September 30 - October 1, 2011; Milan, Italy
The scientific organizer intended the conference to emphasize the contribution of young national and international scientists, whose selected abstracts were presented orally and were published as a special edition of the journal Placenta.
Innovative surgical procedures in ART
In his talk on ‘Gynaecological fertility sparing surgery’ G. Siesto (Italy) explained that cryopreservation of ovarian tissue may be the only acceptable method to preserve fertility for women who cannot delay the start of cancer treatment and also for women with hormone-sensitive malignancies. He described a study that demonstrated that the amount of well-preserved follicles and stoma cells was similar in the fresh and slow freezing/rapid thawing procedures.
T. Falcone’s lecture (USA) on robotic indications in reproductive surgery showed that the robotic approach has several advantages over traditional laparoscopy. Recent clinical research indicates that robotic surgery results in less postoperative pain, shorter hospitalization, faster return to normal activities and decreased blood loss. Innovative surgical approaches to endometriosis were discussed by E. Somigliana (Italy) who focused on two main aspects (i) preventing injury to the follicular reserve following surgical excision of ovarian endometrioma and (ii) preventing post-surgical formation and re-formation of adhesions using barrier agents and gel solution.
T. Tulandi (Canada) reviewed the literature on reproductive surgery. The main goal of reproductive surgery is to improve the live birth rate of ART and for fertility preservation, making use of minimally invasive techniques. Hysteroscopy is a valuable tool to evaluate the uterine cavity and to treat intrauterine pathologies. Hydrosalpinx reduces the IVF pregnancy rate. Removal of the hydrosalpinx by laparoscopy can improve pregnancy and live birth rates. Pregnancy rate can also be improved by proximal tube occlusion by hysteroscopy.
C. Bulletti described the impact of myomas on pregnancy outcome before and after myomectomy with and without ART programs. He showed how pregnancy rate after myomectomy is significantly increased.
In a keynote lecture, G. Scaravelli (Italy) examined the benefit and risk of application of European tissue management regulation in ART. The Directive’s objectives include the prevention of the spread of infectious diseases by avoiding viral transmission and microbial contamination during transplantation procedures of human organs, tissue and cells. Reproductive cells are included under this Directive and therefore ART centers have had to conform to these requirements. In the future it will be important to achieve a standardization of ART clinic activities in the EU in order to compare outcomes obtained in the different countries
Innovation in ART laboratories
L. Rienzi’s (Italy) lecture on new culture devices in ART explained how improvements in culture of pre-implantation embryos have contributed substantially to the success of human assisted reproductive techniques. Recently, intensive research has begun to provide a more appropriate environment for the embryos and to replace the rather primitive and inappropriate devices with more sophisticated and practical instruments such as microwells and microchannels that allow accumulation of autocrine factors and establishment of a proper microenvironment for embryos. Connection of these techniques to additional radical approaches such as automated or robotic ICSI or an ultimate assisted hatching with full removal of the zona pellucida after or even before fertilization may result in devices with high reliability and consistency.
M. Montag (Germany) discussed the scoring systems to assist in identifying the best embryo. Embryo morphology assessment is based on the subjective judgment of the embryologist and sometimes even a variety of different scoring systems for one and the same parameter do exist. Therefore it is not surprising that, for almost every scoring system, controversial results can be found in literature. With the recent introduction of time-lapse imaging which enables continuous embryo monitoring, some scoring criteria such as pronuclear and embryo morphology must be critically revised. Proper scoring is even more important when the aim is to transfer only one embryo.
The promises and pitfalls of oocyte and embryo metabolomics were the topic addressed by Z. P. Nagy (USA). He explained that, until recently, the only instrument used for embryo evaluation was the inverted light microscope, which provided information based on morphological characteristics but new types of measurement such as measurement of oxygen consumption by the embryo or amino-acid turnover are also able to provide valuable information regarding embryo viability. Proteomics and metabolomics are also useful tools for assessment of embryo developmental potential.
It was the lecture of R. Reijo Pera (USA) that stressed the use of non-invasive imaging of human embryos to predict competence. She explained that following the time-lapse imaging, key developmental features were extracted to generate an algorithm that predicts success or failure in development to the blastocyst stage. She showed results suggesting that success or failure in human development is inherited: embryos that begin life with defective maternal, cell cycle and/or mitotic programs are likely to meet aberrant cytokinesis, embryo fragmentation, non-uniform blastomere size and/or shape as well as arrest of individual blastomeres or the entire embryo.
Exploring the chaos: the early stages of embryo development
Microarray CGH is the key to understanding oocyte developmental competence according to D. Wells (UK) who showed how embryos with apparently poor morphological or metabolomic scores nevertheless succeed in producing healthy pregnancies. Consequently the data provided by such evaluations is not clear-cut. In contrast, a chromosomally abnormal oocyte will produce an embryo that has abnormalities in all of its cells and has little if any chance of producing a healthy child. To overcome the problem microarray comparative genomic hybridization (aCGH) was introduced. This permits the copy number of every chromosome to be determined in polar bodies, blastomeres and trophectoderm biopsies and shows great promise for the purpose of PGS.
J.R. Vermeesch (Belgium) explained that the finding of a large number of chromosomal imbalances in cleavage stage embryos challenges the view that cleavage stage embryo selection against chromosomal imbalances could increase IVF success rate and increase the baby-take-home rate in patients treated by IVF for reduced fertility. With the advent of genome wide SNP arrays it might also become feasible to use arrays as a tool to perform PGD in embryos to detect Mendelian disorders.
H. Van de Velde (Belgium) explained that many aspects of human pre-implantation development are unknown and must be extrapolated from animal models. Early mammalian blastomeres are thought to be flexible and totipotent allowing the embryo to overcome perturbations in its organization during pre-implantation development. The zygote is the ultimate totipotent cell, however it is unknown when and in which cells during the cleavage divisions totipotency is lost. Understanding human pre-implantation development and totipotency is important for reproductive biology, in particular to understand why some embryos implant and others do not.
J. Delhanty (UK) described the various approaches to pre-implantation genetic screening (PGS). A variety of cells may be chosen for testing: the first polar body, with or without the corresponding second polar body, a single blastomere from a cleavage stage embryo or a group of cells from the trophectoderm at the blastocyst stage.
P. Willems (Belgium) reviewed whole genome sequencing in a prenatal setting. The first network of diagnostic labs offering genetic tests was incorporated five years ago and is called GENDIA (GENetic DIAgnostics). This international network consists of genetic diagnostic labs with greater access to a large spectrum of genetic tests performed with higher quality and lower cost. In coming years, technological advances will soon make whole genome/exome sequencing commonplace in the medical environment and spark an expansion of both basic and clinical research in which millions of patients with illnesses will have their complete (coding) DNA sequenced. Unfortunately our ability to detect DNA variation has greatly outstripped our ability to interpret the impact of such variation on phenotype.
The session closed with the winner of the award for the best abstract published in the journal Placenta, with an oral presentation entitled ‘High resolution genome-wide array-CGH reveals copy number variation associated with premature ovarian failure’. The winner was P. Scaruffi from the Department of Obstetrics and Gynecology of Genoa (Italy). Six more oral presentations followed this first one showing the interest of the new generation in research and the science of human reproduction.
Present and future of ART
The process of obtaining consent may be more or less complex, depending on whose consent is sought and their understanding. F. Shenfield (UK) explained that the principles of consent may only be obtained after appropriate information is given in understandable terms. Particularly difficult problems concern how to assess the techniques which may be qualified as being ‘innovative’ for research only, or also used for therapy.
P. Patrizio (USA) presented a vision of IVF in the next five years, including new approaches to ovarian stimulation protocols such as mild stimulation or natural cycle and in vitro maturation (IVM), how to reduce the IVF inefficiency by selection of the competent oocyte or embryo, and new techniques for fertility preservation such as in vitro folliculogenesis or spermatogonial isolation. He also discussed the ethical dilemmas, the need to reappraise preconception screening for recessive disease, and stressed the continuing role of research and education.
The topic of fertility preservation (FP) was discussed by N. Noyes (USA). Nowadays the most utilized fertility preservation measures available to women are oocyte cryopreservation (OC), ovarian tissue cryopreservation (OTC) and in vitro maturation (IVM). In addition, for female cancer patients electing FP, ovarian transplantation (pre-radiation) and co-administration of GnRH analogues during gonadotoxic chemotherapy also exist, with limited usefulness. Therefore if there is an adequate time-window between cancer diagnosis and treatment, OC should be the FP measure most strongly considered as it currently provides patients with the greatest chance for future live-born outcome.
A. Arav (Israel) presented studies on lyophilization and rehydratation of cells. This technique has numerous advantages over freezing, including low-cost storage, light weight, ease of transportation, and simplicity of handling. It has been reported for example that freeze-dried mice spermatozoa were able to generate normal offspring following injection (ICSI) into mature mice oocytes and the ability of lyophilized hematopoietic stem cells derived from umbilical cord blood to proliferate and differentiate to different blood cells, showing new opportunities for lyophilization technique.
In the final keynote lecture, C. Simon (Spain) discussed endometrial secretomics and implantation. The endometrial secretome is known to contain a number of mediators which are the reflection of the endometrial receptivity status which may be involved in the pre-implantation of embryos. The last part of the session was dedicated to seven oral presentations chosen from the abstracts received. All the participants showed a deep interest in discussing controversial topics and methodologies of treatments.
December 1-2, 2011; Madrid, Spain
In his keynote lecture, L. Nardo (UK) discussed the definition and detection of poor response and pregnancy outcome. It is well known that adequate ovarian response to gonadotrophin stimulation is a prerequisite for successful in vitro fertilization (IVF). Consequently the definitions of a poor responder are varied, ranging from chronological age to suboptimal response to gonadotrophin stimulation in a previous IVF cycle, including the retrieval of very few oocytes (<3) or the retrieval of immature oocytes and cancellation for inadequate follicular development. Nardo’s lecture stressed, in particular, the fundamental difference between ovarian response and ovarian reserve, albeit that both have been associated with reduced pregnancy potential. The viability of biochemical and ultrasound markers of ovarian performance, including FSH, LH, anti-Müllerian hormone (AMH) and antral follicle count (AFC) is useful for counselling purposes and for individualization of stimulation protocols. After the lecture, case studies on this topic were presented and participants were able to debate the different clinical approaches. The cases studies emphasised that, in the case of poor responses, the physician should consider age, length of menstrual cycle, and AFC before choosing the ovarian stimulation protocol. The long protocol is often not the best choice and an antagonist protocol may improve the number of oocytes. After plenary discussion of several case studies, the participants were divided in three groups, in order to have a more direct interaction with the speakers. R. Fanchin (France) managed the topic of therapeutic perspectives for poor responders. The clinical management of patients presenting insufficient ovarian responsiveness to FSH depends on the adequate understanding of factors underlying the lack of response. Therefore, the number and reproductive competence of ovarian follicles as well as the status of their FSH receptors is still controversial. He suggested that possible improvements in the number of follicles entering the basal growth phase include artificially increasing intra-ovarian androgen production in order to increase the viability of ovary, as well as other approaches that may reduce the size discrepancies of antral follicles before ovarian stimulation, without curtailing endogenous gonadotropin production during FSH treatment. He also discussed the FORT theory (Follicle Output RaTe), a method to identify the qualitative marker of ovarian response. During the workshop on three-dimensional ultrasonographic ovarian vascularity and its prediction value in poor responders, Fanchin showed interesting video and images. Ultrasound technology has allowed the non-invasive assessment of ovarian vascularization, in particular stromal and peri-follicular perfusion. He showed a number of articles associated with stromal perfusion and response to ovarian stimulation and, of course, IVF-ET outcome. Ovarian perfusion presumably declines with ageing, and ultrasonographic analysis of perifollicular blood supply is likely to provide useful information on the reproductive status of ovarian follicles.
The second session began with the working group on management of poor response and optimization of ovarian stimulation protocols. A. La Marca (Italy) was supported by L. Nardo and J.A.G. Velasco in the three groups discussing different clinical cases. C. Simón (Spain) in the third keynote lecture discussed implantation. The embryonic implantation process needs a coordinated development and communication between chromosomally and functionally normal blastocyst and the receptive maternal endometrium. Implantation failure is associated with IVF failure in 10% of patients undergoing ART. He discussed the inefficiency of the implantation process in humans and presented an overview of his experience on the possible causes of implantation failure and the protocols used in the IVI centers to address this problem. Simón and his team have created a genomic tool called endometrial receptivity array (ERA) composed of a customized microarray and a bioinformatics predictor for endometrial dating in order to detect pathologies of endometrial origin. This topic was also the subject of the case studies following the lecture. Simón showed different clinical cases and different approaches to implantation failure. F. Bronet, chief of the laboratory in IVI Center, Madrid, discussed laboratory topics and techniques used in the IVI Madrid clinic, showing a video demonstrating the methodologies and different procedures. After the video the participants visited the laboratories to find out more about the laboratory techniques and procedures performed (Andrology laboratory and IVF Laboratory).
In the third session on laboratory techniques, N. Prados (Spain) presented a keynote lecture on OoSight and EmbryoScope. These are non-invasive imaging systems where the meiotic spindle of the oocyte can be visualized and also some structural characteristics of the zona pellucida can be detected. This allows a better knowledge of the oocyte quality especially before performing ICSI or polar body biopsy. The EmbryoScope is an incubator with an embryo time-lapse monitoring system which can track the embryos without disrupting the culture. It acquires images of up to 72 individual embryos during development instead of the standard evaluation of the morphology of the evolving embryo. By this method many parameters can be reported, such as the exact time of each division, the number of nuclei during the divisions or the number of cells after each division. These new technologies should provide higher implantation and pregnancy rates through better oocyte/embryo selection. N. Basile (Spain) showed a video of the mechanism of action of the time-lapse technology. Time-lapse evaluates pre-implantation embryo development, the exact timing of main embryo events such as cleavage to 2, 3 and 4 cells, among others. Preliminary data suggest that the timing of embryo cleavage may correlate with the viability of the embryos. Andrological tools to improve fertilization was the topic discussed by A. Pacheco (Spain), who described diagnostics tests and methods of spermatozoa selection. For example MSOME (high magnification motile sperm organelle) or IMSI (intracytoplasmic morphologically selected sperm injection) allowing the single microinjection of selected motile spermatozoa with strictly defined morphologically normal nuclei into the cytoplasm of retrieved oocytes. MACS (magnetic-activated cell sorting) is an excellent tool for separating apoptotic cells present in ejaculates from infertile patients. All of these new methodologies should improve fertilization outcome, but more studies are needed to support them.
B. Balaban (Turkey) and N. Prados (who replaced Gloria Calderon who was sick) discussed in a round table vitrification and slow freezing. These new methods of oocyte and embryo cryopreservation have raised many discussion points and a long debate on which is better and where technology will take us, in order to optimize cost-benefit and results. Both speakers agreed that vitrification has better results and offer excellent clinical outcomes, and the safety of the procedure has been confirmed by the obstetric and perinatal outcome assessment.
C. Rubio (Spain) discussed the controversial topic of pre-implantation genetic screening (PGS) and its usefulness. PGS is a variant of PGD applied to the screening of numerical chromosome anomalies in couples with normal karyotype but with infertility problems. PGS is used to discard affected embryos in carriers of monogenic diseases and structural chromosome anomalies; its current indications are: advanced maternal age, recurrent miscarriage, repetitive implantation failure and severe male factor infertility. The final keynote lecture on thrombophilia and treatments, was delivered by Y. Cheong (UK). There is currently little evidence to support universal screening for thrombophilia prior to IVF. Selective thrombophilia screening based on previous personal and/or family history of venous thromboembolism is more cost-effective than universal screening of all IVF patients. Thromboprophylaxis should be considered in women with a previous deep venous thrombosis, women who develop ovarian hyperstimulation syndrome and women over 40 with thrombophilia. In addition, women who develop serious infection or immobilization should receive thromboprophylaxis. More studies are needed to validate the treatment in IVF failure and recurrent miscarriages.
The conference ended with a roundtable discussion involving all the speakers from the previous sessions. The faculty debated the topics of the day with the participants, emphasizing that the topics of primary importance in ART in the future will include biomarkers, metabolomics, viability assessment of embryos, cryopreservation techniques and oocyte freezing for social reasons.
Presentations and abstracts will be available soon
December 7, 2011; Yokohama, Japan
Biomarkers of gamete and embryo quality
T. Takeuchi (Japan) discussed the topic of mithocondria and ooplasmic donation. Fertility declines with maternal age and this is particularly evident by an increased incidence of oocyte aneuploidy. It has been postulated that insufficient ATP production due to mithocondrial dysfunction is responsible for structural abnormalities of the meiotic spindle leading to malsegregation of chromosomes/chromatids in oocytes of older women. In his research, in order to assesss the effect of mithocondrial damage on meiotic maturation in germinal vesicle (GV) stage oocyte, a mithocondrial insult was imposed by specifically inhibiting the ATP production pathway, or by damaging mithocondria. The meiotic spindles of those treated oocytes were then examined by immunofluorescence. Dr T. Takeuchi developed a germinal vesicle technique (GVT) in order to prevent chromosomal defects associated with aged oocyte.
A. Tanaka (Japan) explained a new technology of oocyte plasmic exchange for aged oocytes. It is a common phenomenon that pregnancy rates decrease, but miscarriages increase, and the percentage of fetal chromosomal abnormalities in miscarriages increases according to female age, reaching > 90% with women who are over 40 years old. Nuclear transfer into the metaphase –II (M-II) oocyte shows promise as a means of repairing female infertility due to ooplasmic deficiency and abnormalities. He described his technique involving nuclear transfer of in vitro matured metaphase –II oocyte (recipient oocytes) into an enucleated freshly ovulated metaphase –II oocytes (donor oocyte). The M-II karyoplast was removed successfully in 35 of 41% (85,4%) of the donor oocytes and 40 of 48 (83.3%) of the recipient oocytes. It demonstrated that oocytes constructed following the karyoplast transfer of in-vitro matured M-II oocytes into enucleated freshly ovulated M-II oocytes, clearly had more efficient and chromosomally normal embryonic development than did in-vitro-matured oocytes after ICSI. This technique can be applied to the treatment of female infertility due to ooplasmic deficiency and abnormalities in aged oocytes. H. Leese (UK) discussed the topic of biomarkers in preimplantation embryos, focusing his lecture on metabolic markers especially amino acid profiling (APP). He reported studies from Sturmey et al showing that AAP offers the possibility of predicting prospectively the ability of single bovine zygotes to develop to the blastocyst stage. This study highlighted differences in profiles between male and female embryos, those derived in vivo and in vitro, and the influence of maternal nutrition. One explanation for these data is in terms of the ‘quiet embryo hypothesis’ which proposed that viable embryos have a ‘quieter’ metabolism than those which fail to develop. This study was developed also by Bauman et al, who speculated that those embryos with a quieter metabolism were subject to less damage to the genome, transcriptome and proteome, or were better equipped to deal with damage when it occurred and thus devoted fewer resources (such as amino acids) to the repair process. The last lecture of the session on pre-implantation specific genes was made by M. Ko (USA). Starting from studies on mouse, recently it has been shown that human preimplantation embryos undergo waves of gene activation starting from the 2-cell stage. In his lecture he provided a broad overview of gene expression regulation in mouse and human preimplantation embryos.
Screening methodologies
D. Albertini (USA) discussed the topic of oocyte and embryo quality in order to improve ART outcomes. The studies that he presented emphasized identification of parameters of cytoplasmic maturation necessary for embryonic development that might at some point be consistent with non-invasive biomarker testing at the level of the cumulus-corona cells. H. Abe (Japan) talked about oocyte and embryo selection based on oxygen consumption. Studies have demonstrated that mithocondrial activity is a ubiquitous parameter also used to gain valuable information on embryo quality. To evaluate the embryo quality he employed a scanning electrochemical microscopy (SECM) technique, in order to scan and monitor the local distribution of electro-active species near the sample surface by a microelectrode. Recently this technique has been improved in a modified SECM that includes a measuring instrument mounted on the stage of an inverted optical microscope, a potentiostat, and a notebook computer for component control and analysis. Oxygen consumption of individual embryos at different developmental stages is monitored. Furthermore, the embryos with higher oxygen consumption are better candidates to further development into good quality embryos and yielded higher pregnancy rates after embryo transfer. Concluding that the respiration activity correlates with the embryo quality. E. Seli (USA) reviewed embryo selection, from genetics to the ‘omics’. The limitations of morphologic evaluation of embryos have led many investigators to pursue adjunctive technologies for the assessment of the reproductive potential of a given embryo, with the aim of developing an objective, accurate, fast and affordable test. The final speaker of the session, N. Macklon (UK), discussed the topic of ovarian response and value of AMH. There is, in fact, interest in identifying factors that enable the prediction of response and thus appropriate selection of patients and of the individual dose likely to optimize treatment outcomes. Recently there has been increased interest in the use of AMH to help predict dosing regimens. In his slides he showed how cohort studies have shown that serum AMH levels can predict response to exogenous gonadotropins, and that it may provide the basis for a simple means of individualizing dose regimens in IVF. There has also been increased interest in pharmacogenetics as applied to ovarian response. A number of specific polymorphisms of the FSH receptor have been identified which affect the response to exogenous gonadotropins. However, he concluded that, before a prediction model can be introduced into every day clinical practice, prospective external validation is required.
Improving outcomes
This session on improving outcomes began with a lecture by A. Fukuda (Japan) on strategies for managing poor responders. Most aged female patients, especially older than 40 years, are considered poor responder. ART in Japan has unique difficulties in treating poor responders compared to others countries. In Japan it is possible to treat poor responder only by personal oocytes, because oocyte donation is not allowed by the guidelines of the Japanese Society of Obstetrics and Gynecology (JSOG). He showed that the percentage in his clinic of patients older than 40 years was 10,4% in 2005 but increased to 17,4% in 2011. The strategy they used for older patients was to freeze more than 3 embryos obtained after several trials of natural or mild stimulation IVF, and then transfer in a subsequent frozen-thawed embryo transfer cycle (FET). Another method used is in vitro maturation (IVM), which can be very effective when other methods do not achieve pregnancy. J. A. G. Velasco (Spain) explained how important it is nowadays to individualize the ovarian stimulation protocol for each patient and how this is part of the evolution of fertility treatment. Patients with no observable abnormalities, illness or abnormal laboratory test results may still be unable to conceive. For this reason, the availability of multiple new approaches to controlled ovarian stimulation (COS) is needed. These sub-fertile patients must be considered on an individual basis and treated with an individualized COS tailored to meet their specific needs. Y. Asada (Japan) stressed the importance of the AMH in daily clinical practice, in order to select the appropriate protocol for ART. Although AMH cannot be used to predict conception rates, its level is a very effective predictor of ovarian hyperstimulation syndrome (OHSS) and should be assessed to avoid side effects. The final lecture, given by N. Suzuky (Japan) on fertility preservation in cancer patients, presented the problem of decreased quality of life in young female cancer patients, due to early menopause or loss of fertility after remission. Chemotherapy and radiotherapy can cause loss of reproductive function in young women due to adverse effects such as ovarian failure. Ovarian stimulation to obtain ova is time-consuming and is sometimes considered a taboo depending on the type of cancer. It is often less than one month between the diagnosis of the underlying disease and the beginning of treatment, since chemotherapy cannot be delayed. These are the cases where cryopreservation of ovarian tissue is proposed for fertility preservation, raising the hope of a future pregnancy.
Presentations and abstracts will be available soon
September 30, 2011 - October 1, 2011; Florence, Italy
Anat Achiron spoke on the epidemiology of cognition disorders in MS, explaining that these disorders are largely under-diagnosed. They may occur very early in the course of the disease and can impact significantly on daily functioning. Detection of cognition disorders can involve a complex range of therapies and equipment and should start following screening very early in the course of MS.
The prevalence of cognitive impairment varies according to different cognitive domains and Dawn Langdon, in her lecture on neuropsychological patterns, reported that the severity of cognition disorders increases over time, following the disease’s progression. She also showed that prevalence of mild forms of cognitive impairment tends to increase markedly in the first years of the disease.
Maria Pia Amato, reviewed the cognitive issues in paediatric MS, and reported that Corpus Callosum and thalamic volume, assessed by MRI, show characteristic alterations in paediatric MS patients with cognitive impairments. She pointed out that baseline IQ is a significant factor in predicting cognitive impairment in these patients. Older age at onset also predicts cognitive deterioration in pediatric patients.
Plenary sessions alternated with interactive workshops where multiple choice questions and a voting system supported the discussion. John DeLuca chaired the first workshop on pathophysiology of cognition impairment. The interactive voting by participants inspired lively discussion. Answering a question about the area(s) of the brain usually associated with memory impairment, many participants indicated the hippocampus but John DeLuca explained that other areas are also involved but the hippocampus was the first area to be linked to this defect in the early 1990s. In his conclusions, he emphasized that environmental factors influence development of cognition disorders in MS.
Emilio Portaccio and Ugo Nocentini opened the interactive session on ‘Longitudinal studies and insights from genetics’ showing how longitudinal studies’ outcomes contribute to our understanding of the evolution of cognitive impairment in MS. They pointed out that the individual profile of cognition impairment is the result of the course of the disease, specific genetic background, environment and MS therapy.
In his lecture on psychometric assesment, Ralph Benedict explained that regulatory authorities provided guidance on patient-reported outcome measures. He discussed the range of analysing tests and batteries aimed to detect cognitive impairments, proposing advantages and disadvantages.
Conventional and advanced neuroimaging were covered in lectures by Massimo Filippi and Nicola Di Stefano. Conventional neuroimaging provides relevant information on relationships between brain damage and cognition impairment. The location of lesions appears to suggest that cognitive function has been impaired. MRI findings on thalamic fraction are related to the outcomes of main cognition tests. Nicola De Stefano outlined what could be the contribution of main advanced MRI techniques to cognitive disorders. Early assessment shows that both single MRI variables and composite MRI indexes correlate with cognitive tests. He concluded that a future relevant role of advanced MRI techniques will be the monitoring of cognitive rehabilitation outcomes.
Opening the workshop on assessment batteries, Bruno Brochet showed how cognitive impairment becomes an occupational impairment too in MS patients. When asked to give their view, most of the audience agreed that it was right to screen cognitive function in all MS patients.
Giancarlo Comi opened the second day of the symposium by reviewing the effects of current DMDs on cognition disorders.
John DeLuca explained the behavioural approaches used in rehabilitation of MS patients with cognitive impairment. He mentioned a 2008 review which analysed papers on cognitive rehabilitation according to evidence-based medicine criteria. The authors found that studies were affected by methodological problems limiting the reliability of outcomes. John Deluca also addressed rehabilitative approaches targeted to specific cognitive impairment. He concluded that new controlled clinical trials are needed to assess and compare efficacy of rehabilitation approaches.
Lauren Krupp spoke on pharmacological approaches to cognition disorders and the rationale to use them. She then reviewed the outcomes of major studies testing the efficacy of several molecules on cognition disorders and concluded that none of the drugs tested consistently improves cognition in MS based on primary outcome analyses.
John Deluca spoke on behavioural approaches. Workshops on ‘Immunomodulatory treatments and cognition’ and ‘new oral therapies’ were very well attended, with excellent discussions.
October 18, 2011; Amsterdam, Netherlands
Etiology and pathogenesis
Jan Hillert (Sweden) described an important recent large genome-wide association study that identified several genes central to MS pathology. The theme of risk factors was taken up by Alberto Ascherio (USA), who reviewed how geographical location and migration, cigarette smoking, Epstein-Barr virus infection and vitamin D intake affect the risk of MS.
Christine Stadelmann-Nessler (Germany), provided an update on recent developments in the understanding of the mechanisms of demyelination, axonal damage and remyelination and the correlations with clinical signs of MS. Hans-Peter Hartung (Germany) then gave a thorough overview of the cellular and molecular mechanisms behind MS immunopathogenesis.
Diagnosis
Xavier Montalban (Spain) detailed the clinical use of the 2010 update to the McDonald criteria in diagnosis of MS. Letizia Leocani (Italy) then highlighted the utility of evoked potentials in diagnosis and monitoring of MS. The use of MRI techniques was described by Frederik Barkhof (The Netherlands), who explained their use in differential diagnosis of MS, determining pathophysiological features of MS and monitoring disease progression.
Treatment
Considering the issues involved in treating MS, Fred Lublin (USA) highlighted some of the common shortfalls in MS symptom management and highlighted the many ways in which we can improve our patients’ lives by treatment of symptoms such as spasticity and fatigue.
Mark Freedman (Canada) explored the available disease-modifying drugs, posing questions on how we might measure and compare the efficacy of the present array of available treatments. Each disease-modifying drug has its own set of potential adverse effects, a fact highlighted by Gavin Giovannoni (UK), who stressed the need to balance the benefits of treatment with the potential risks to the patient. The broad range of available treatments was further discussed in the presentation by Giancarlo Comi (Italy), who pointed out that various treatment approaches are possible, and that treatment should be tailored to the individual patient’s needs.
Jerry Wolinsky (USA) looked to the future and pointed out the apparent differences between historical clinical trial populations, and those of contemporary trials. He then summarised the latest data available for several agents that may soon be available for the treatment of MS.
October 18, 2011; Amsterdam, Netherlands
Colleen Harris (Canada), introduced the MS Nurse Club, of which she is a member of the Editorial Board. The MS Nurse Club, which will be launched by SSIF in 2012, is a new educational project which aims to develop online tools and to create an MS nurse network.
Improving organization and optimizing treatment
Mark Freedman (Canada) emphasised that MS is a complicated disease, and patients have complex problems that require a multidisciplinary approach. Nurses play a key role in managing MS patients and the social workers’ contribution is increasing to support them.
Dawn Carle (Canada) described the role of the nurse in centers managing clinical trials. Patient selection is a key factor in the success of a clinical trial and requires teamwork where collaboration between doctor and nurse is crucial. Fred Lublin (USA) discussed the available disease-modifying treatments and reminded delegates of the pharmacological treatments developed in recent decades. He also pointed out that, while several pharmacological treatment options are available for RRMS, the progressive forms of MS still lack effective disease-modifying treatments.
The interactive voting following the first session showed that nurses are very conscious of the unique role that they play in supporting patients. Answering a question on how to proceed when a first line drug fails to reach treatment goals, a combination of well-known drugs to enhance treatment efficacy was the most voted-for solution compared with a switch to a newer and less well-known drug.
Interaction with MS patients
Yoram Barak (Israel) discussed the psychological and social impact of MS diagnosis, an important issue that healthcare professionals have to deal with. He pointed out that the time elapsing between the appearance of the first MS symptom or sign and the confirmation of diagnosis is a critical period for the patient.
Jaume Sastre-Garriga (Spain) examined was of encouraging adherence to treatment in MS patients. He described the scenario facing healthcare professionals and MS patients and suggested ways to improve interaction. Diane Lowden (Canada) also considered adherence to treatment but from the nurses perspective. Claudio Gasperini (Italy) and Amy Perrin Ross (USA) gave two talks on 'at home assistance', also from the perspectives of the doctor and the nurse respectively.
Cognitive and psychological issues
Maria Pia Amato (Italy) reviewed the main studies performed to evaluate cognitive function impairment in MS patients and the outcomes of studies on the effects of DMDs on cognitive impairment. Monica Falautano (Italy) addressed cognitive rehabilitation and Giancarlo Comi (Italy) underlined that changes in mood, personality and cognition are among the most disabling symptoms for MS patients. Dawn Langdon (UK) showed how the nurse and the cognitive behavioural therapist may have synergistic approaches in managing MS patients’ psychological problems.
Motor and genito-urinary problems
Alan Thompson (UK) pointed out that, even though MS has a low prevalence, its management implies very high costs. He then explained why it is very difficult to apply the evidence based medicine (EBM) approach in assessing rehabilitation procedures. Urs Gamper (Switzerland) showed some impressive video on rehabilitation techniques used to treat spasticity. Oscar Fernandez (Spain) and Roberta Motta (Italy) closed the symposium addressing urinary disorders.
November 7-9, 2011; Barcelona, Spain
At the beginning of the meeting, the MS Alumni Program, a brand new educational project dedicated to young physicians in the field of MS was announced. This program aims to create a lasting community – starting by involving the MS Preceptorship delegates - to share ideas and best practice well into the future through live and online activities that will be published on a dedicated micro-site within the SSIF website. The project will involve three main European MS centers: Multiple Sclerosis Centre of Catalonia, Cem-cat, Barcelona, Spain Institute of Experimental Neurology, Vita-Salute San Raffaele University, Milan, Italy Valens Clinic Rehabilitation Center, Valens, Switzerland
In collaboration with each one of these centers, e-learning activities will be implemented and three live preceptorships with different focuses on MS will be organized in 2012.
Day 1
Beginning with the first lecture on MS epidemiology and risk factors, delivered by Susana Otero (Spain), the audience was involved in lively discussion addressing intriguing aspects such as the relationship between the social and political focus on MS, and changing epidemiological findings. Manuel Comabella (Spain) then delivered the first of his two presentations addressing MS genetics. He emphasized in particular a recent study published by an international consortium. As usual, the core faculty of this preceptorship was composed of Cem-Cat staff members, together with some ‘guest stars’ chosen from the top experts in the field in order to provide participants with the most up-to-date knowledge about key topics.
Heinz Wiendle (Germany) and Wolfgang Brück (Germany) addressed the different ‘scenarios’ of MS immunopathogenesis and the heterogeneity of gray and white matter damage.
A panel discussion, chaired by Oscar Fernandez (Spain) and including Mar Tintoré (Spain), Alex Rovira (Spain) and Letizia Leocani (Italy) as panellists, debated optimization of the use of diagnostic tools.
In the early afternoon session, Carmen Tur and Georgina Arrambide, both from Cem-Cat (Spain) presented case studies that stimulated lively discussions with the audience. The visits to Cem-Cat premises closed the first day of the course.
Day 2
The specific forms of demyelinating diseases were addressed by Alejandro Horga (Spain), Alan Thompson (UK) and Angelo Ghezzi (Italy). Jaume Sastre-Garriga (Spain), one of the scientific organizers, gave a talk on symptom management, one of the main clinical issues in MS. Carmen Santoyo and Marta Renom, both from Cem-Cat (Spain), closed the session with two presentations on gait rehabilitation and dysphagia management.
A panel discussion chaired by Alan Thompson was dedicated to cognition disorders in MS, and Maria Pia Amato (Italy) and Maria Jesus Arevalo (Spain) addressed, respectively, diagnostic tests and rehabilitation, and pharmacological treatments. A case study presented by Angela Vidal (Spain) provided a further opportunity to discuss this important aspect.In her keynote speech Eva Havrdovà (Czech Republic) reviewed the cornerstones of treatment protocols and algorithms. Rosalia Horno (Spain) described the role of nurses in MS Centers before a lively case study session followed by a new round of visits allowing participants the chance to discuss organizational issues with Cem-Cat staff members working in the different premises.
Day 3
The final day began with a panel discussion on the definition of treatment success, which is an increasingly important topic in the real-world scenario of MS management, where several new treatment options are being introduced into clinical practice. Mar Tintoré was the chair of this session and Jordi Rio (Spain) and Manuel Comabella the two panellists. A role-play session involving a doctor, Jaume Sastre-Garriga, a psychologist, Maria Jesus Arevalo, and a patient provided participants with a unique opportunity to analyse issues of interaction between healthcare professionals and patients, and to discuss solutions. Xavier Montalban (Spain) and Giancarlo Comi (Italy) delivered the following two lectures on oral drugs and monoclonal antibodies respectively. These lectures provided outstanding overviews of present and future MS treatments. Three short communications on gene therapy, vaccines and stem cells were presented before Xavier Montalban’s ‘wrap-up’, which highlighted some of the course's main contents.
December 12, 2011; Shanghai, China
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Antony Shapira (UK) reviewed the prodromes of PD. Early diagnosis is on of the top priorities in PD management today, and understanding of prodromes is crucial for early detection. Professor Schapira outlined the factors,that have been shown to increase the risk of developing PD; these include red hair, low vitamin D intake and employment as doctor or teacher. He then reviewed PD genetics and pathophysiological mechanisms and suggested that some of the molecules involved in the latter can be used as possible biomarkers for early diagnosis. Antony Shapira concluded by showing how symptoms are related to progression of neurodegenerative processes and he emphasized the relevance of hyposmia, depression, REM sleep disorders and constipation as prodromes of PD.
Erik Wolters (The Netherlands) defined motor dysfunctions in PD and illustrated these symptoms with videos. He then discussed the relationships between synucleinopathy diffusion and motor symptom appearance, referring also to the Braak classification to define severity. In order to explain the extreme complexity of PD’s clinical features, he showed how other neurological systems, besides the dopaminergic system, are affected in PD: glutamatergic, GABAergic, norepinephrinic, serotonergic and cholinergic systems can all be altered. A comprehensive understanding of the role of these systems could, in the future, provide promising therapeutic targets.
Jeffrey Kordower (USA) discussed stem cells and gene therapy. He explained why the scenario is clearer now, after many years when the hopes for the possible advantages of stem cell transplantation had not been balanced by careful consideration of issues implicit in this approach. He then reviewed the main gene therapies under investigation and showed that animal studies are providing information on the effects of trophic factors targeted at delivering on damage evolution and symptoms.
Presentations and abstracts will be available soon
October 27-28, 2011; Buenos Aires, Argentina
The basic principles of pharmacogenomics were introduced by Dr Lilien Chertkoff (Argentina) who explained how drug response, represented by efficacy and toxicity, mainly depends on individual genetics. Pharmacogenomics, by using genome-wide association studies, simultaneously evaluates such genes, identifying polymorphisms linked to diverse drug-response profiles. Already in use in some disease (i.e. cancers), this approach can help in personalizing drug therapy with better outcomes.
Dr Miguel Constância (UK) discussed epigenetics, phenomena by which a gene can have different expressions and biological effects. Modifications in DNA and RNA differ between subjects, also occurring in genes linked to diseases and drug response and are possible targets for intervention. Nutrients can affect gene expression too, with maternal diet influencing expression of developmental genes in the foetus and predisposing it to diseases.
Alternative splicing was discussed by Dr Anabella Srebrow (Argentina) who explained how it affects RNA formation by copying the DNA of the genes differently, resulting in different RNAs and proteins function. Extracellular and environmental factors (e.g. diet) can influence such processes. Alternative splicing affects over 60% of genes and causes malignancies and over 50% of mutations in human genetic diseases, so it is a potential target for therapeutic options.
Dr Miguel Constância (UK) presented mouse studies of altered growth in which genes of the GH-IGF1 axis and others seem implicated, like in humans. Over 265 genes are involved in placental and foetal growth, their mutation or different expression influencing placental size and its adaptation to foetal demand, growth and metabolism when adult. Targeting such genes in humans could influence both growth and metabolic diseases.
Dr Nora Saraco (Argentina) discussed alternative splicing occurring in the aromatase, enzymes transforming androgens in estrogens, differently expressed and regulated in several tissues including bone. Various congenital mutations in different regions of the single gene copy generate variants of its RNA giving inactive proteins. Understanding the molecular basis of such defects can help in approaches to novel therapies.
Growth and metabolic disorders
Dr Pinchas Cohen (USA) summarized the results of studies on the use of GH therapy in children with idiopathic short stature and in GH or IGF1 deficiencies. The final GH dose depended on the degree of hormone deficit and resistance, but maximal results in final height were obtained while titrating the dose to IGF1 levels appropriate for age (+1SDS), in particular when doubling the recommended GH dose.
The PREDICT study examined genetic markers predicting responses to GH therapy in children with GH deficiency and Turner syndrome, by using SNP analysis of 103 genes of the GH-IGF1 and other pathways. Dr Pierre Chatelain (FRA) discussed the study and showed that some polymorphisms correlated with 1-month IGF1 response and also with catch-up height at 1 year. Genetic profiles and early IGF1 levels can help monitoring and implementing therapy.
Dr Alexander Jorge (BRA) discussed a cohort of Brazilian patients with Noonan syndrome having at-birth malformations, delayed puberty and postnatal short stature. Several gene mutations explain over 75% of cases. Long-term GH therapy induced a relatively normal final height, whilst a lower body mass index was observed when adult, indicating a possible alteration in metabolism and energy storage.
Dr Saroj Nimkarn (USA) described 21-hydroxylase deficit in adrenal glands causing false precocious puberty, increased bone age, and deficit of final height in over 50% of patients. Corticosteroids and gonadotropin releasing hormone agonists given to delay puberty can also cause deceleration of growth velocity. GH therapy started prior to puberty and continued for a long period, can improve final height up to quite normal stature.
Further 1- and 2-yr results of the PREDICT study in children with GH deficiency and Turner syndrome were given by Dr Pierre Chatelain (FRA). Some polymorphisms in genes of the hypothalamic-pituitary axis, bone growth plate and cell cycle correlated with achievement of certain final height at the given time points. Genetic profiles, auxological, hormonal and metabolic factors can predict and guide GH therapy.
Dr Veronica Mericq (Chile) defined insulin resistance in children as a state of subnormal substrate metabolism having certain insulin levels. Very high or low weight at birth but also excessive weight recover, especially in first 3 months, high BMI, obesity, and polycystic ovarian syndrome can present insulin resistance. No clear cut-off levels exist to define it, the many indexes available to measure it not being reliable for screening use.
Dr Pinchas Cohen (USA) outlined the role of humanin and humanin-like small peptides, from mitochondrial genes. In rodents they showed antiapoptotic, anti-inflammatory and hypoglycaemic properties, preventing neuronal degenerative diseases and diabetes, also reducing atherosclerosis and improving endothelial dysfunction; cell-cycle modulation in cancer development and growth disorders was observed. Human studies are warranted.
Clinical cases
Drs Prieto and Domené (Argentina) showed a case of severe growth deficit and immune depression. GH was normal but there was no response of IGF1 to GH generation test, outlining GH resistance. A novel missense mutation in STAT5b gene was found to be responsible, producing an inefficient protein at post-receptorial level of GH signal. IGF1 therapy, possibly early in life or prior to puberty, is recommended.
The case of a child with severe short stature at birth, microcephaly and mental retardation was presented by Drs Aziz and Guercio (Argentina). GH was normal while IGF1 was very high, outlining IGF1 resistance. A new spontaneous mutation in just one allele of the IGF1 receptor gene was found to be responsible through production of a non-functional protein. GH therapy showed some beneficial effects on head size and height.
Presentations and abstracts will be available soon
November 4-5, 2011; Santiago, Chile
Biological targets in the treatment of cancer
Bernardo Garicochea (Brazil) presented the role of epigenetics and looked at targets in the neoplastic cell, cell receptors and signal transduction. He reviewed treatment options using drugs that can suppress the function of epigenetic enzymes, particularly methylation of DNA cytosine residues and histone deacetylation. Used singly, such drugs have limited efficacy in haematological malignancies but may prove more useful when used together. He explained that microRNAs have a role in gene regulation and represent an important target for future therapy. Wolfgang Berdel (Germany) focused on the role of angiogenesis in cancer, which is a multistep process that can be inhibited at several stages. Neo-angiogenesis is limited mainly to wound healing in the healthy adult, but carcinomas depend on vessel generation for their growth. Vascular endothelial growth factor (VEGF) plays a key role in neo-angiogenesis and appears to have a prognostic value in various cancers. Carlos Silva (Argentina) looked at the role of immunotherapy in cancer treatment, including the use of preventive and therapeutic vaccines. There is now a wide range of newly identified potential tumor antigens that could be targeted by vaccines. Sipuleucel-T is the first approved therapeutic cancer vaccine and has been used successfully in prostate cancer. Other new immunotherapies include ipilimumab, an IgG1κ anti-CTLA-4 monoclonal antibody, recently approved for the treatment of patients with unresectable or metastatic melanoma. Hernán Lupera, (Ecuador) ended the first session with a talk on mechanisms of resistance to targeted therapies, which are many and varied.
The changing approach to treating cancer
Luis Contreras (Chile) highlighted the advances in molecular diagnosis, which have provided a better understanding of the genesis of human tumours and enabled the development of targeted therapy. Salvatore Siena (Italy) described the increasing number of biomarkers that guide targeted cancer therapy across a range of tumours. KRAS was the first biomarker prospectively shown to predict non-response to epidermal growth factor receptor (EGFR) monoclonal antibody treatment in metastatic colorectal cancer (CRC). Jorge León Chong (Peru) described the clinical biomarkers that play a role in the diagnosis, classification, prognosis and treatment of haematological malignancies. Drugs such as imatinib, a tyrosine kinase (TK) inhibitor, have dramatically improved the 10-year survival of patients with chronic myeloid leukaemia.
Clinical applications: from the lab to the clinic
The molecular treatment of neuroendocrine tumours was the topic covered by Jose Luis Aguilar Ponce (México). Current guidelines recommend that well differentiated carcinoid tumours of the intestine are treated with a somatostatin analogue or VEGF inhibitor, and that pancreatic cancer is treated with an mTOR (mammalian target of rapamycin) inhibitor or multiple TK inhibitors and cytotoxic chemotherapy. Recommended treatment for poorly differentiated tumours of both tumour types is a platinum agent plus etoposide.
Rachel Riechelmann (Brazil) reviewed the molecular treatment of CRC, which is a heterogenous group of diseases, targets for which include thymidylate synthase, microsatellite instability, KRAS/BRAF, VEGF and PI3K (phosphoinositide 3-kinase)/AKT/mTOR. She concluded that genetically different tumours require tailored medicines, for example BRAF mutations can be treated with MEK inhibitors, and PI3K mutations or PTEN (phosphatase and tensin homolog) loss with perifosine. Clarissa Mathias (Brazil) talked about the molecular treatment of lung cancer. She discussed first- and second-line and maintenance treatment of advanced non small cell lung cancer (NSCLC) and future prospects for therapy. In first-line therapy, bevacizumab, a VEGF inhibitor, improves survival when added to cisplatin chemotherapy in patients with non-squamous NSCLC.
The molecular treatment of head and neck cancer was presented by Carlos Canela (Venezuela). Squamous cell carcinoma of the head and neck (SCCHN) can be divided into human papilloma virus (HPV) positive and negative diseases, which are two distinct entities. Biomarkers for SCCHN include p53, pRb, p16, cyclin D, EGFR and survivin. Elizabeth Mickiewicz (Argentina) talked about the molecular treatment of breast cancer. To date the best studied agents targeting biomarkers are HER2/neu antibodies. For HER2 positive disease, targeted treatments in development include inhibitors of TK, VEGF, mTOR, heat shock protein 90, and P13K. In HER2 negative disease, molecular targets include the PI3K/Akt/mTOR pathway.
The molecular treatment of melanoma was discussed by Gabriela Cinat (Argentina). Targeted therapy against the BRAF/mitogen-activated protein kinase pathway is a promising new treatment approach for this tumour type. The meeting closed with a look into personalized medicine by Salvatore Siena who concluded that truly individualized treatment of cancer was impractical in clinical practice, but that the way forward was the development of targeted therapies that had good clinical efficacy and good therapeutic indices.
Key slides and abstracts will be available soon
November 25, 2011; Rome, Italy
In the first session ‘Assessing cardiovascular risk by traditional and emerging risk factors’ coordinated by Ettore Ambrosioni and Mohsen Ibrahim, Samir Arnaout discussed the guidelines and risk calculators. He underlined that previous guidelines in Europe were based on global risk factors. LDL cholesterol is still the primary target in the management of patients with dyslipidemia, but unlike the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines, the European task force provides less flexibility in interpretation.
The second lecture by Vasilios Kotsis was focused on obesity and metabolic syndrome. This important risk factor develops from the interaction between the genotype and the environment and involves social, behavioural, cultural, physiological, metabolic and genetic factors. The relationship between obesity and hypertension is well established in children and adults. Obese individuals exhibit higher levels of office and ambulatory blood pressure and non-dipping status.
The third lecture, presented by Guido Grassi, focused on the evidence that has emerged over the past 20 years to underline the prognostic role of the elevated heart rate in cardiovascular diseases. In essential hypertension, several reports have shown the potential significance of an elevation in heart rate in determining fatal and non-fatal cardiovascular events. In this presentation, evidence for heart rate prognostic value was discussed and it was emphasised that heart rate adrenergic overdrive represents a risk factor for cardiovascular diseases.
Eyas Al Mousa remarked the role of inflammatory markers. For example c-reactive protein (CRP) is related to cardiovascular risk and levels below 1mg/l are considered low risk. Also the combination of calcium score assessment by CT scan with biomarkers index have recently been proposed as markers of risk.
Enrico Agabiti Rosei discussed the target organ damage in hypertensive patients. It was remarked that 2003 ESH-ESC Guidelines underlined that diagnosis and management of hypertension should be related to quantification of global cardiovascular risk. The 2007 ESH-ESC Guidelines have further emphasized the importance of assessing the presence of subclinical target organ damage (TOD). An extensive evaluation of TOD may increase the number of patients classified at high CV risk and therefore strongly influence the clinical management of patients.
During the second session ‘Controversies in the treatment of diabetic patients with CAD’, coordinated by Joseph Rendon and Ghaida Kaddaha, Peter Nilsson focused on reduction of macro- and microvascular complications by anti-diabetic treatment and HbA1c goal.
In this session Giuseppe Mancia reported that conclusive evidence is available to show that, in hypertensive patients, blood pressure (BP) reduction by drug treatment reduces the incidence of fatal and non-fatal cardiovascular (CV) events, and that, to maximize CV protection, BP values < 140/90 mmHg (systolic/diastolic), and perhaps even < 130/80 mmHg need to be achieved if CV risk is high.
In the following lecture, Omar Hamanoui, remarked how lipid lowering therapy has become the backbone of cardiovascular risk reduction with numerous, large clinical trials proving its benefit in a broad array of clinical conditions.
Finally in this session Ettore Ambrosioni, underlined that cardiovascular diseases (CVD), the first cause of death worldwide, cost the European Community more than 169 billion of euro/year. Clinical trials have provided definite evidence that blood pressure (BP) can be controlled using appropriate drugs with a decrease in both morbidity and mortality. But in clinical practice, in the large majority of hypertensive patients BP remains uncontrolled even in those who were diagnosed and treated: in 60–70 % of patients BP levels are above140/90 mmHg.
In the last session ‘Focus on atrial fibrillation’ coordinated by Massimo Volpe and Saeed Al Saeed, Samer Ellahham presented atrial fibrillation (AF) as one of the most common sustained serious cardiac arrhythmia associated with significant morbidity and mortality.
The second lecture of this session was given by Josep Redon, in order to present strategies for secondary prevention of stroke. In fact, he remarked that stroke survivors are at increased risk of recurrent stroke and other ischemic vascular events, and face significant cross-risk for atherothrombotic conditions affecting the coronary and peripheral vascular beds. As such, the secondary prevention of ischemic events in patients with stroke has focused on the treatment of atherosclerosis as a whole, with antihypertensive treatment, lipid-lowering drugs and anti-platelet therapy playing a key role.
Nidal Asaad, discussed atrial fibrillation and remarked that over 6 million Europeans suffer from this arrhythmia, and that its prevalence is predicted to at least double in the next 50 years as the population ages. He remarked that guidelines summarize and evaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best management strategy for an individual patient suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic approaches.
Finally Adel Khalifa, underlined the role of vitamin K antagonists such as warfarin, which reduce the risks of stroke by approximately two-thirds but at the same time increase the risk of hemorrhage.
The last session was devoted to discussion of clinical cases in order to simulate real-world clinical practice. During this session, Giuseppe Mancia and Joseph Sebastian Vallavanthara conducted an interesting discussion with the audience.
The first case presented by Azan Bribrek was related to a young patient with myocardial infarction with low level of LDL-c, the second case was presented by Ghaida Kaddahe and referred to a diabetic nephropathic patients, and the last was presented by Hassan Chamsi-Pasha and focused on resistant hypertention. All these cases were useful to understand how to apply guideline for prevention and treatment of cardiovascular risk factor in high risk patients.
The audience participated actively, by an electronic vote system in order to share opinions about how to approach the cardiovascular risk, both for prevention and treatment.
Presentations and abstracts will be available soon
Annual meeting in multiple sclerosis
(May 18-19, 2012; Valencia, Spain) ... More information
Satellite symposium at ENS (European Neurological Society)
(June 11, 2012; Prague, Czech Republic) ... More information
MS Preceptorship - Updating knowledge in multiple sclerosis
(June 5-7, 2012; Barcelona, Spain) ... More information
Preceptorship on rehabilitation in multiple sclerosis
(September 20-22, 2012; Valens, Switzerland) ... More information
Conference in multiple sclerosis
(September 14-15, 2012; Cartagena, Colombia) ... More information
Preceptorship on MRI in multiple sclerosis
(October 2012; Milan, Italy) ... More information available soon
MS Academia - Multiple sclerosis advanced course
(October 9, 2012; Lyon, France) ... More information
14th International MS Nurse Workshop
(October 9, 2012; Lyon, France) ... More information
Workshop on ultrasound in obstetrics gynecology (in partnership with University of Siena)
Siena, Italy
January 27/28, 2012
February 24/25, 2012
March 30/31, 2012
April 27/28, 2012
May 25/26, 2012
June 29/30, 2012
September 28/29, 2012
Course on Quality Management System (QMS) in ART
(February 23, 2012; Beijing, China)
The multi-factorial equations of ART: Defining and maximizing success in pregnancy rates
(May 18-19, 2012; Sorrento, Italy)
Born in/after ART: from the laboratory towards the delivery room (during the 11th World Congress in Fetal Medicine)
(June 24, 2012; Kos, Greece)
Advanced course in human reproduction and embryology (Pre-ESHRE)
(June 30, 2012; Istanbul, Turkey)
IVF Preceptorship: current practice in the 21st century
(September 27-28, 2012; Madrid, Spain)
2nd Dietitians Workshop on PKU
(March 22, 2012; Rome, Italy) ... More information
4th European Phenylketonuria Group (EPG) Symposium: Advances and challenges in PKU
(March 23-24, 2012; Rome, Italy) ... More information
7th Asia Pacific Medical Evaluation Workshop on Molecular Targeted Therapy of Cancer
(March 16-17, 2012; Bangkok, Thailand)
8th MTTC German Workshop
(March 23-24, 2012; Berlin, Germany)
13th MTTC International Workshop
(May 4-5, 2012; Saint Petersburg, Russia)
PKU Academy and PKU Masters
