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Background The aim of the study was to evaluate the trends of prevalence of several health risk behaviors (HRBs) and health conditions over a 10-years period in a representative sample of adolescents of Tuscany Region, Italy. Methods The study had a repeated cross-sectional design, data from the last four survey waves of EDIT surveillance (2008-2018) were used. EDIT surveillance investigates HRBs in a representative sample of students attending the upper secondary schools of Tuscany. Prevalence of 17 HRBs and health conditions were considered and analyzed by age, sex, and socioeconomic status (SES). Results A total of 21.943 students were surveyed from 2008 to 2018. Declining trends in the participation in smoking, cocaine use, driving under the influence of alcohol and drugs, and problem gambling were observed, while alcohol abuse and at-risk sexual behaviors remained unchanged or increased during the study period. During the most recent survey males resulted more frequently involved in most of the HRBs, while females more frequently reported physical inactivity, regular smoking and not using a condom. Female participation in smoking and alcohol abuse behaviors, fruit and vegetables consumption, and bullying worsened over the study period. Smoking, poor dietary habits, physical inactivity, high distress level, and obesity were more frequently observed in low SES students than in high SES students. Conclusions In conclusion findings showed various different tendencies in adolescent participation in HRBs over the course of the last decade; concerning trends in at-risk sexual behaviors and alcohol consumption and females’ risk-taking behavior on the rise require careful monitoring and intervention. Key messages • Distinct tendencies according to sex, socio-economic condition and specific health risk behavior were observed in adolescent participation in health risk behaviors over the course of the last decade. • Health promotion and prevention interventions tailored on specific health risk behaviors and population groups are needed.

Study question What are the causes and consequences of blastocyst collapse? Summary answer ∼50% of blastocysts collapsed, especially if they are aneuploid and/or morphologically-poor. Yet, no impact on the live-birth-rate (LBR) per vitrified-warmed euploid single-embryo-transfer (SET) was reported. What is known already Time-lapse-microscopy (TLM) is a powerful tool to describe the peculiar dynamics of preimplantation development. Lately, artificial intelligence (AI) has been also implemented to automatize and standardize such description. Here, we adopted AI to comprehensively portray blastocyst collapse, namely the phenomenon of embryo contraction with an efflux of blastocoel fluid and the detachment of the trophectoderm (TE) from the Zona Pellucida (ZP). Although, the causes of this event are still undetermined, small blastocyst contractions have been reported beneficial for the hatching process, while a full collapse has been associated with lower competence. Study design, size, duration Observational study including 1943 blastocysts from 643 couples cultured in the Embryoscope between January-2013 and December-2020. TE biopsy without day3 ZP drilling and comprehensive-chromosome-testing were performed. The Fairtility® software automatically registered: (i)time of starting-blastulation (tSB), (ii)starting and ending time of each collapse (tSC and tEC), (iii)blastocysts’ areas, (iv)shrinkage% [(area at SC – area at EC)/area at SC)], (v)embryo:ZP ratio at EC (area of the collapsed embryo/area of the ZP), and (vi)time of biopsy (t-biopsy). Participants/materials, setting, methods Blastocyst quality was defined according to Istanbul Consensus (11, excellent; 12-21, good; 22-13-31, average; 33-23-32, poor) and with the Fairtility implantation score (IS) as well, i.e., a continuous variable from 0 to 1 generated by the KID+ software based on the TLM videos of preimplantation development. The main outcome was the LBR per euploid SET adjusted for confounders through logistic regressions. All couple and embryo features were also investigated for their association with blastocyst collapse. Main results and the role of chance 47.3% of the blastocysts collapsed 1- to 9-times (interval between collapses: 4-8hr), and 73% of the couples had ≥1 collapsed blastocyst (1.8±1.1, range:1-8). No couple feature, though, was associated with blastocyst collapse. The longest collapses lasted 1.5±1.1 (0.13-5.1)hr, while the largest shrinkage% and embryo:ZP ratio at EC were 35±14% (10-78%) and 81±9% (33-90%), respectively. In ∼50-60% of collapses a 20-40% blastocyst volume reduction was registered, 40-60% or 20-40% in ∼15-30%, 60-80% in 0-4%. In case of multiple collapses, the first three involved smaller shrinkages. Blastocysts undergoing ≥1 collapse showed similar tSB as not-collapsing blastocysts, but progressively longer tEB and t-biopsy. The earlier the first event, the more the consecutive collapses. Notably, the poorer the morphology, the higher the risk (excellent, good, average, and poor not-collapsing blastocysts were 64%,50%,44% and 37%), number (e.g.,≥4 collapses were 0.4%,2%,4% and 8%) and duration (1.2±1.0,1.4±1.0,1.6±1.1 and 1.9±1.3hr) of blastocyst collapse. Collapsing blastocysts were significantly less euploid than non-collapsing (35% vs 47%; multivariate-OR:0.75,95%CI 0.6-0.92,p Limitations, reasons for caution Gestational and perinatal outcomes were not assessed. Other culture strategies and media shall be assessed for their association with blastocyst collapse. Perhaps, future studies from other groups and with a larger sample size might unveil a significant impact on the clinical outcomes. Wider implications of the findings Collapse is common and delays blastocyst full-expansion. Moreover, poor morphology and aneuploidies involve a higher risk of collapse(s); however, no impact was reported on the clinical outcomes after euploid SET. AI appears to increase the throughput of the analysis, but additional data are required to research the causes of collapse. Trial registration number Not applicable

Study question Is (intelligent data analysis) iDAScore v1.0 associated with euploidy at the blastocyst stage? Summary answer iDAScore v1.0 significantly correlated with euploidy (maternal age-adjusted OR:1.3 and AUC:0.72). Euploid blastocysts were ranked highest in ca.70% of the cohorts with both diagnoses. What is known already With machine learning and artificial intelligence (AI) implementation in IVF, several studies have been published mostly aimed at providing standardized and reproducible tools for gamete/embryo assessment and selection. Several of the proposed models might not be generally applicable due to their development on only a single center, small sample size and poor representation of the numerous clinical scenarios. Furthermore, the evidence has been rarely confirmed prospectively and/or in multicenter studies. Lately, the EmbryoScope+ has incorporated the iDAScore v1.0. This algorithm scores the chance of embryo implantation based on the video of blastocyst development and with no need for timing annotations. Study design, size, duration Interim analysis of a prospective study. Between April-December 2021, 189 preimplantation-genetic-testing (PGT) cycles (maternal age:38.4±4yr) with ≥1 blastocyst (N = 546 blastocysts, mean±SD:2.9±1.8, range:1-13) were included. We aimed at blindly analyzing the correlation between iDAScore v1.0 and (i) blastocyst quality estimated by senior embryologists, (ii) day of blastocyst full-expansion, (iii) chromosomal constitution diagnosed by NGS on a trophectoderm biopsy, (iv) the blastocyst to prioritize for transfer within cohorts with ≥2 blastocysts. Participants/materials, setting, methods Undisturbed culture was conducted in the EmbryoScope+. Assisted hatching was not performed and only fully-expanded blastocysts were biopsied. Morphology was assessed by 2 senior embryologists based on Gardner criteria. Average iDAScores were reported for the following groups: (i)excellent (AA)/good (AB,BA)/average (BB,AC,CA)/poor-quality (CC,BC,CB) blastocysts, (ii)day5/6/7 blastocysts, (iii)euploid/aneuploid/complex aneuploid blastocysts. Lastly, we reported how often the highest iDAScore corresponded to the highest ranked morphology (N = 143 cycles with ≥2 blastocysts) and/or euploid blastocysts (N = 79 cycles with both diagnoses). Main results and the role of chance In the study period, 546 blastocysts (iDAScore: 6.9±2.0, 2-9.7) were biopsied. The iDAScore was significantly different (Kruskal-Wallis Limitations, reasons for caution The main purpose of iDAScore v1.0, for which the algorithm was trained, is implantation prediction of untested blastocysts. Thus, once the sample size of this blinded prospective study will be large enough, we will also examine the association between iDAScore v1.0 and the implantation of euploid blastocysts. Wider implications of the findings The similar predictivity on euploidy reported between subjective senior embryologists’ grading and objective AI-powered iDAscores is promising in view of IVF automation and standardization. This is especially relevant since iDAScore v1.0 has not been trained yet to specifically predict euploidy, and its future versions could be fine-tuned accordingly. Trial registration number Not Applicable

Study question Which is the clinical value of day 7 blastocysts? Summary answer Ending embryo culture at 144 hours-post-insemination (hpi) would involve7.3%- and 4.4%-relative reductions in the patients obtaining euploid blastocysts and live birth(s)(LBs), respectively. What is known already Many studies showed that day 7 blastocysts are clinically valuable although less euploid and less competent than faster growing embryos. Nevertheless, a large variability exists in: (i) the definition of “day 7”; (ii) the criteria to culture embryos to day 7; (iii)the clinical setting; (iv) the local regulation; and/or (v) the culture strategies and incubators. Here,we aimed at ironing out these differences and portray day 7 blastocysts with the lowest possible risk of bias. To this end, we have also adopted an artificial intelligence (AI)-powered software to automatize developmental timings annotations and standardize embryo morphological assessment. Study design, size, duration Observational study including 1966 blastocysts obtained from 681 patients cultured in a time lapse incubator between January 2013 and December 2020 at a private Italian IVF center. Participants/materials, setting, methods Trophectoderm biopsy without hatching and comprehensive-chromosome-testing were performed. Blastocysts were clustered in six groups based on the time-of-biopsy every 12hr from 168hpi. Blastocyst quality, time-of-expanding-blastocyst (tEB) and duration of expansion were annotated through AI and confirmed manually. The main outcomes were euploidy-rate and LB-rate (LBR) per transfer. Lastly, patients obtaining (euploid) blastocysts, LBs, and supernumerary blastocysts, were reported based on a hypothetical 144hpi cut-off, and all relative reductions calculated. Main results and the role of chance 14.6% of the blastocysts reached full expansionbeyond 144hpi (5.9% between 144-156hpi, 7.9% between 156-168hpi, and 0.8% >168hpi). Slower blastocysts were of a worse quality based on the evaluation of both embryologists and AI. Both longer tEB and a longer duration of expansion concurred to day7 development, quite independently of embryo quality. The lower euploidy rate among day7 blastocysts is due to their worse morphology and more advanced oocyte age, rather than to a slower development per se. Conversely, the lower LBR was significant even after adjusting for confounders, with a first relevant decrease for blastocysts biopsied in the range 132-144hpi (N = 76/208, 36.5% versus N = 114/215, 53.0% in the control, multivariate-OR: 0.61, 95%CI 0.40-0.92, adjusted-p=0.02), and a second step for blastocysts biopsied in the range 156-168hpi (N = 3/21, 14.3%, multivariate-OR:0.24, 95%CI 0.07-0.88, adjusted-p=0.03). Nevertheless, when the cut-off was set at 144hpi, no significant difference was reported. In this patient population, ending embryo culture at 144hpi would have caused 10.6%-, 7.3%-, 4.4%-, 13.7%-, and 5.2%-relative reductions in the number ofpatients obtaining blastocysts, euploid blastocysts, LBs, supernumerary blastocysts without a LB and after a LB, respectively. Limitations, reasons for caution Gestational and perinatal outcomes were not assessed, and a cost-effectiveness analysis was not performed. We encourage the production of these data in other clinical settings and regulatory contexts. Wider implications of the findings Day7 culture shall be supported following a careful case-by-case evaluation. Patients shall be aware of their lower competence, yet day7 blastocysts are valuable for poor-prognosis couples, couples less compliant towards other attempts in case of failures, and couples wishing for second children. AI may improve the generalizability of these evidence. Trial registration number Not applicable

Study question Do the culture strategies, oocyte/embryo manipulations, and operators impact blastulation-rates per cohort of metaphase-II oocytes (BR per MII-oocytes) and/or live-birth-rates per single-embryo-transfer (LBR per SET)? Summary answer Undisturbed culture improved the BR per MII-oocytes, while culture drop volumes ≥80ml in the well-of-the-well system were associated with increased LBR per untested/euploid blastocyst SET. What is known already IVF lab performance is critical to achieve success in IVF. Yet, while a consensus exists on the main key-performance-indicators (KPIs), namely BR and LBR, and their inherent benchmark values, the strategies to fulfil them are still poorly standardized. The plasticity of human embryos along with the disparities in the patient populations might mask even largely different outcomes across clinics. Therefore, clear guidelines shall outline which procedures to standardize and carefully monitor in IVF laboratories. Here we investigated different embryo culture strategies, manipulations, and operators for their effect on BR and LBR per SET, adjusting the results for all main confounders. Study design, size, duration Retrospective analysis of 3705 cycles with ≥1 MII-oocyte and 2604 SETs (January2019-March2021). BR per MII-oocytes and LBR per SET were the main outcomes. Embryo-twinning was also assessed. The putative impact of culture strategies, manipulations, and operators’ expertise (0-5yr,6-11yr or > 12yr) was determined via regression analyses adjusted for possible confounders (autologous/donated oocytes, age, primary/secondary infertility and duration, sperm factor; for SET: also endometrial preparation, age at transfer, number of consecutive transfer, untested/euploid blastocyst, quality, and day). Participants/materials, setting, methods In donation cycles, only vitrified oocytes were used. In Preimplantation-Genetic-Testing (PGT) cycles, no assisted-hatching was performed and only euploid non-mosaic vitrified-warmed blastocysts were transferred. The culture strategies assessed were undisturbed (Embryoscope, Geri and Embryoscope-plus)/disturbed (KSystems), volume and approach (drops ≤30ml with single-culture or ≥ 80ml with well-of-the-well approaches), humidified/non-humidified atmosphere and media refreshed/not-refreshed. The manipulations assessed were oocyte/blastocyst vitrification (performed/not-performed), oocyte retrieval and denudation performed with oil overlay (yes/not), laser-assisted artificial-shrinkage (performed/not-performed), trophectoderm biopsy (performed/not-performed). Main results and the role of chance The only confounders on BR per MII-oocytes (overall:39.1±26.6%) were sperm factor and oocyte age. The linear regressions showed benefits for humidified atmosphere (unstandardized B-coefficient:+2.9%, p = 0.01), manipulations with oil overlay (+3.9%, p = 0.03) and drops≥80ml with a well-of-the-well approach (+4.3%, p The main confounders on LBR per SET (overall: N = 1044/2604, 40.1%) were oocyte age, number of consecutive transfer, blastocyst chromosomal status (untested/euploid), quality and day. The univariate logistic regressions showed a benefit for undisturbed incubators (OR:1.3, 95%CI 1.1-1.5, p Lastly, no feature under investigation was associated with embryo-twinning (overall: N = 23/1243, 1.9% and N = 14/1044, 1.3% per pregnancy and delivery, respectively). Limitations, reasons for caution Retrospective single center study. Only ICSI cycles and continuous culture media were assessed. Cleavage stage SETs were excluded. All operators had at least 3yr of experience. Perinatal and gestational outcomes were not evaluated. Wider implications of the findings Real-life data adjusted for confounders may unveil fluctuations in critical KPIs mainly imputable to culture strategies. An impact seldom derives from oocyte/embryo manipulations if experienced operators adopt validated protocols. An accurate interpretation of these evidence shall lead to properly designed studies with problem-solving/progress-building purposes, and guidelines to standardize culture practices. Trial registration number Not applicable

Study question Is double stimulation in the same ovarian cycle (DuoStim) a valuable strategy to improve the chance of success in couples carrier of monogenic conditions? Summary answer DuoStim is advantageous in patients indicated for preimplantation genetic testing for monogenic diseases and aneuploidy testing (PGT-M/-A) and obtaining ≤5 blastocysts after the I-stimulation. What is known already PGT-M is a well-established strategy to identify unaffected blastocysts in a cohort of embryos produced from couples carrier of single gene disorders. When PGT-M is conducted in poor prognosis and/or advanced maternal age (POR/AMA) patients, also aneuploidy-testing among unaffected blastocysts is suggested on a single biopsy. The Poseidon group stated that retrieving an adequate number of oocytes to produce ≥1 euploid blastocyst should be considered the main goal of controlled-ovarian-stimulation (COS). This task is even more complex when PGT-M is required in POR/AMA patients. Therefore, lately we started suggesting DuoStim to these couples to maximize their chance of success. Study design, size, duration Multicenter case series (2016-2021). Comprehensive description of IVF outcomes derived from DuoStim application in POR/AMA patients undergoing PGT-M. Aneuploidy-testing was also conducted on unaffected blastocysts. All results were compared between the two stimulations in the same ovarian cycle, and we reported the contribution of II-stimulations to higher chances of success. Participants/materials, setting, methods GnRH-antagonist COS was performed with recombinant-gonadotrophins and agonist-trigger. Based on the expected risk each embryo would be affected-aneuploid, DuoStim was suggested to all patients obtaining ≤5 blastocysts (day5-7 from I-retrieval). 61 patients accepted and underwent II-stimulations with the same protocol. Only ICSI, trophectoderm-biopsy, qPCR, and vitrified-warmed unaffected-euploid single-blastocyst-transfer(s) were conducted. Main results and the role of chance 90 patients (36.7±3.7yr) indicated to PGT-M/-A and obtaining ≤5 blastocysts after I-stimulations were suggested starting a II-stimulation in the same ovarian cycle. Among them, 61 accepted (67%). 7.2±4.4 and 7.4±4.2 cumulus-oocyte-complexes were retrieved after I- and II-stimulations, respectively (p = 0.7). 5.1±3.0 and 5.8±3.4 were metaphase-II oocytes (p = 0.2), resulting in 75±21% and 77±25% maturation-rates (p = 0.6). 3.6±2.1 and 4.6±2.9 2PN-zygotes were obtained (p = 0.04), resulting in 75±27% and 81±20% fertilization-rates (p = 0.19). 1.6±1.3 and 2.2±1.8 blastocysts were obtained (p = 0.04), resulting in 43±32% and 46±32% blastulation-rates (p = 0.6). Lastly, 0.5±0.7 and 0.7±1.0 blastocysts were diagnosed unaffected-euploid (p = 0.3), resulting in 35±40% and 30±36% transferable blastocyst rates per biopsied embryo, respectively (p = 0.53), and identical 10±16% transferable blastocyst rates per metaphase-II oocyte in both groups (p = 0.9). 23 (38%) and 24 (39%) patients obtained ≥1 transferable blastocyst after the I- and II-simulation, respectively. Overall, 36 (59%) patients obtained ≥1 transferable blastocyst thanks to DuoStim. To date, 57 (93%) cycles were concluded, and the cumulative live birth rate (CLBR) was 37% (N = 21/57). The patients with a LB have 1.7 surplus transferable blastocysts, and 3 patients already delivered 2 singleton healthy-LBs. The CLBR among patients undergoing the conventional strategy was 21%, no surplus transferable blastocyst is available, and no patient delivered >1 LB. Limitations, reasons for caution Observational case series based on real-life data. Of note, the adoption of DuoStim (or any other oocyte/embryo accumulation strategy) in PGT-M/-A is valuable also to amortize the costs of PGT-M set-up and genetic testing through a larger number of blastocysts. In this context, cost-effectiveness analyses in different settings are desirable. Wider implications of the findings DuoStim is a fully-personalized strategy advisable any time lower chance of success and higher treatment costs could be balanced by a larger number of blastocysts produced in a short time-frame. Adopting GnRH-antagonist protocols in these patients allows to suggest DuoStim even in progress, based on the embryological outcomes after I-stimulations. Trial registration number Not applicable

Study question How common abnormal cleavage patterns (ACP) are in IVF and what are their consequences on embryo developmental competence? Summary answer ACP might affect up to 25% of the 2PN-zygotes, independently from patients’/cycles’ characteristics, and mostly cause embryo developmental arrest around the 4-to–8-cell transition. What is known already Since its implementation in IVF, time-lapse-microscopy (TLM) allowed the standardization of embryo culture within undisturbed incubators, but it has not improved embryo selection especially if blastocyst transfer is performed. Nevertheless, TLM holds the potential for boosting our knowledge of embryo preimplantation development. In particular, a continuous observation of embryo morpho-dynamics unveiled peculiar blastomere cleavage patterns previously unidentifiable with a static morphological assessment. These events are possibly associated with massive mitotic errors, affecting both chromosomes and cytoskeletal components, as well as downstream metabolic imbalances. Still, the causes of ACP and their consequences on embryo developmental/reproductive competence require further investigation. Study design, size, duration Observational study including 75 patients (age:38.6±3.7yr, FSH:8.8±3.6IU/l, AMH:1.7±1.3ng/ml; BMI:21.4±2.4) who conducted multiple IVF cycles (N = 160; 8.7±5.0 cumulus-oocyte-complexes and 6.3±3.6 metaphase-II collected; 201±245 days between first and second cycles) in a time-lapse incubator between 2014–2020. All annotations were performed blindly by two operators and confirmed by a third in case of discordance. The outcomes were the blastulation rate after any ACP, their association between each other and with patients’/cycles’ characteristics. Participants/materials, setting, methods We included only ICSI-cycles after ovarian-stimulation with blastocyst culture conducted in the Embryoscope. Overall, 981 metaphase-II were inseminated and 677 2PN-zygotes annotated. The ACP investigated were: (i)cytokinesis-failure, formation of cytoplasmic septa without cell division; (ii)Chaotic-cleavage, disordered and uneven cleavages; (iii)Direct-unequal-cleavage (DUC), cleavage of zygotes or single blastomeres directly into 3; (iv)Rapid-cleavage, t3-t2 Main results and the role of chance Among the 2PN-zygotes, the prevalence of cytokinesis-failure was 5.9% (N = 40/677), 15.7% for chaotic-cleavage (N = 106/677), 18.6% for DUC (N = 126/677), 4.1% for rapid-cleavage (N = 28/677), 3.5% for reverse-cleavage (N = 24/677) and 24.1% for fragmentation (N = 163/677). Among the morulae, the prevalence of blastomere exclusion/extrusion was 27% (N = 109/410;1.5±1.2 excluded/extruded cells,range:1–7). The risk for reverse-cleavage was higher among 2PN-zygotes facing failed-cytokinesis (N = 8/40,20% versus N = 16/637,2.5%, OR:9.7,95%CI:3.9–24.3,p No predictive factor of ACP was identified among patients’ and cycles’ characteristics, except for higher risks of fragmentation (OR:2.6,95%CI:1.1–6.3,p= 0.04) and blastomeres’ exclusion/extrusion (OR:2.7,95%CI:1.1–7.2,p=0.04) among patients with previous experience with these events. The viable-blastocyst rate per 2PN-zygote was 45.1% (N = 305/677). It was lower in case of failed-cytokinesis (N = 12/40,30% versus N = 293/637,46%, OR:0.5,95%CI:0.25–0.99,p=0.05), chaotic cleavage (N = 20/106,18.9% versus N = 285/571,49.9%, OR:0.23,95%CI:0.14–0.39,p Limitations, reasons for caution The patients included were poor-prognosis women undergoing ≥2 cycles. We are expanding the sample size to account for all cycles conducted in time-lapse incubators. Larger sample size will provide also statistical-power to investigate the effect of ACP on blastocysts’ chromosomal and implantation competence, and more visualizations of rapid-/reverse-cleavage events. Wider implications of the findings: After ACP,developmental-arrest mostly occurs around the 4-to–8-cell transition (50–70% versus ∼30%), when embryonic-genome-activation takes place. Surviving embryos often fragment and/or exclude/extrude blastomeres at morulation, without further impact on blastulation-rates. Moreover, ACP seem independent from patients’/cycles’ characteristics. These evidence incite future Research on the biological/genetic mechanisms triggering ACP and their consequences. Trial registration number None

Study question Is cryo-storage duration associated with the outcomes after vitrified-warmed euploid single blastocyst transfer? Summary answer Lower live-birth-rates from blastocysts cryo-stored for periods longer than 3-months are mostly imputable to the worse quality of the embryos being warmed across sequential transfers. What is known already Blastocyst vitrification is crucial in modern IVF. Given its widespread application, a constant comprehensive monitoring of its effect on reproductive outcomes is pivotal. For instance, the effect of cryo-storage duration on embryo implantation potential, gestational and perinatal outcomes is object of a still ongoing investigation. The evidence in this regard are contrasting especially with regard to similar or decreased live birth rates among blastocysts subject to long-term cryo-storage. When investigating the neonatal outcomes, instead, no impact of blastocyst cryo-storage duration has ever been reported to date. Yet, data on euploid blastocysts and adjusted for quality and full-blastulation day are needed. Study design, size, duration Retrospective observational study. We included 2688 vitrified-warmed euploid single blastocyst transfers. The primary outcome was the live-birth-rates (LBR) according to cryo-storage duration clustered as ≤ 60, 61-90, 91-180, 181-360, 361-720, 721-1080 and >1080-days. The secondary outcomes were the miscarriage rate, the rates of gestational and perinatal issues among the deliveries, and the mean gestational age and birthweight among the babies born. All data were adjusted for confounders through linear or logistic regression analyses. Participants/materials, setting, methods We included all vitrified-warmed transfers (range:1-8) conducted between May-2013 and March-2020 by 1884 patients (age:38±3yr) undergoing one blastocyst stage PGT-A cycle and obtaining ≥1 euploid embryo at our private clinic. Among putative confounders, only the number of sequential transfer from the same patient, blastocyst quality (Gardner’s scheme) and full-blastulation day (5-7) significantly associated with the LBR through univariate regressions. No association was reported for sperm factor, maternal age, incubator, and culture media. Main results and the role of chance The LBR of euploid blastocysts cryo-stored for ≤60-days was 49.4% (N = 319/646) versus 48.7% (N = 292/599; OR:0.98,95%CI:0.78-1.21,p = 0.82) between 61-90-days, 42.9% (N = 291/679; OR:0.77,95%CI:0.62-0.96,p = 0.02) between 91-180-days, 41.7% (N = 169/405; OR:0.73,95%CI:0.57-0.94,p = 0.02) between 181-360-days, 34.7% (N = 50/144; OR:0.55,95%CI:0.37-0.79,p < 0.01) between 361-720-days, 53.4% (N = 63/118; OR:1.17,95%CI:0.79-1.74,p = 0.42) between 721-1080-days, and 50.5% (N = 49/97; OR:1.05,95%CI:0.68-1.60,p = 0.83) for >1080-days. However, when these data were adjusted for blastocyst quality and full-blastulation day, all the multivariate-OR were not-significant. Indeed, the longer the cryo-storage period the worse the quality of the euploid blastocysts transferred (e.g. AA-blastocysts were 74% among embryos cryo-stored for ≤90-days, but always < 70% for embryos cryo-stored for longer periods, p Limitations, reasons for caution The prevalence of first transfers decreases from ≥95% for procedures conducted ≤90-days from vitrification to 71%, 39%, 22% and 4% for procedures conducted between 91-180, 181-360, 361-720 and >720-days, respectively. However, also the sequential number of transfer was not associated with the LBR when adjusted for blastocyst-quality and full-blastulation day. Wider implications of the findings Cryo-storage by vitrification is confirmed safe in the hands of experienced operators, and its duration does not impact any outcome. This information is valuable for freeze-all cycles, but also for women cryo-preserving surplus embryos for second pregnancies; in this regard, 6.8% of the patients in this study delivered ≥2 LBs. Trial registration number not applicable

Study question Does maternal body-mass-index (BMI) associate with blastocysts’ chromosomal constitution and clinical outcomes in infertile patients undergoing preimplantation genetic testing for aneuploidies (PGT-A)? Summary answer A higher euploidy rate per biopsied blastocyst was reported among underweight women. Overweight women were instead subject to higher miscarriage (MR) and lower live-birth-rates (LBR). What is known already Different studies in the literature revealed an association between BMI and infertility, suggesting a J-shaped relationship: both underweight and overweight women can suffer from infertility issues. Even if IVF might increase the success rate in both these categories of patients, it seems insufficient per se to overcome the complex and multifactorial fertility impairment derived from unbalanced nutritional intakes. Miscarriage, in particular, is common in both underweight and overweight women. However, most of the literature is based on chromosomally-untested embryos. Study design, size, duration: Retrospective observational study. Only the first IVF cycle with ≥1 biopsied blastocyst from each woman was included. The primary outcome was the association between maternal BMI (underweight, BMI25, N = 259) and the mean euploidy rate per cohort of biopsied blastocysts (m-ER). The secondary outcomes were the association between maternal BMI with clinical (mainly MR and LBR), gestational and perinatal outcomes after first vitrified-warmed single euploid blastocyst transfers. Participants/materials, setting, methods We included 1811 women undergoing PGT-A at a private IVF center between April–2013 and March–2020. The secondary outcomes were investigated on 1125 first vitrified-warmed single euploid blastocyst transfers from all patients obtaining ≥1 transferable blastocyst. Only ICSI with ejaculated sperm and continuous culture in standard incubators were performed. Logistic regressions were conducted to identify putative confounders and adjust the results accordingly. Main results and the role of chance Except for a lower maternal age among underweight women (38.3±3.1 versus 38.9±3.4 yr, p Morphological quality and day of full-blastulation among transferred euploid blastocysts was similar in the three groups. Overweight women showed higher MR per pregnancy (N = 20/75, 26.7%, 95%CI:17.4%–38.3% versus N = 67/461, 14.5%, 95%CI:11.5%–18.2%; OR 2.0, 95%CI:1.1–3.6, p = 0.01) and lower LBR per transfer (N = 55/154, 35.7%, 95%CI:28.3%–43.8% versus N = 388/859, 45.2%, 95%CI:41.8%–48.6%; OR adjusted for euploid blastocysts’ features 0.67, 95%CI:0.46–0.96, p = 0.03). Clinical outcomes were instead similar among underweight and normal-weight women. All gestational and perinatal outcomes were comparable in the tree groups. Limitations, reasons for caution Our study is limited by its retrospective nature, and the fact that maternal BMI was measured only before oocyte retrieval and not before embryo transfer. Moreover, the reduced sample size did not allow for further relevant sub-analyses among solely obese women. Wider implications of the findings: When possible nutritional/lifestyle modifications should be encouraged to adjust maternal BMI before IVF. Overweight patients should be especially informed of their higher risk for miscarriage. Yet, BMI is just a gross marker, future studies based on body fat localization and percentage (e.g. by bioelectrical impedance analyses) are desirable. Trial registration number None

In 2015-2016, an outbreak of invasive meningococcal disease due to Neisseria meningitidis C/cc11 occurred in Tuscany, Italy, and caused 62 cases. Regional Health Authority launched an immunization campaign using quadrivalent meningococcal conjugate vaccine (MEN) in April 2015. We assessed the impact of meningococcal outbreak on population vaccination coverage, considering a pre-outbreak (2014), outbreak (2015-2016) and a post-outbreak period (2017-2018) for MEN and other vaccinations (HPV and MMR). We included all individuals (>1 year) resident in Tuscany, who received at least one vaccination dose (MEN, HPV, MMR) in the study period. We sourced anonymous data from the regional centralised register on vaccine administered, date, place and dose (for multiple-dose vaccines); birth cohort; city of residence. We analysed vaccine administration by age, time, vaccine type. We modelled MEN vaccination rate as a function of number of cases in the previous month by a quasi-Poisson model (2015-2018), and HPV and MMR vaccination using an interrupted time series analysis (2014-2018). MEN vaccinations increased significantly in 2015-2016 (average doses/month were 3400 in 2014; 25492 in 2015; 47290 in 2016). MEN immunization coverage increased during the outbreak period, peaking for age class 20-45: from 3,7% in 2014 to 10,7% in 2015 and 20,7% in 2016. MEN vaccination uptake showed a 50% increase (95% CI = 37 to 65%, P The campaign successfully increased MEN coverage mostly among young adults, although vaccination demand was associated with occurrence of cases. The campaign did not affect routine vaccination programmes, and likely contributed positively to HPV uptake. Key messages The immunization campaign triggered by meningococcal outbreak in Tuscany in 2015-2016 successfully increased coverage, mostly among young adults, without affecting routine vaccination programmes. During response campaign triggered by meningitis outbreak in Tuscany in 2015-2016, meningococcal vaccine uptake was influenced by the occurrence of cases.

Methane emissions from landfills are an important source of greenhouse gases in the UK and worldwide. This paper considers how measurements of methane emissions could be used to regulate landfills in England in order to reduce the contribution of landfilling to climate change. The paper presents the results of a number of UK studies undertaken to quantify methane emissions from landfills. The methods used have included the DIAL (Differential Absorption Lidar) technique and a tracer gas dispersion method. A method based on aerial measurements has been developed. Methane emission rates were measured at 15 biodegradable waste landfills. All of the landfills where measurements took place had an active landfill gas extraction system. A methane collection index (MCI) is calculated for each landfill using the ratio of the methane collection rate to the sum of the collection and emission rates. The values of the index in the campaigns reported here ranged from 0.28 to 0.90. The modern operational landfills surveyed achieved MCI values with a much narrower range of between 0.64 and 0.90 with an average of 0.76. This has demonstrated that it is possible for these landfills to collect a high proportion of the landfill gas. A proposed approach is presented for regulating landfills using the measured MCI. This would involve an annual measurement campaign to quantify the methane emissions and the use of the data provided by these surveys to develop an achievable but challenging MCI limit. A limit value of 0.75 for the MCI is used to illustrate the approach. An MCI that falls below the limit would trigger actions to reduce the methane emissions from the landfill.

Blood pressure ( BP) control remains unsatisfactory worldwide. Better knowledge of BP management in clinical practice is needed to develop more effective improving strategies. Using a large Italian primary care database, we selected the subjects diagnosed with hypertension, and extracted the diagnosis of myocardial infarction, angina pectoris/coronary disease, stroke/transitory ischemic attack (TIA), heart failure, atrial fibrillation, peripheral arterial disease, diabetes mellitus, the serum total cholesterol, HDL cholesterol, triglycerides, creatinine, BP, electrocardiogram, weight, height and the prescription of cardiovascular ( CV) drugs. Hypertension was recorded in 119.065 individuals (prevalence 19.3%), 19.134 (16%) had no ambulatory visit and 33.183 (27.8%) had no BP value recorded. Overall, 14.594 (21.9%) had at least one recorded diagnosis showing high CV risk. BP was controlled (mean of BP values

To evaluate prevalence of use and prescribing patterns of antiepileptic drugs (AEDs) in Italian general practice. Primary care data were obtained from the Health Search Database, a longitudinal observational database implemented by the Italian College of General Practitioners (GPs). We selected 465 061 subjects registered by the end of 2005 in the lists of 320 GPs, homogeneously distributed throughout Italy. Prevalence of AED use was assessed in the entire sample and by drug type, age group, year and main geographic area (north, centre and south/islands). Overall, 24 383 subjects (5.2%) received at least one AED prescription in the study period. Prevalence of AED use (with 95% confidence interval) increased progressively from 7.1 (6.9–7.3) in 2000 to 11.8 (11.5–12.1) in 2005 for old AEDs and from 1.1 (1.0–1.2) to 12.2 (11.9–12.5) for new AEDs. Carbamazepine, phenobarbital and valproic acid were the most common AEDs until 2003, when gabapentin became first. There were no differences in prescribing patterns in the three main geographic areas. Newer AEDs were mostly used in patients aged 65 years and older. The more widespread use of newer AEDs was for mood disorders or pain. Older AED currently remain first line drugs for epileptic disorders. An increasing use of AEDs has been recently observed over a 6-year period in Italian general practice, mostly explained by newer compounds used for conditions other than epilepsy.

Dynamic Left Ventricular Outflow Tract Obstruction: Comparison between Dobutamine and Exercise Stress-Echo A 62 years old man with high cardiovascular risk profile underwent dobutamine stress echocardiography for suspected silent myocardial ischemia; the test showed severe dynamic intraventricular obstruction (maximum gradient 210 mmHg) and was prematurely stopper for high intraventricular gradient. A maximal exercise stress-echo, performed according to Bruce protocol, showed the same response, in absence of any new asynergic area.

We report on the performances of CsI(Tl) crystals as γ-ray detectors, compared with standard NaI(Tl). Energy resolution from E γ =122 keV up to E γ =7.6 MeV and light output yield of different CsI(Tl) crystals and read-out configurations (photomultiplier tubes, photodiodes and avalanche photodiodes) have been measured.

We report on the performances of CsI(Tl)-photodiode detectors for γ-ray spectroscopy applications. Light output yield and energy resolution have been measured for different crystals and read-out configurations.

In this paper, a modified version of the packet reservation multiple-access (PRMA) protocol is proposed to provide spatially dispersed voice and data user terminals wireless access to a base station over a common short-range radio channel. An analytical approach is presented in order to derive system performance in terms of mean data message delay and voice packet dropping probability. A suitable permission probability design is also proposed to enhance system performance. Performance comparisons with an extension of the PRMA protocol to voice data systems previously reported in literature are shown to highlight the better behavior of this approach.

Motion estimation is relevant for applications of both motion-compensated image sequence processing and dynamic scene analysis of computer vision. Different approaches and solutions have been proposed for these two applicative fields. In some cases, parallel architectures and dedicated chips for motion estimation in real-time have been developed. In this paper, a low-cost REal-TIme Motion Analysis Chip, RETIMAC, is presented, which is suitable for dynamic scene analysis in computer vision applications. This chip is capable of estimating optical flow fields in real-time, and has been especially developed for project OFCOMP (Optical Flow for COunting Moving People) DTM 45 ESPRIT III MEPI. It can be profitably used also for autonomous navigation, tracking, surveillance, counting moving objects, measuring velocity, etc., and for several computer vision applications which require as a first processing step the estimation of the apparent velocity of each pixel in the image plane (e.g., optical flow, velocity field). RETIMAC implements a gradient-based solution which has been demonstrated to be more reliable and precise with respect to several solutions proposed in the literature.

Objective Since different techniques have been described for cholangiogram access after liver transplantation, we compared two different methods for patients with duct-to-duct biliary anastomoses. Methods Adult liver transplant patients from program inception in 1993 to May 2003 in whom a duct-to-duct biliary anastomosis with a T-tube choledochostomy were compared with those having a transcystic duct catheter using a rubber band. We excluded 10 patients in which a different technique was used or graft or patient survived less than 21 days. Group A ( n = 28,) had a number 10 T-tube exteriorized through the recipient main bile duct; and group B ( n = 33) a number 5 Bard ureteral stent tied to the cystic stump with reabsorbable suture and secured with a hemorrhoidal rubber ligature. Results The biliary complication rate was lower among the transcystic catheter group (9.1%, 3/33) compared to the T-tube group (35.7%, 10/28). Postcatheter withdrawal peritonitis was present in two patients in the T-tube group, one of whom required emergency laparotomy. A satisfactory postoperative cholangiogram was obtained in both groups. The transcystic catheter was withdrawn on average at 29 days, compared to 136 days in the T-tube group. Conclusions Both techniques are equally effective in obtaining a satisfactory postoperative cholangiogram. However, the transcystic catheter technique allows a significantly earlier withdrawal with fewer complications compared to the T-tube technique.

Medical scores for predicting survival are essential to stratify patients with end-stage liver disease (ESLD) for prioritization for liver transplantation (OLT). Recently the UNOS has adopted the Mayo Model for End-stage Liver Disease (MELD) score as the basis for liver allocation in the United States. We retrospectively evaluated and assessed the prognostic impact, the length of stay (LOS), and hospital charges for OLT using two severity scores (Child-Turcotte-Pugh [CTP] versus MELD) to stratify cirrhotic patients before OLT. Twenty-six consecutive adult cirrhotic patients (11 women, mean age 46 years) underwent LT between 2000 and 2002. The main causes for transplantation were alcohol and primary biliary cirrhosis. The mean CTP and MELD scores at the moment of listing for OLT were 8.9 and 16.3 points, respectively. The best discriminative values with prognostic impact in terms of outcome and costs of OLT were a Child Pugh score >/=11 points or a MELD score >/=20 points. Patients in these strata showed a significant increase in LOS in the hospital (from a mean of 12 to 22 days) and intensive care stay (from a mean of 4 to 14 days) post-OLT when compared with patients with a lower CTP or MELD score (P

We report on the performances of CsI(Tl)-photodiode detectors for γ-ray spectroscopy applications. Light output yield and energy resolution have been measured for different crystals and read-out configurations.

Epirubicin is one of the most active agents for breast cancer. The formation of epirubicin glucuronide by liver UDP-glucuronosyltransferase (UGT) is its main inactivating pathway. This study aimed to investigate epirubicin glucuronidation in human liver microsomes, to identify the specific UGT isoform for this reaction, and to correlate epirubicin glucuronidation with other UGT substrates. Microsomes from human livers were used. UGTs specifically expressed in cellular systems, as well as two UGT2B7 variants, were screened for epirubicin glucuronidation. Epirubicin, morphine, and SN-38 glucuronides were measured by high-pressure liquid chromatography. The mean +/- S.D. formation rate of epirubicin glucuronide in human liver microsomes (n = 47) was 138 +/- 37 pmol/min/mg (coefficient of variation, 24%). This phenotype was normally distributed. We screened commercially available UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, UGT2B7, and UGT2B15 for epirubicin glucuronidation. Only UGT2B7 converted epirubicin to its glucuronide. No differences in epirubicin glucuronidation were found in HK293 cells expressing the two UGT2B7 variants at position 268. Catalytic efficiency (V(max)/K(m)) of epirubicin glucuronidation was 1.4 microl/min/mg, a value higher than that observed for morphine, a substrate of UGT2B7. Formation of epirubicin glucuronide was significantly related to that of morphine-3-glucuronide (r = 0.76, p0.001) and morphine-6-glucuronide (r = 0.73, p0.001). No correlation was found with SN-38, a substrate of UGT1A1 (r = 0.04). UGT2B7 is the major human UGT catalyzing epirubicin glucuronidation, and UGT2B7 is the candidate gene for this phenotype. The reported tyrosine to histidine polymorphism in UGT2B7 does not alter the formation rate of epirubicin glucuronide, and undiscovered genetic polymorphisms in UGT2B7 might change the metabolic fate of this important anticancer agent.

Flavopiridol, a cyclin-dependent kinase inhibitor currently undergoing clinical evaluation, has a dose-limiting toxicity of diarrhea. Preclinical data on flavopiridol metabolism indicate that flavopiridol undergoes hepatic glucuronidation. The purpose of this study is to evaluate whether the occurrence of diarrhea is related to the systemic glucuronidation of flavopiridol. Parent drug and metabolite concentrations in plasma were measured by high-pressure liquid chromatography in 22 metastatic renal cancer patients treated on a Phase II trial of 50 mg/m2/day of flavopiridol administered every 2 weeks as a 72-h continuous infusion. Pharmacokinetics of flavopiridol and its glucuronide were assessed during the first cycle at 23, 47, and 71 h during the infusion. Flavopiridol concentrations at 23, 47, and 71 h were 389 nM (296-567 nM), 412 nM (297-566 nM), and 397 nM (303-597 nM) [median (interquartile range)], respectively. Flavopiridol glucuronide reached a plateau of 358 nM (196-553 nM) at 47 h. Metabolic ratios of flavopiridol glucuronide:flavopiridol at 71 h showed an apparent bimodal distribution with an antimode of 1.2. Thirteen patients experienced diarrhea and had lower metabolic ratios [0.72 (0.53-0.86)] than patients without diarrhea [2.24 (1.76-2.3); P = 0.002]. Eight of 11 extensive glucuronidators (ratio1.2) did not develop diarrhea, whereas 10 of 11 poor glucuronidators (ratio1.2) developed diarrhea (P = 0.008). The glucuronidation of flavopiridol is apparently polymorphic, suggesting a genetic etiology. The systemic glucuronidation of flavopiridol is inversely associated with the risk of developing diarrhea.

A moderated 252 Cf source to be used for the detection of buried land mines has been experimentally characterised. The moderating structure was obtained by using an inner sphere of Pb embedded in a high-density polyethylene (HDPe) brick assembly. The number of capture events in a Cd sample placed outside the structure was used, by varying the dimensions of the brick assembly, to determine the best moderator geometry. Furthermore, the detection of land mines by neutron capture reaction on nitrogen nuclei contained in the explosive was simulated by in field measurements placing the Cd sample at different depths in the soil. The obtained results are compared with predictions from Monte Carlo calculations.

To the Editor: The possible association between hepatitis C virus (HCV) infection and B-cell–type non-Hodgkin's lymphoma (NHL) has previously been suggested.[1-4][1] HCV tropism for hepatocytes and also, according to recent data, for the salivary gland ductular cells[5][2] may imply the existence

Age has proved to be an important prognostic factor in patients with advanced non-Hodgkin lymphoma (NHL) and these patients require intensive and extensive therapy. Dose-reduction and therapy attenuation have reduced treatment-related toxicity, but have also decreased therapeutic efficacy. Between January 1990 and December 1992, 41 previously untreated patients, 65 years with stage 2-4 intermediate- or high-grade NHL were treated with a new therapeutic scheme which included Mitoxantrone, Etoposide, Cyclophosphamide and Prednisone (MiCEP). Twenty-eight patients achieved a complete remission, ten patients partial remission (overall response rate of 93%) and two cases were resistant. The overall survival was 66% with a median follow-up of 24 months from diagnosis: three patients relapsed after a median period of 7 months. The relapse-free survival was 92% after a median follow-up of 18 months. Blood and other organ toxicity was acceptable and 12% of patients experienced a grade 4 (WHO) neutropenia. In conclusion, MiCEP was effective in inducing a good remission rate with moderate toxic effects in elderly patients with intermediate- or high-grade NHL and appears to be a useful combination to use in this group of patients.

Introduction Since the early days, liver transplantation (OLT) has conquered several barriers worldwide to become a proven therapy. We assessed the evolution of our adult liver transplant program. Methods We studied all adult patients who underwent OLT since the inception from November 1993 through May 2003. Donor data, recipient pretransplantation evaluation, surgical technique, results, and costs were examined over our evolution, stratifying 3 groups over time, based on the number of adult OLT per year. Results Between November 1993 and May 2003, 70 OLT were performed in 64 patients older than 15 years of age. Preoperative Child score, preoperative creatinine level, donor and recipient age, and proportion of emergencies were similar in the 3 groups. Over time, the predominant surgical technique was the piggyback technique (97% of OLT) with a decrease in the use of bypass from 63% to 5% during the last time period. Over the 10 years of our program's existence, warm ischemia time has been reduced to less than 1 hour, whereas cold ischemia time has remained constant at around 5 hours. Biliary and vascular complications decreased over time to around 10%. The mean length of hospital stay (LOS) decreased to 12 days (excluding emergencies). Since inception, our 1-year patient survival rate average is 91%; however, in just the last 3 years of our program (2000 through 2003), the 1-year patient survival rate is 97%. Conclusions In summary, our surgical technique has evolved toward piggyback use without veno-venous bypass with a significant decrease in warm ischemia times. As expected, our results have improved over time and our LOS and costs have decreased. Finally, our current results are similar to the best ones reported in the medical literature today.

Summary Diabetes, hypercholesterolemia, hypertension, obesity, osteopenia, and increased risk of viral recurrence are among the complications associated with posttransplant steroid use. Steroid withdrawal or rapid taper has been reported to be safe. The aim of this study was to compare the rejection incidence and severity among patients treated with two different steroid taper strategies. Methods This retrospective study included all the adult liver transplant recipients since the program's inception from 1993 to January 2002. The minimum follow-up was 1 year. Exclusions included patients receiving an immunosupressive regimen other than mycophenolate mofetil, steroids, and Neoral, or suffering an autoimmune etiology, or displaying patient or graft survival less than 1 year. The incidence and severity of rejection episodes were compared between the two groups of steroid taper protocols: group A received methylprednisolone (1 g) intraoperatively with a slow taper to 10 mg prednisone per day at 1 year. Group B received methylprednisolone (2 g) intraoperatively followed by a rapid reduction with intention to withdraw by month 4, continuing on Neoral monotherapy. Rejection diagnosis was made on histological bases. Results One-month and 1-year rejection rates were 47% and 53%, respectively, among the rapid taper group with Neoral monotherapy, which was similar to 60% and 64%, respectively, in the slow taper group. Rejection severity was also comparable between the two groups. Conclusions Patients treated with a rapid steroid taper protocol followed by Neoral monotherapy or a slow taper protocol showed similar acute rejection incidences and severities. Their survival rates were also comparable. Further study is necessary to evaluate the impact of rapid steroid taper to prevent the complications of steroid use.

Monoclonal antibodies against the interleukin 2 receptor have been developed in an effort to decrease rejection rates and spare calcineurin inhibitors when renal dysfunction occurs after transplant. While success has been reported in kidney transplantation, its effectiveness in liver transplantation is less clear. Methods This prospective nonrandomized study including adult patients was performed between October 2000 and April 2003. Two groups of immunosuppressive regimens were compared: group A received 2 g of methylprednisolone intraoperatively followed by a rapid reduction with intention to withdraw by month 4, continuing on Neoral monotherapy. Cellcept was also given for 2 months in the absence or for up to 4 months in the presence of rejection. Group B received the same immunosuppressive regimen but, in addition, daclizumab 1 to 1.5 mg/kg on day 1 and day 5 posttransplant. Rejection diagnosis is made on histology basis. Protocol biopsies were performed in all the patients on day 7 and if indicated by biochemistry thereafter. Results Both groups were similar in terms of preoperative CHILD score, serum creatinine, incidence of status I, donor and recipient age and ischemia times. The mean follow-up time was 20 months for Group B ( n = 24) and 7 months for Group A ( n = 10). The 1-month and 1-year rejection rates are 29.1% and 41% in Group A versus 20% and 30% in group B. Rejection severity was similar between both groups. One-year patient and graft survival rates were 96% and 92% in group A and 100% for both in Group B. Conclusions In this series, daclizumab induction therapy seems to display a trend toward a lower rejection rate without increasing infectious complications nor affecting graft survival rates.

Aim: To assess consistency between left ventricular (LV) wall motion modification and coronary flow reserve in the left anterior descending coronary artery (LAD) territory during dobutamine stress-echo (DSE). Methods: 173 patients underwent DSE, according to the standard protocol, for evaluation of known or suspected coronary artery disease and, during the test, LAD flow velocity was measured at baseline and at peak stress. Segmental kinesis was evaluated both for all LV segments then limited to LAD territory (aWMSI). Coronary flow reserve (CFR) was calculated as the ratio between peak stress and baseline maximal diastolic velocity in the distal LAD. In a subgroup of 48 patients, without anterior myocardial infarction (MI), accuracy of non-invasively evaluated RFC was verified with coronary angiography data. Results: Patients were predominantly males (122.71%), mean age was 68±11 years; 69% were hypertensive, 37% diabetics, 46% presented dyslipidemia and 53% were smokers. Fifty-two patients had a recent or previous anterior MI, in 30 treated with primary PCI. Baseline echocardiography showed normal LV internal dimensions (end-diastolic volume index 63±20 ml/m 2 ; endsystolic volume index 34±18 ml/mq), with slightly reduced LV global systolic function (ejection fraction 47±27%). During ESD, both global WMSI then aWMSI resulted significantly and negatively correlated with RFC at baseline, after low dose and high dose dobutamine infusion; a similar correlation was also present between RFC and WMSI changes during high dose infusion, indicating extension of inducible ischemia. After exclusion of patients with anterior MI, these correlations remained significant; in the group with anterior MI, CFR was significantly and negatively correlated only with aWMSI after high dose infusion. Considering the final results of DSE and dividing patients in no or mild ischemia and extensive inducible ischemia (more than three LV segments), there was a significant difference in CFR value between the two groups (1.82 vs 2.26, p