dietary and herbal supplements use among patients hospitalized in internal medicine departments.

OBJECTIVES: To assess consumption of dietary and herbal supplements (DHS) among patients in internal medicine departments and determine whether such use is documented in their medical files. METHODS: 267 patients from three internal medicine departments of an academic medical center in Haifa, Israel were assessed prospectively with questionnaires about their DHS use in the month preceding hospitalization. DHS were categorized into vitamins & minerals, herbal supplements and others. Further data was then collected from patients' medical records on socio-demographic and medical characteristics, as well as documentation of DHS use. RESULTS: 123 patients (50.6 %) used DHS on a daily basis. Most of them (53.7 %) were using more than one DHS. DHS use was more prevalent in older (OR = 1.02 [1.001-1.036], p = 0.034) and educated (OR = 0.482 [0.252-0.923], p = 0.028) patients. Vitamins & minerals were used mainly to enhance vitality and address laboratory abnormalities, whereas herbal supplements were used mainly for gastrointestinal problems (p < 0.001). DHS use was reported to the physicians by 42 % of the patients, mostly at the patients' initiative [92 (82.1 %), p < 0.001)]. Vitamins and minerals were the most reported category of DHS (94 (57.3 %), p < 0.001). The use of DHS was reported to physicians for 112 DHS (41.8 %) but only 32 DHS (11.9 %) were documented in their medical files. The documentation of vitamins and minerals was significantly higher compared to herbal supplements documentation (29 (17.7 %) & 3 (2.9 %) respectively, P < 0.001). CONCLUSIONS: DHS are commonly used by patients hospitalized in the internal medicine departments. Many patients do not report such use to the physicians, and more strikingly, physicians do not document DHS use in patient medical files. This communication gap may have serious medico-legal ramifications due to DHS side effects and DHS interactions with other DHS and with conventional drugs.

The cosmological kibble mechanism in the laboratory: string formation in liquid crystals.

The production of strings (disclination lines and loops) has been observed by means of the Kibble mechanism of domain (bubble) formation in the isotropic-nematic phase transition of the uniaxial nematic liquid crystal 4-cyano-4'-n-pentylbiphenyl. The number of strings formed per bubble is about 0.6. This value is in reasonable agreement with a numerical simulation of the experiment in which the Kibble mechanism is used for the order parameter space of a uniaxial nematic liquid crystal.