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Volume 140, No. 2930

Published July 19, 2010

Review article: Biomedical intelligence

  1. W Krenger, GA Holländer (Author)

    The role of the thymus in allogeneic haematopoietic stem cell transplantation

    Allogeneic haematopoietic stem cell transplantation (HSCT) is used to treat an increasing number of congenital and acquired disorders of the haematopoietic system. Even though cytoreductive conditioning regimens vary in intensity, all clinically used protocols invariably cause side effects that compromise transiently or long-term the response of the natural and the adaptive immune systems. However, in the context of the reconstruction of immunity, the generation of naïve T cells constitutes a slow process, and requires a functionally competent thymus. Unfortunately, regular thymic function is frequently suppressed by transplant-related toxicities. Most notably, graft-versus-host disease (GVHD) causes a state of posttransplantation immune deficiency. Here we discuss preclinical allogeneic HSCT models and clinical observations that have contributed to a detailed understanding of the cellular and molecular mechanisms responsible for the thymic dysfunction caused by acute GVHD. An in-depth knowledge of the mechanisms that control regular thymopoiesis and, conversely, affect thymus function is expected to provide the factual basis for the design of innovative therapies to recover T-cell numbers and function following allogeneic HSCT.

  2. S Conus (Author)

    Cathepsins and their involvement in immune responses

    The immune system is composed of an enormous variety of cells and molecules that generate a collective and coordinated response on exposure to foreign antigens, called the immune response. Within the immune response, endo-lysosomal proteases play a key role. In this review we cover specific roles of cathepsins in innate and adaptive immunity, as well as their implication in the pathogenesis of several diseases.

  3. R Salem, F Sibellas, T Socrates, N Arenja, A Mebazaa, MB Yilmaz (Author)

    Novelties in the early management of acute heart failure syndromes

    The recent European Society of Cardiology (ESC) guidelines delineate the diagnosis and management of distinct categories of acute heart failure syndromes. However, physicians dealing with these patients may need guidance in choosing therapeutic alternatives as soon as the dyspneic patient arrives at the emergency department, until distinct categories of the ESC guidelines are identified. Hence, this manuscript summarizes practical recommendations for the very early management of patients with acute heart failure syndromes. The recommendations are based on a clinical classification system considering the initial systolic blood pressure and other symptoms. Early initiation of diagnostic and goal-directed treatment strategies are key factors in improving patient outcomes. Early and frequent reassessment is also imperative so that adjustments to the initial therapeutic approach can be made, as clinically indicated.

Original article

  1. R Bertoli, M Bissig, D Caronzolo, M Odorico, M Pons, E Bernasconi (Author)

    Assessment of potential drug-drug interactions at hospital discharge

    Objective: The evaluation of the prevalence of potential drug-drug interactions and assessment of their clinical relevance in patients’ discharge medication in the medical ward of a community teaching hospital. The relevant clinical information was reported to the treating physicians.

    Methods: 200 patients at discharge from a medical ward were included. Prescribed drugs were analysed for interactions using commercially available software (Pharmavista®). Clinical pharmacists and a physician assessed the clinical relevance of detected interactions, eliminated those which were not considered clinically relevant and formulated recommendations for those considered clinically relevant. A written recommendation was given to the physician to provide rapid feedback before discharge.

    Results: The median age of the 200 patients studied was 69 years. At discharge, patients took an average of 7 different drugs. 62.5% of patients had at least one potential drug-drug interaction. In total, 373 potential drug-drug interactions were identified: 223 (60%) of minor severity, 143 (38%) of moderate severity and 7 (2%) of major severity.

    Conclusions: A computerised drug-drug interaction program (detection) together with clinical pharmacological experience (interpretation/evaluation) can be useful for decreasing the number of potentially harmful drug combinations. This approach may lead to an improvement in the quality of prescription, reducing possible risks and thus contributing to patient safety.

  2. U Klopfstein, J Kamber, H Zimmermann (Author)

    “On the way to light the dark”: a retrospective inquiry into the registered cases of domestic violence towards women over a six year period with a semi-quantitative analysis of the corresponding forensic documentation

    Aims: Domestic violence victims are increasingly identified at emergency departments (ED). Studies report a prevalence of 6–30%; women are more frequently affected and to a more serious extent than men. Studies have shown that without screening domestic violence victims are often not recognised. The primary aim of the study is to collect data descriptive of domestic violence victims and to show whether medical documentation meets the requirements of forensic medicine.

    Methods: Retrospective analysis of medical records using the ED electronic patient database (Qualicare, Qualidoc Bern) at the ED of Bern University Hospital, Inselspital. Demographics, injuries, perpetrators and a semi-quantitative analysis of the medical records have been evaluated for each case.

    Results: From 1 January 2000 to 31 December 2005, 40 914 women were admitted to the ED. During this time 160 women were identified as victims of domestic violence and met the inclusion criteria for our study. The age ranged from 15–68 years. 63.6% of these women are married or live in a steady relationship. 46% of all victims of domestic violence were treated from Fridays to Sundays. In 70.2% blunt trauma was documented, the head was affected in 49%, 53% showed injuries of only one body area. In 10 cases, strangulation was suspected. 75% of the assaults could be classified as simple assault on the basis of Swiss criminal law. The perpetrator was the husband or partner in 73.4%. 141 cases were included for a semi-quantitative evaluation of the forensic medical documentation. The type of injuries was described in every case, the localisation in 96%, the shape in 26% and the dimensions of the lesions in 36%.

    Conclusions: The present retrospective assessment of medical reports over a 6-year period shows that domestic violence against female patients was documented in 0.4%. This figure is far below the proportions to be expected from recent data. If these data are to be believed the majority of female victims of domestic violence must have been overlooked at the ED. The implementation of screening for domestic violence seems to be crucial. The types of injury are chiefly the result of superficial, blunt violence, meaning of mild degree from the viewpoint of criminal law. The quality of the forensic documentation is poor and usually insufficient for criminal prosecution. Clinicians require training in the forensic aspects of medical records.

  3. D Genné, J Borovicka, A Cerny, C Chuard, V Dutoit, R Malinverni, B Müllhaupt, M Monnat, F Negro, C Oneta, JP Chave, JF Dufour, JJ Gonvers, MH Heim (Author)

    Treatment of hepatitis C in HCV mono-infected and in HIV-HCV co-infected patients: an open-labelled comparison study

    Background/aims: Treatment of chronic HCV infection has become a priority in HIV+ patients, given the faster progression to end-stage liver disease. The primary endpoint of this study was to evaluate and compare antiviral efficacy of Peginterferon alpha 2a plus ribavirin in HIV-HCV co-infected and HCV mono-infected patients, and to examine whether 6 months of therapy would have the same efficacy in HIV patients with favourable genotypes 2 and 3 as in mono-infected patients, to minimise HCV-therapy-related toxicities. Secondary endpoints were to evaluate predictors of sustained virological response (SVR) and frequency of side-effects.

    Methods: Patients with genotypes 1 and 4 were treated for 48 weeks with Pegasys® 180 µg/week plus Copegus® 1000–1200 mg/day according to body weight; patients with genotypes 2 and 3 for 24 weeks with Pegasys® 180 µg/week plus Copegus® 800 mg/day.

    Results: 132 patients were enrolled in the study: 85 HCV mono-infected (38: genotypes 1 and 4; 47: genotypes 2 and 3), 47 HIV-HCV co-infected patients (23: genotypes 1 and 4; 24: genotypes 2 and 3). In an intention-to-treat analysis, SVR for genotypes 1 and 4 was observed in 58% of HCV mono-infected and in 13% of HIV-HCV co-infected patients (P = 0.001). For genotypes 2 and 3, SVR was observed in 70% of HCV mono-infected and in 67% of HIV-HCV co-infected patients (P = 0.973). Undetectable HCV-RNA at week 4 had a positive predictive value for SVR for mono-infected patients with genotypes 1 and 4 of 0.78 (95% CI: 0.54–0.93) and of 0.81 (95% CI: 0.64–0.92) for genotypes 2 and 3. For co-infected patients with genotypes 2 and 3, the positive predictive value of SVR of undetectable HCV-RNA at week 4 was 0.76 (95%CI, 0.50–0.93). Study not completed by 22 patients (36%): genotypes 1 and 4 and by 12 patients (17%): genotypes 2 and 3.

    Conclusion: Genotypes 2 or 3 predict the likelihood of SVR in HCV mono-infected and in HIV-HCV co-infected patients. A 6-month treatment with Peginterferon alpha 2a plus ribavirin has the same efficacy in HIV-HCV co-infected patients with genotypes 2 and 3 as in mono-infected patients. HCV-RNA negativity at 4 weeks has a positive predictive value for SVR. Aggressive treatment of adverse effects to avoid dose reduction, consent withdrawal or drop-out is crucial to increase the rate of SVR, especially when duration of treatment is 48 weeks. Sixty-one percent of HIV-HCV co-infected patients with genotypes 1 and 4 did not complete the study against 4% with genotypes 2 and 3.

  4. E Jeannot, P Mahler, O Duperrex, P Chastonay (Author)

    Evolution of overweight and obesity among 5–6-year-old schoolchildren in Geneva

    Questions under study: In view of the alarming trend in childhood obesity (O) and overweight (OW) observed in certain countries, the aim of the study is to measure the prevalence of O and OW in successive cohorts of elementary school children in Geneva.

    Methods: All 5–6-year-old children attending public schools in the Canton of Geneva were measured and weighed during a systematic health check at school from 2003 to 2008. BMI was calculated and plotted on standardised BMI for age tables, using Cole’s and Kromeyer’s references.

    Results: Using Cole’s references, the overall trend was a small non-significant decrease for OW 0.7 points (p = 0.33) and O 0.5 points (p = 0.23) over the 5-year period. For girls, OW decreased by 1.1 point (p = 0.47) and O decreased by 0.5 points (p = 0.61), whilst for boys OW decreased by 0.3 points (p = 0.54) and O decreased by 0.6 points (p = 0.23). A non-significant decrease or stabilisation in the prevalence of overweight and obesity was observed over the 5-year period in both boys and girls.

    Conclusion: These observations corroborate observations from Sweden and France, showing a levelling off in obesity and overweight in young children.

  5. B Keller, LR Braathen, HP Marti, RE Hunger (Author)

    Skin cancers in renal transplant recipients: a description of the renal transplant cohort in Bern

    Background/aims: Skin tumours, in particular squamous-cell carcinomas (SCC), are the most common malignant conditions developing in transplant recipients. The aim of this study is to investigate the frequency and type of skin cancer in patients receiving immunosuppressive therapy after organ transplantation.

    Methods: Multivariate logistic regression analysis was performed on data of 243 renal transplant patients who attended the dermatology outpatient clinic for the first time after transplantation in the period January 2002–October 2005.

    Results: We found an increased risk of actinic keratosis (AK) and SCC in renal transplant recipients with a basal cell carcinoma (BCC) / SCC ratio of 1:7. Older patients had AK more frequently (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.06–1.15; p <0.0001) and SCC (OR 1.14, CI 1.07–1.22; p <0.0001) than younger patients. Men had AK (OR 0.19, CI 0.08–0.45; p = 0.0002) and SCC (OR 0.25, CI 0.07–0.89; p = 0.0332) more frequently than women. The duration of immunosuppressive therapy correlated significantly with the numbers of AKs (OR 1.15, CI 1.08–1.24; p <0.0001) and SCCs (OR 1.16, CI 1.05–1.28; p = 0.0025), and patients with fair skin had more AKs (OR 0.31, CI 0.14–1.24; p <0.0001) and SCCs (OR 0.11, CI 0.02–0.52; p = 0.0054) than darker skinned patients. We could not identify any specific immunosuppressive drug as a distinct risk factor for AK or non-melanoma skin cancer (NMSC).

    Conclusion: Skin cancers are increased in the renal transplant population. Main risk factors for skin cancers are fair skin type and long duration of immunosuppressive therapy. A follow-up programme is necessary for early detection of skin cancer and precancerous conditions. Preventive strategies should include specialist dermatological monitoring and self-examination.

  6. D Besse, M Bellavia, Ziegler de, D Wunder (Author)

    Fertility and cancer

    Principles: Women of reproductive age with cancer fear for their childbearing potential as a result of the cancer itself and chemo- and/or radiation-therapy.

    Methods: Starting in 2006, a dedicated task force was set up at Lausanne University Hospital (CHUV) to handle all cancer and fertility issues and, in certain cases, offer access to emergency assisted reproductive technologies (ART) to preserve further childbearing options. Help provided by the task force was offered within a multidisciplinary framework encompassing psychological counselling offered to each patient or couple.

    Results: We report here the salient points of the experience gained through dedicated psychological counselling offered to cancer patients concerned about their future fecundity. This was done with the intention of underscoring the most clinically relevant lessons learned through our experience at CHUV.

    Conclusions: The specific ‘cancer and fertility’ counselling instituted at CHUV offers support for young women or couples confronted with stressful cancer and fertility issues. This type of specific counselling, the resource counselling, appears to be a particularly appropriate tool for patients abruptly involved in difficult decision-making processes under time constraints and thus extremely vulnerable. The personal feedbacks from the patients also confirm the importance of offering specific counselling and timely psychological support of the type reported here to all women of reproductive age before starting chemo- and/or radiation-therapy.

Special article

  1. V Junod (Author)

    Retrospective research: what are the ethical and legal requirements?

    Retrospective research is conducted on already available data and/or biologic material. Whether such research requires that patients specifically consent to the use of “their” data continues to stir controversy. From a legal and ethical point of view, it depends on several factors. The main criteria to be considered are whether the data or the sample is anonymous, whether the researcher is the one who collected it and whether the patient was told of the possible research use. In Switzerland, several laws delineate the procedure to be followed. The definition of “anonymous” is open to some interpretation. In addition, it is debatable whether consent waivers that are legally admissible for data extend to research involving human biological samples. In a few years, a new Swiss federal law on human research could clarify the regulatory landscape. Meanwhile, hospital-internal guidelines may impose stricter conditions than required by federal or cantonal law. Conversely, Swiss and European ethical texts may suggest greater flexibility and call for a looser interpretation of existing laws. The present article provides an overview of the issues for physicians, scientists, ethics committee members and policy makers involved in retrospective research in Switzerland. It aims at provoking more open discussions of the regulatory problems and possible future legal and ethical solutions.