Swedish Society of Medicine

A comprehensive translational cancer research approach focused on personalized and precision medicine, and covering the entire cancer research-care-prevention continuum has the potential to achieve in 2030 a 10-year cancer-specific survival for 75% of patients diagnosed in European Union (EU) member states with a well-developed healthcare system. Concerted actions across this continuum that spans from basic and preclinical research through clinical and prevention research to outcomes research, along with the establishment of interconnected high-quality infrastructures for translational research, clinical and prevention trials and outcomes research, will ensure that science-driven and social innovations benefit patients and individuals at risk across the EU. European infrastructures involving comprehensive cancer centres (CCCs) and CCC-like entities will provide researchers with access to the required critical mass of patients, biological materials and technological resources and can bridge research with healthcare systems. Here, we prioritize research areas to ensure a balanced research portfolio and provide recommendations for achieving key targets. Meeting these targets will require harmonization of EU and national priorities and policies, improved research coordination at the national, regional and EU level and increasingly efficient and flexible funding mechanisms. Long-term support by the EU and commitment of Member States to specialized schemes are also needed for the establishment and sustainability of trans-border infrastructures and networks. In addition to effectively engaging policymakers, all relevant stakeholders within the entire continuum should consensually inform policy through evidence-based advice.

To study the efficacy and safety of anti-CD52 antibody (alemtuzumab) in the treatment of refractory and relapsing Behçet disease (BD). Thirty-two patients (22 women) with BD received 60 courses of alemtuzumab between 1994 and 2013. Three-dose regimens were used: 134 mg in 21 courses (Group 1), 95 mg in 18 courses (Group 2), and 60 mg in 21 courses (Group 3). Immunosuppressive drugs were stopped at the time of alemtuzumab, and prednisolone was reduced according to clinical response. Treatment response was assessed by clinical status, inflammatory activity, prednisolone dose, and the need for subsequent immunosuppressive drugs and disease relapse. After the first alemtuzumab course, 27 of 32 patients (84%) achieved partial or complete remission (CR). Fifty of 60 courses (83%) resulted in remission (66% CR) without differences in remission rates between dosing regimens. Profound lymphocyte depletion occurred after all courses. Relapse-free survival rates were 83.6% at 6 months and 52.8% at 12 months, and were higher among Group 1 patients (Group 1: 100% and 77.8%, Group 2: 81.3% and 37.5%, and Group 3: 65.0% and 37.1%, p < 0.001). Mild to moderate infusion reactions occurred after 16 courses (27%). Eight patients (25%) developed symptomatic thyroid disease. Alemtuzumab led to remission in the majority of patients with difficult-to-treat BD. Relapse was common and may be associated with lower dosing. Adverse events included infusion reactions and new autoimmunity. Achieving complete lymphocyte depletion did not affect the remission rate or duration.

Diago et al.1 reported results for genotype 2/3–infected patients treated for at least 80% of the planned duration in the a randomized, open-label study of the effect of PEGASYS and ribavirin combination therapy on sustained virologic response in interferon-naïve patients with chronic hepatitis C genotype 2 or 3 infection (ACCELERATE) trial. Among patients achieving a rapid virological response [RVR; i.e., undetectable hepatitis C virus (HCV) RNA after 4 weeks of therapy according to an assay with a limit of detection of <50 IU/mL], sustained virological response (SVR) rates of 82% and 91% were observed for patients treated for 16 and 24 weeks, respectively. When this analysis was restricted to patients with a baseline viral load less than or equal to 400,000 IU/mL (25% of all patients), the SVR rates were 91% and 95%, respectively. We recently presented results from a trial of HCV genotype 2/3–infected patients (the NORDynamIC study; n = 382) who received peginterferon alfa-2a weekly plus 800 mg of ribavirin daily for 12 or 24 weeks. Serial HCV RNA samples were analyzed with reverse-transcription polymerase chain reaction with a limit of detection of <15 IU/mL.2 Three hundred three patients (79%) received at least 80% of the target doses of peginterferon alfa-2a and ribavirin for at least 80% of the target treatment duration, and they were thus included in a per protocol analysis. In comparison with 12 weeks of treatment, 24 weeks of treatment resulted in higher SVR rates in patients with undetectable HCV RNA (P < 0.0001, chi-square test and Fisher's exact test), in patients with HCV RNA levels of 15-50 IU/mL (P = 0.02, Fisher's exact test), and in patients with HCV RNA levels < 50 IU/mL on day 29 (P = 0.009, Fisher's exact test). When this analysis was restricted to patients with a baseline viral load less than or equal to 400,000 IU/mL (n = 73), as suggested by Diago et al.,1 35 of 37 patients (95%) in the 12-week study arm achieved SVR, whereas 36 of 36 patients (100%) in the 24-week arm achieved SVR. These results support the idea that short-term therapy is suitable for patients with low baseline viral loads who achieve RVR and do not require major dose reductions. However, the algorithm proposed by Diago et al.1 requires two HCV RNA analyses (at the baseline and in week 4). The results of the NORDynamIC trial imply that a single HCV RNA analysis with a cutoff level of 1000 IU/mL on day 7 predicts SVR as accurately as RVR and identifies at least as many candidates suitable for short-term therapy (28% versus 25% for the algorithm proposed by Diago et al.). Also, the suggested cutoff level of 1000 IU/mL is stably quantifiable by most currently available assays and is not prone to redefinition as the limits of detection of HCV RNA analyses further improve over time. Martin Lagging M.D.*, Åsa Alsiö M.D.*, Nina Langeland M.D. , Court Pedersen M.D. , Martti Färkkilä M.D.§, Mads Rauning Buhl M.D.¶, Kristine Mørch M.D. , Kristoffer Hellstrand M.D.*, Gunnar Norkrans M.D.*, * Department of Infectious Diseases, Gothenburg University, Gothenburg, Sweden, Department of Infectious Diseases, Haukeland University Hospital and Institute of Medicine, University of Bergen, Bergen, Norway, Department of Infectious Diseases, University of Southern Denmark, Odense, Denmark, § Department of Gastroenterology, Helsinki University, Helsinki, Finland, ¶ Department of Infectious Diseases, Aarhus University, Aarhus, Denmark.

The emphasis of the EFCS Congress held in Venice in October 2006 was on the future of Cytopathology in relation to events in Europe. Much of the discussion centred on the role of human papilloma virus testing and its impact on the provision of cervical screening. The following is a transcript of the discussion that took place at the Advisory Board Meeting for the journal Cytopathology, with some additional written comments received prior to the meeting. A brief summary has been provided as a conclusion by Dr A. Herbert.

The neuropeptide Y (NPY) signal peptide polymorphism T1128C has been linked to several risk factors for cardiovascular disease. The aim of the present study was to evaluate the significance of this polymorphism for cardiovascular and cerebrovascular disease outcome. In a prospective study cohort, 1032 hypertensive patients (174 myocardial infarction and 170 stroke patients and 688 matched controls) were analysed for the T1128C polymorphism in the NPY gene. The dynamic allele specific hybridization (DASH) method was used for genotyping. Serum from the same participants was analysed for total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides. The frequency of the NPY T1128C polymorphism was 8.4% among patients with a myocardial infarction or stroke, as compared to 5.1% in the control group (P = 0.040). The difference remained significant after adjustment for the cardiovascular risk factors age, sex, smoking status, body mass index, systolic and diastolic blood pressure, presence of diabetes, total cholesterol, HDL, LDL and triglycerides. The present study indicates that the NPY T1128C polymorphism is an independent predictor for myocardial infarction and stroke in a Swedish hypertensive population.

The purpose of the investigation was to assess the effects of desflurane (DES) on left ventricular heart function during basal barbiturate anesthesia in a closed-pericardium, closed-chest acute swine model. The study was performed in 11 normoventilated adult pigs. Hemodynamic measurements were obtained using arterial, central venous, and pulmonary artery catheters, as well as a conductance volumetry and tip manometry catheter placed in the left ventricle. Hemodynamic measurements were recorded during basal pentobarbital anesthesia and with the addition of 1%, 2%, 4%, and 6% DES. DES dose-dependently decreased mean arterial pressure, systemic vascular resistance, left ventricular end-systolic pressure, dP/dtMAX and dP/dtMIN. At doses >1%, decreases in CO, stroke volume, ejection fraction, end-systolic elastance, preload recruitable stroke work, preload adjusted maximal power, and peak filling rate were observed. Heart rate decreased at 4% and 6% DES. Isovolumetric relaxation time increased only at 6% DES. We conclude that smaller doses of DES have a significant cardiodepressive effect in the setting of barbiturate infusion, as measured by conductance volumetry. Desflurane, in very small doses, depressed cardiac function during pentobarbital anesthesia with ketamine and benzodiazepine premedication in swine, as assessed by conductance volumetry and left ventricular pressure and volume relationship analysis. These results suggest that desflurane, in combination with certain anesthetics, can be cardiodepressive even in very small doses.