European Study Groups Research Articles

Standardized MRD quantification in European ALL trials: Proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18–20 September 2008

Assessment of minimal residual disease (MRD) has acquired a prominent position in European treatment protocols for patients with acute lymphoblastic leukemia (ALL), on the basis of its high prognostic value for predicting outcome and the possibilities for implementation of MRD diagnostics in treatment stratification. Therefore, there is an increasing need for standardization of methodologies and harmonization of terminology. For this purpose, a panel of representatives of all major European study groups on childhood and adult ALL and of international experts on PCR- and flow cytometry-based MRD assessment was built in the context of the Second International Symposium on MRD assessment in Kiel, Germany, 18-20 September 2008. The panel summarized the current state of MRD diagnostics in ALL and developed recommendations on the minimal technical requirements that should be fulfilled before implementation of MRD diagnostics into clinical trials. Finally, a common terminology for a standard description of MRD response and monitoring was established defining the terms 'complete MRD response', 'MRD persistence' and 'MRD reappearance'. The proposed MRD terminology may allow a refined and standardized assessment of response to treatment in adult and childhood ALL, and provides a sound basis for the comparison of MRD results between different treatment protocols.

The evaluation of novel chromogenic substrates for the detection of lipolytic activity in clinical isolates ofStaphylococcus aureusand MRSA from two European study groups

Eight novel chromogenic substrates were evaluated for their efficacy in detecting lipase activity in clinical isolates of Staphylococcus aureus from the United Kingdom and Malta. All isolates metabolized the chromogenic lipase substrates 5-(4-hydroxy-3,5-dimethoxyphenylmethylene)-2-thioxothia-zolidin-4-one-3-ethanoic acid (SRA)-propionate, SRA-butyrate, SRA-octanoate and 2-[2-(4-hydroxy-3,5-dimethoxyphenyl)-vinyl]-3-methy-benzothiazolium salt (SB(Z)TM)-acetate. Over 90% of the isolates metabolized the lipase substrates SRA-decanoate and SRA-laurate. However, only 0.6% of UK isolates and 2% of Maltese isolates metabolized the lipase substrate SRA-myristate; none of the isolates tested metabolized SB(Z)TM-butyrate. Traditional Tween 80 assays showed that over 73% of the UK methicillin-resistant Staphylococcus aureus (MRSA) isolates and 83% of the UK methicillin-sensitive Staphylococcus aureus (MSSA) isolates demonstrated lipolytic activity. In contrast, Maltese isolates showed lipase activity in 94% and 88% of the MRSA and MSSA strains, respectively. Lipases in MRSA and MSSA demonstrated substrate specificity whose activity appeared dependent upon hydrocarbon chain length of the chromogen. These novel chromogens can be used for lipase enzyme detection and have application for full characterization of numerous S. aureus lipases.

The Prognostic Value of JAK2 Exon 16 Mutations in Children with Down Syndrome and Acute Lymphoblastic Leukemia.

Children with Down Syndrome (DS) have an increased risk of developing leukemia, including both acute myeloid (ML DS), as well as acute lymphoblastic leukemia (DSALL). Recently, Izraeli et al. reported on an activating mutation (R683) localized in exon 16 of the Janus Kinase 2 (JAK2) gene, in 18% of DS-ALL (n=16) patients collected from 9 European study groups (ASH 2007). Screening of other leukemia subsets showed that this mutation was exclusive for DS-ALL patients. This JAK2 mutation differs from the V617F exon 14 mutation found in myeloproliferative diseases. JAK2 is located on chromosome 9p24, and belongs to a family of intracellular non-receptor protein tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. It plays an important role in regulating the processes of cell proliferation, differentiation and apoptosis in response to cytokines and growth factors. Between 1991 and 2007, 45 children with DS ALL were treated in the Netherlands, according to the DCOG protocols ALL 7–10. Of 36 children samples were available in the DCOG cell bank, on which we performed JAK2 mutation screening of the pseudokinase and kinase domains of JAK2 by direct sequencing. All 36 patients were classified as BCP-ALL. Mutations in JAK2 exon 16 were identified in 6 (16.6%) DS-ALL patients. In five patients a point mutation resulted in substitution of Arginine at position 683, the same as was described by Izraeli et al. In one patient an insertion was found. JAK2 mutated patients did not differ in age at diagnosis (3.3 vs. 5.1 years, p=0.08) or in sex (p= 0.8) compared to non-mutated DSALL patients. The diagnostic WBC for DS-ALL patients with a JAK2 exon 16 mutation was lower than for non-mutated patients (3.6×109/L vs. 12.1×109/L; p=0.04). Ploidy status based on karyotyping was known in 29/36 patients. None of the JAK2 mutated samples was hyperdiploid (>52 chromosomes) vs. one in the non-mutated samples (p=0.89). TEL/AML rearrangements were screened in 23/36 samples, and 3/23 (13%) samples showed a TEL-AML rearrangement. None of the JAK2 mutated samples was TEL-AML rearranged (p= 0.76). One JAK2 mutated patient had a normal karyotype, the other JAK2 mutated patients had random cytogenetic abnormalities. We next analyzed the prognostic significance of JAK2 mutated DS-ALL children versus the other patients. The median follow up time for all patients was 3.1 years (range 0.1–15.1 years). Interestingly, none of the JAK2 mutated patients relapsed, versus 4/30 wild type JAK2 patients. The differences between pOS (100% vs. 83.3% p=0.41), pEFS (100% vs. 80%, p=0.38) and pDFS (100% vs. 82.8%, p=0.44) were not statistically significant, probably due to small numbers. Since DS-ALL children are more sensitive to the side effects of chemotherapy, and have relatively high toxic mortality rates, reduction of therapy intensity might be an option for DS-ALL children with a JAK2 exon 16 mutation, if our results could be confirmed in larger series. The development of specific JAK2 inhibitors may allow further reduction of chemotherapy.

First European Chemotherapy Schedule for Elderly Patients with Acute Lymphoblastic Leukemia: Promising Remission Rate and Feasible Moderate Dose Intensity Consolidation

Only few elderly ALL patients are entered to prospective trials and the data on patient characteristics and outcome are scarce. The European Working Group for Adult ALL (EWALL), which was funded in 2001 by all major national European study groups for adult ALL, therefore focused on the development of rational treatment approaches for elderly ALL as an unmet medical need. The group agreed on a chemotherapy backbone mainly based on elements derived from previous French and German protocols for elderly ALL. After a pre-phase with dexamethasone +/− cyclophosphamide the 4-week-induction comprised dexamethasone (10 mg/m2, d1–2,8–11), vincristine (1 mg, d 1,8), idarubicine (10 mg, d 1–2,8–9) in phase I and cyclophosphamide (500 mg/m2, d15–17) and cytarabine (60 mg/m2, d16–19, 23–26) in phase II. Consolidation consisted of 6 alternating cycles with 3 times methotrexate (1000 mg/m2, d1) and E.coli asparaginase (10000 U/m², d2) and 3 times high-dose cytarabine (1000 mg/m2/q12 hrs, d1,3,5) followed by maintenance with mercaptopurine, methotrexate and vincristine/dexamethasone pulses for a total treatment duration of 2 yrs. Dose reductions were recommended for pts older than 70 yrs, and slight modifications were made in the three participating countries. In a separate protocol the backbone chemotherapy is used in combination with Dasatinib for pts with Ph/BCR-ABL+ ALL. Between 1/07 and 8/08 54 pts with Ph-negative ALL from 33 centers were treated, and 40 pts were evaluable for response after induction (France 20, Germany 13 and Spain 7). The median age was 66 (56–73) yrs with 22% older than 70 yrs. General condition (ECOG) was 2–3 in 23%. 65% had c/pre-B-ALL, 15% pro-B, 17% T-lineage and 1 pt biphenotypic ALL. Cytogenetics (N=30) were normal in 40%, t(4;11) in 7%, complex in 7% and with other aberrations in 47%. 23% had WBC above 30000/μl at diagnosis. 34 (85%) pts achieved CR after induction. PR or failure was observed in 7% resp. No pt died during induction. 85% of the pts were alive at a median follow-up of 8 mo. The probability of survival after 1 year is 61%. 4/34 CR pts were withdrawn in CR from further treatment (12%). Of the remaining 30 CR pts 23 are in CCR (77%), 1 died in CR due to fungal septicaemia (3%), 6 relapsed (20%). The probability of continuous CR after 1 year is 49% with a median remission duration of 9 mo. During induction I and II the majority of pts experienced grade III–IV adverse events (AE), most frequently cytopenias (>90%) and infections (16% phase I, 25% phase II). Treatment with HDMTX/ASP (Cons I or III) was evaluable in 44 cycles. 45% were associated with grade III–IV AE, most frequently cytopenias, infections, liver disturbance and allergy to asparaginase in 2 pts. HDAC (Cons II or IV) was evaluable in 34 cycles with 47% grade III–IV AEs, again mostly cytopenias. With this age adapted induction regimen for elderly pts (median age: 66 yrs) a high CR rate (85%) was achieved. The moderate intensity consolidation treatment was tolerable, and the low rate of treatment related death elucidates the fact that intensive supportive treatment e.g prophylaxis/treatment of infections can be successful in elderly pts. It is noteworthy that treatment with asparaginase as a major drug for ALL, which was so far rarely used in elderly pts, was feasible as well. Although follow-up is short, the survival probability of 61% after 1 year is promising. In future trials new investigational drugs will be added to the backbone in order to evaluate their efficacy and feasibility in randomised studies. Partly supported by the European Union (European Leukemia Net)

Whence and Whither the PfP Consortium?

The PfP Consortium is already a full ten years old. The time has come to look back on the road it has traveled, and to anticipate what lies on the road ahead. This essay will dwell upon the most significant achievements of the Consortium (in my eyes), as well as upon some shortcomings. In doing so, it is useful to reflect on the notion of “PfP.” This shorthand method of referring to both partnership and peace obscures the meaning of these two very powerful words. As a “Partnership,” the Consortium requires the input of a variety of actors, and in this regard the support staff at the Marshall Center deserves most of the credit, as do the countries that have been generous with both their funding and logistical support over the years. Clearly, the United States, Switzerland, Germany, and Austria deserve most of the credit here. But the notion of “Peace” brings into focus the actions of those countries, institutions, and individuals for whom the Consortium was intended. The PfP nations of ten years ago—many of whom are now members of NATO and/or the EU—have been indirectly led into the larger process of integration through the willingness of their institutions to interact with partner institutions in other countries. For the directors and project managers in these academies, institutes, and ministries, this has required an inordinate amount of faith and moral courage. Discovering and displaying the moral courage necessary to shed the established views and the momentum of habits of fifty (if not (seventy) years of Cold War has been difficult indeed, even on the “Western” side of the equation. In this respect, the successes that have been achieved are partial, but still significant. In the case of the South East Europe, the catastrophe brought on in the Balkans by the disintegration of the former Yugoslavia had to be stopped by UN and allied intervention on two occasions since the end of the Cold War, in Bosnia and Kosovo. But this did not keep representatives from various factions from meeting in the halls of Reichenau Castle every spring (at the workshops held by the PfP Study Group on “Regional Stability in South East Europe”) to discuss, mostly constructively, the challenges of peace. Although the actors present at these meetings rarely had the power or authority to enforce any decisions that might have arisen from the spring discussions in Austria, an indirect influence was achieved by demonstrating what decades of peace could achieve, with the right mix of civic responsibility, tolerance, and accountability. Looking at the success of the Regional Stability in South East Europe Study Group, I do believe that we can identify certain elements of success. The first element is the commitment of a nation to host such an event in a recurring, predictable manner, championed by an expert team of organizers, and also supported by actors from the re-

Study groups in Denmark: A tale of three cities

AbstractSince 1998 European Study Groups have been held in Denmark, and Danish companies from LEGO and NOVO to very small high‐tech firms have participated. Here, I briefly describe the history, the organization and the format of the Danish Study Groups, and highlight a few problem solutions. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Resection alone in 58 children with limited stage, lymphocyte‐predominant Hodgkin lymphoma–experience from the European network group on pediatric Hodgkin lymphoma

Lymphocyte-predominant Hodgkin lymphoma (LPHL) is a rare, CD20-positive, good prognostic lymphoma in children. Patients with early-stage LPHL who underwent successful surgical lymph node resection alone have been reported. To clarify the optimum treatment strategy in children, European study groups were asked to report their experience of surgery alone used in the treatment of pediatric LPHL. Data from 58 patients were collected by the French Society for Pediatric Cancers, the German-Austrian Pediatric Study Group/German Society of Pediatric Oncology and Hematology (Germany), and the Children's Cancer and Leukaemia Group (United Kingdom). In total, there were 50 boys and 8 girls, and the median age was 11 years (age range, 4-17 years). Fifty-four patients had stage IA disease, 2 patients had stage IIA disease, and 2 patients had stage IIIA disease. With a median follow-up of 43 months (range, 2-202 months), the overall survival rate was 100%, and the progression-free survival (PFS) rate was 57%. Fifty-one of 58 patients achieved complete remission (CR) after surgery. In the CR group, the overall PFS rate was 67% (95% confidence interval, 51-82%). All seven patients who had residual disease after initial surgery developed recurrences (P = .003). Among 18 patients with stage IA LPHL who developed recurrent disease, 11 patients had local recurrences, and 7 patients recurred in stage IIA. One patient with stage IIIA disease presented with high-grade B-cell non-Hodgkin lymphoma at 10 years of follow-up. When complete resection was achieved, a substantial proportion of patients with surgically treated, early-stage LPHL experienced long-term remission and actually may have been cured.

Xenoandrogenic Activity in Serum Differs across European and Inuit Populations

BackgroundAnimal and in vitro studies have indicated that human male reproductive disorders can arise as a result of disrupted androgen receptor (AR) signalling by persistent organic pollutants (POPs). Our aim in the present study was to compare serum xenoandrogenic activity between study groups with different POP exposures and to evaluate correlations to the POP proxy markers 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p′-DDE).MethodsWe determined xenoandrogenic activity in the serum fraction containing the lipophilic POPs but free of endogenous hormones. Adult male serum (n = 261) from Greenland, Sweden, Warsaw (Poland), and Kharkiv (Ukraine) was analyzed. Xenoandrogenic activity was determined as the effect of serum extract alone (XAR) and in the presence of the synthetic AR agonist R1881 (XARcomp) on AR transactivated luciferase activity.ResultsThe study groups differed significantly with respect to XARcomp activity, which was increased in the Inuits and decreased in the European study groups; we observed no difference for XAR activity. We found the highest level of the AR antagonist p,p′-DDE in Kharkiv, and accordingly, this study group showed the highest percent of serum samples with decreased XARcomp activities. Furthermore, the percentage of serum samples with decreased XARcomp activities followed the p,p′-DDE serum level for the European study groups. No correlations between serum XAR or XARcomp activities and the two POP markers were revealed.ConclusionsThe differences in XARcomp serum activity between the study groups suggest differences in chemical exposure profiles, genetics, and/or lifestyle factors.

Surgical Resection Alone in Children with Limited Stage Lymphocyte Predominant Hodgkin's Lymphoma - The Experience of the EuroNet-PHL Group.

Introduction: Lymphocyte predominant Hodgkin's lymphoma (LP) is a rare CD20-positive subtype of Hodgkin's lymphoma which was only recently recognised as a separate disease entity. Most patients present with localised stage IA or IIA disease and usually, the disease has a relatively indolent clinical course. Up until recently, children with LP were treated alike classical Hodgkin's lymphoma and received chemotherapy +/− radiotherapy. Two published reports of surgical resection alone in 19 children with LP (Pellegrino 2003, Murphy 2003) suggest that this may be an effective therapeutic option for a select group of children with limited stage disease. Study objectives: Can a proportion of children with limited LP be cured by surgery alone if resection is complete? Is a watch and wait strategy after surgery alone safe for those patients with residual disease after resection? What is the risk of relevant upstaging at relapse and of transformation into an aggressive B-cell lymphoma?Methods: European study groups participating in the EuroNet-PHL inter-group were requested to report their experience of surgery alone in children with LP. Surgery as single treatment modality has been used on a case by case basis for several years by the SFCE (France), the DAL / GPOH (Germany), and more recently by the UKCCSG (UK). Individual data of 57 patients were collected using a common CRF. 11 cases already published by Pellegrino were updated and are included.Results: 49 patients with initial stage IA achieved a CR after surgery. In 8 patients (5 in IA, 1 in IIA, 2 in IIIA) resection was incomplete. At a median observation time of 43 months (max. 172 months) all patients are alive. In the CR group 13 relapses were observed, all occurring early within 26 months of resection. Freedom from progression is estimated to be 67% (95% CI [59%; 75%]). Of the 8 patients who had incomplete resection 6 patients relapsed (p=0.008), of whom one (initial stage IIIA) relapsed as non-Hodgkin lymphoma. Of the 16 stage IA patients who experienced a relapse, 9 had a local relapse alone and the remaining 7 relapsed with stage II A. The rate of upstaging (B-symptoms or relapse stage > II) was 0% (95%-CI: [0%; 21%]).Conclusion: If complete resection is achieved, a substantial proportion (about 2/3 in our series) of surgically treated stage IA patients experience long-term remission and may be actually cured. Nevertheless, as most of the relapses occurred in the initially involved lymph node region, a better evaluation of the remission status after surgery may be obtained if FDG-PET is combined with CT/MRI. Based on these data we have designed a Europe-wide study in FDG-PET-negative stage IA-IIA LP to prospectively confirm these promising results in a larger cohort.

Wilms' tumor and neuroblastoma

Significant differences exist between the European and North American treatment protocols for Wilms' tumor and neuroblastoma. There are variations in biopsy technique, timing and extent of initial surgery, chemotherapy protocols and dosage routines, as well as the type of salvage therapy. With the consolidation of the two major North American study groups into a single entity (Children's Oncology Group), the European and North American study groups represent the only remaining large-scale venues for treatment comparison. It is important to study and understand the variation in treatment protocols in order to maintain an open forum of scientific investigation that will lead to improving the care and outcome of children with cancer. It is anticipated that the unification of the North American groups will lead to greater interest and scientific cooperation with the European study group. This paper will serve as a forum for such a discussion at a local level.

Higher arterial oxygen saturation during submaximal exercise in Bolivian Aymara compared to European sojourners and Europeans born and raised at high altitude

Arterial oxygen saturation (SaO2) was measured at 3,600–3,850 m by pulse oximetry at rest and during submaximal exercise in three study groups: 1) highland Aymara natives of the Bolivian altiplano (n = 25); 2) lowland European/North American sojourners to the highlands with at least 2 months of acclimatization time to 3,600 m (n = 27); and 3) subjects of European ancestry born and raised at 3,600 m (n = 22). Aymara subjects maintained ∼1 percentage point higher SaO2 during submaximal work up to 70% of their maximal work capacity, and showed a smaller rate of decline in SaO2 with increasing work compared to both European study groups. The higher-exercise SaO2 of Aymara compared to Europeans born and raised at 3,600 m suggests genetic adaptation. The two European study groups, who differed by exposure to high altitude during their growth and development period, did not show any significant difference in either resting or exercise SaO2. This suggests that the developmental mode of adaptation is less important than the genetic mode of adaptation in determining exercise SaO2. A weak correlation was detected (across study groups only) between the residual forced vital capacity (FVC) and the residual SaO2 measured at the highest level of submaximal work output (P = 0.024, R = 0.26). While firm conclusions based on this correlation are problematic, it is suggested that a part of the higher SaO2 observed in Aymara natives is due to a larger lung volume and pulmonary diffusion capacity for oxygen. Results from this study are compared to similar studies conducted with Tibetan natives, and are interpreted in light of recent quantitative genetic analyses conducted in both the Andes and Himalayas. Am J Phys Anthropol 113:169–181, 2000. © 2000 Wiley-Liss, Inc.

Cancer prevention

Cancer prevention

Survival of AIDS patients according to type of AIDS-defining event. The AIDS in Europe Study Group.

There are known to be wide differences in the prognosis of patients with a diagnosis of AIDS. In this study of 6578 patients with AIDS form 17 European centres, we develop a ranking of AIDS-defining illnesses, and determine how well this ranking holds after adjustment for potential confounding variables. Survival from each AIDS-defining event was calculated and ranked using Kaplan-Meier estimation of median survival. Cox proportional hazards models with each disease modelled as a time dependant covariate were used to determine the risk of death after each diagnosis, before and after adjustment for potential confounders. Median survival after an initial AIDS-defining diagnosis of progressive multifocal leukoencephalopathy and malignant lymphoma was particularly poor (2 and 5 months respectively), while the longest median survival occurred after initial AIDS-defining illnesses of Kaposi's sarcoma and extrapulmonary tuberculosis (17 and 22 months respectively) Patients diagnosed with a primary brain lymphoma had shorter median survival times than patients with a peripheral lymphoma (median survival of 1 month and 4 months respectively P < 0.0001). In general, median survival in patients with cutaneous Kaposi's sarcoma (skin, oral) was between two and four times longer than patients with systemic involvement The ranking of diseases was found to be generally similar after adjustment for all potential confounders. AIDS-defining events can be grouped into three categories with median survival after diagnosis of < 6 months. 6-12 months and > 12 months. The assigned ranking of disease would not be altered by prognostic factors such as age or CD4 lymphocyte count. These results have important implications in the design of clinical trials and patient management.

Survival of European patients with Kaposi's sarcoma as AIDS-defining condition during the first decade of AIDS. AIDS in Europe Study Group.

To determine whether the survival of patients with Kaposi's sarcoma as first manifestation of AIDS has changed between 1979 and 1989; and to define whether prognosis factors could be identified. This is a multicentric retrospective cohort study from 52 centers in 17 European countries involving adults AIDS patients diagnosed between 1979 and 1989. Variables such as age, sex, geographical regions, transmission groups, date of Kaposi's sarcoma diagnosis, zidovudine use, CD4+ cell count and concomitant opportunistic infections or AIDS-related malignancies were evaluated by using uni- and multivariable proportional hazard models. Log-rank tests were used to determine which variables were associated with survival. From the 6,546 AIDS patients recruited in the database of the AIDS in Europe Study Group, 1,394 were diagnosed with Kaposi's sarcoma at the time of AIDS diagnosis, from 1979 and 1989. A total of 1,047 Kaposi's sarcoma patients died during the follow-up period. By Kaplan-Meier analyses, the median and mean survival for these Kaposi's sarcoma patients were 17 and 25 months, respectively, with no change over time. However, age, sex (female), geographic region, low CD4+ cell count (< 150 x 10(6)/l) and some opportunistic infections and non-Hodgkin's lymphoma were associated with a poorer prognosis. Zidovudine use, year of diagnosis and risk factor for HIV-1 infection brought no additional information as predictor of mortality. This study suggests that the survival of patients with Kaposi's sarcoma as first manifestation of AIDS has remained poor during the last decade in contrast with the overall AIDS survival which had significantly improved from a median of 13-18 months during the same period of observation. There is a need for further prospective information to explain the worse prognosis in women and the geographical variations.

8th European Congress of Clinical Microbiology and Infectious Diseases Lausanne, Switzerland, May 25--28, 1997.

On behalf of the committees of the 8th ECCMID, I would like to invite you to join us in making the May ′97 gathering in Lausanne a great success, a goal we feel will be realised by the combination of an outstanding scientific programme and the late-May dates of the Congress, a time of year when both the climate and the scenery should be at their best. The preliminary scientific programme we have planned thus far will include the best scientists in the various fields. This will be possible because the 8th ECCMID will be the major congress of its kind in Europe in ′97. The programme will begin in the morning with two simultaneous State-of-the-Art lectures, followed by parallel symposia. From 12.30 to 15.00 hours, the time will be devoted to the posters and the industrial exhibition. We have made a special effort to offer all participants a dynamic platform for exchange. This is underscored by a new type of session entitled “Meet-the-Speakers Sessions” which will take place after each symposium. These informal sessions will be scheduled during lunch and tea time. Thus, the programme will be smooth and relaxed, giving ample opportunities for meeting colleagues and engaging in interactive discussions. The Scientific Committee has obtained the support of several national and international societies such as the International Society of Infectious Diseases, the International Immunocompromised Host Society, Infectious Diseases Society of America, the Interscience Conference on Antimicrobial Agents and Chemotherapy Program Committee, the Centers for Disease Control and Prevention, the World Health Organization, the United Nations Programme on HIV/AIDS, the International Union against Tuberculosis and Lung Disease, the European Society of Paediatric Infectious Diseases and the European Society of Intensive Care Medicine. Joint symposia have already been organised with them or are being planned. Moreover, the European study groups and working parties of ESCMID have prepared special symposia presenting the most recent advances and discussing the major issues in their respective fields. Accreditation for continuing medical education is being sought in countries where applicable. In the United Kingdom, the Royal Colleges have agreed to an allocation of 15 hours, for full attendance. In Belgium, the Ministry of Health has accepted an accreditation of 150 points of Continuous Education. In the United States, the approval of the American Medical Association (AMA PRA Category 1 credits) is expected within the next few weeks. In order to make your stay on the beautiful Swiss Riviera as pleasant as possible from the outset, a welcome desk will be set up at Geneva Airport on Sunday, May 25, and special transfers to the Lausanne Congress Centre will be organized. Throughout the entire Congress, a free-of-charge, personalised transportation system will take participants from their hotels to the Congress Centre and back. An exciting social and artistic programme will begin with the Opening Ceremony, presenting the “Fête des Vignerons”, a major local event celebrating the vine, which has been held four times each century since the Middle Ages. The Opening Ceremony will be followed by a reception with free buffet and drinks as well as dancing. In the following days, the participants will have a choice between a free concert at the Lausanne Cathedral or a performance of the Béjart Ballet. Thus, we believe that, not only the scientific programme, but also the social and artistic events, will be of the highest quality and originality. We, therefore, invite all scientists from Europe and abroad, who are active in the field of clinical microbiology and infectious diseases, to join us in Lausanne from May 25 to May 28, and to submit abstracts. We are all looking forward to seeing you in Lausanne.

Streptokinase increased mortality in acute ischemic stroke

TherapeuticsJanuary 1, 1997Streptokinase increased mortality in acute ischemic strokePhilip Bath, MDPhilip Bath, MDKing's College School of Medicine & Dentistry London, England, UK (P.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-1997-126-1-002 SectionsAboutFull Text ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinkedInRedditEmail Source CitationThe Multicenter Acute Stroke Trial—Europe Study Group. Thrombolytic therapy with streptokinase in acute ischemic stroke. N Engl J Med. 1996 Jul 18;335:145-50.References1 Multicentre Acute Stoke Trial-Italy (MAST-I). Lancet 1995;346:1509-14. Google Scholar2 Donnan GA, Davis SM, Chambers BR, et al. Lancet. 1995;345:578-9. Google Scholar3 Hacke W, Kaste M, Fieschi C, et al. JAMA. 1995;274:1017-25. Google Scholar4 The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med. 1995;333:1581-7. Google Scholar5 Wardlaw J, Yamaguchi T, del Zoppo G, Hacke W. The Cochrane Database of Systematic Reviews. 1996; Issue 3. Google Scholar Author, Article, and Disclosure InformationAffiliations: King's College School of Medicine & Dentistry London, England, UK (P.B.) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails January 1, 1997Volume 126, Issue 1Page: 2KeywordsCerebral arteriesComputed axial tomographyDeath ratesHemorrhageHeparinInfarctionIschemiaIschemic strokeMyocardial infarctionSafetyStrokeSurgery ePublished: 9 March 2020 Issue Published: January 1, 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.Loading ...

Epidemiology of AIDS-related Kaposiʼs sarcoma in Europe over 10 years

To determine the incidence and risk factors associated with Kaposi's sarcoma (KS) occurrence as an AIDS-defining condition or after the diagnosis of AIDS. Multicentre retrospective cohort study of AIDS in Europe database from 52 clinical centres in 17 European countries. Patients' charts (n = 6546) were reviewed and collected in the database of the AIDS in Europe Study Group from 1979 to 1989. At the time of AIDS diagnosis 1394 patients had KS, whereas an additional 525 others developed KS after AIDS diagnosis. Univariate analysis and development of multivariate models determined factors associated with KS occurrence. Frequency of KS as an AIDS-defining condition significantly declined over time (P < 0.0001). In our cohort of patients, homo-/bisexual men from central Europe with CD4 cell counts > 150 x 10(6)/l were statistically more likely to develop KS at the time of AIDS diagnosis (P < 0.0001). For patients with an AIDS diagnosis other than KS, the probability of developing KS during the follow-up was 10 and 24% after 12 and 36 months, respectively. Variables significantly associated with a further KS development were transmission group, central European residence, previous herpes simplex infection other than ulcers, and low CD4 cells (< 150 x 10(6)/l). Previous zidovudine therapy had no influence on KS appearance. For patients who developed KS subsequent to AIDS diagnosis, there was no significant decline of the incidence over the 10-year time period. This large cohort study clearly shows that demographic data such as sex, transmission group and region of Europe have a major influence on KS development. It also suggests that KS as an AIDS-defining disease occurs earlier in the course of the chronic HIV infection than other opportunistic diseases. Reasons for geographical variations and its declining frequency as an initial AIDS diagnosis remain undetermined.

Comparison of long-term prognosis of patients with AIDS treated and not treated with zidovudine. AIDS in Europe Study Group

To determine the association between elapsed time since starting zidovudine and survival in patients with acquired immunodeficiency syndrome (AIDS). Inception cohort and observational study of patients treated and not treated with zidovudine. Fifty-one centers in 17 European countries. A total of 4484 patients diagnosed as having AIDS from 1979 to 1989 who survived their initial AIDS-defining event and who had not started zidovudine before AIDS diagnosis. Use of zidovudine and mortality. Among patients who did not receive zidovudine, the death rate was approximately constant for the first 5 years after AIDS diagnosis. For patients treated with zidovudine, the death rate within the first year since starting zidovudine was markedly lower than for untreated patients who had developed AIDS at the same time (relative rate, 0.47; 95% confidence interval [CI], 0.42 to 0.51). For longer times since starting zidovudine, the association with reduced mortality rate was diminished, and for patients surviving more than 2 years since starting zidovudine, the death rate was greater than for untreated patients who had developed AIDS at the same time (relative rate, 1.35; 95% CI, 1.15 to 1.58). Adjustment for other prognostic factors failed to substantially affect this observation. When initiated after the time of AIDS diagnosis, zidovudine was associated with improved prognosis but for no more than 2 years after starting therapy.

Rainer Werner Fassbinder's Garbage, the City and Death: Renewed Antagonisms in the Complex Relationship between Jews and Germans in the Federal Republic of Germany

On December 17, 1985 about 40people gathered at the Centerfor European Studies to hearpresentations on various aspects of the controversy surrounding the Fassbinderplay, Garbage, the City and Death, (Der Midll, die Stadt und der Tod). The event was sponsored by two of the Center's study groups: The Jews in Modem Europe Study Group and The German Study Group. The immediate contextfor this seminar was set by the incident and its aftermath in the late spring of 1985. Observers on both sides of the Atlantic were disturbed by the actions and statements of President Reagan and Chancellor Kohl and were disappointed by the concomitant lack of protest on the part of much of the West German Left. Two ofthe panel members in the CES roundtable contributed to this inter-continental debate. Moishe Postone's essay Bitburg und die Linke, published in Pflasterstrand onJune 1, 1985 and Andrei S. Markovits' letter Ein offener Brief an die deutsche Linke: Kliglich versagt appearing in die tageszeitung on May 9, 1985, both elicited lively and varied responses andfanned theflames ofcontroversy