Showing papers in "Swiss Medical Weekly in 2016"

Common invasive fungal diseases: an overview of invasive candidiasis, aspergillosis, cryptococcosis, and Pneumocystis pneumonia.

Abstract: Every year, Candida, Aspergillus, Cryptococcus and Pneumocystis infect an estimated two million individuals worldwide. Most are immunocompromised or critically ill. Candida is the most common fungal pathogen of the critically ill and of recipients of transplanted abdominal organs. In high-risk haemato-oncological patients, in contrast, the introduction of antifungal prophylaxis with fluconazole and later with mould-active posaconazole has led to a remarkable reduction of invasive candidiasis and is likely to have a similar effect on invasive aspergillosis. Invasive aspergillosis remains the dominant invasive fungal disease (IFD) of haemato-oncological patients and solid-organ transplant recipients and is increasingly found in individuals with exacerbated chronic obstructive pulmonary disease on corticosteroids. In the developed world, owing to antiretroviral therapy Pneumocystis pneumonia and cryptococcosis have become rare in patients with human immunodeficiency virus (HIV) and are mainly found in solid-organ transplant recipients or immunocompromised patients. In the developing world, cryptococcosis remains a common and highly lethal disease of HIV positive individuals. With invasive candidiasis and invasive aspergillosis, timely diagnosis is the principal challenge. The clinical presentation is nonspecific and current diagnostic tests lack sensitivity and specificity. The combination of several tests improves sensitivity, but not specificity. Standardised polymerase chain-reaction-based assays may be promising tools for more rapid and specific diagnosis of candidiasis and invasive aspergillosis. Nevertheless, initiation of treatment is often based solely on clinical suspicion. Empirical therapy, however, may lead to over-treatment of patients without IFD or it may miss its target in the case of resistance. Despite the success of antifungal prophylaxis in reducing the incidence of IFDs in haemato-oncological patients, there are a considerable number of breakthrough infections demonstrating not only fungal resistance but also the emergence of rare and often lethal fungal pathogens. Knowledge of the local epidemiology and antifungal resistance is therefore pivotal. Current trial-based guidelines leave major gaps in identifying those most at risk, who may benefit from prophylaxis. Ongoing searches for disease-associated genetic polymorphisms may contribute to the establishment of individual risk profiles and targeted prophylaxis.

Amyloid-β pathology and cerebral amyloid angiopathy are frequent in iatrogenic Creutzfeldt-Jakob disease after dural grafting

Abstract: QUESTIONS UNDER STUDY: Alzheimer-type amyloid-β (Aβ) pathology was reported in brains of individuals developing iatrogenic Creutzfeldt-Jakob disease (iCJD) after treatment with human cadaveric growth hormone, and interpreted as evidence of human transmission of Aβ by the treatment. Here we investigated the prevalence of Aβ pathology in other instances of iCJD related to dura mater grafts. METHODS: By use of immunohistochemistry for Aβ, we investigated seven brains of patients (age range 28–63) who succumbed to iCJD after dural grafting, which had been applied by means of neurosurgery between 11 and 25 years before death. For control, we examined a series of 21 brains of age-matched (40–63 years) patients with sporadic CJD (sCJD) and an additional series of 81 sCJD cases (55–85 years) with the same methods. RESULTS: In five of seven iCJD brains, Aβ was deposited in meningeal vessels as congophilic amyloid angiopathy and brain parenchymal plaques. This was significantly (p <0.001) more frequent than in the age-matched sCJD controls and in the usual sCJD series. CONCLUSIONS: We conclude that congophilic amyloid angiopathy and brain parenchymal Aβ plaques are frequent in iCJD after dural grafting. The presence of Aβ pathology in young individuals is highly unusual and suggests a causal relationship to the dural grafts. Further studies will be needed to elucidate whether such pathology resulted from the seeding of Aβ aggregates from the grafts to host tissues.

False positive dengue NS1 antigen test in a traveller with an acute Zika virus infection imported into Switzerland.

Abstract: We report the first case of an acute Zika virus infection imported into Switzerland by a traveller returning from Canoa Quebrada, Ceara state, in the north-eastern part of Brazil. Due to a false positive dengue virus NS1 antigen test, IgG antibody seroconversion and a suggestive clinical picture,an acute dengue fever was initially considered. However, because of lack of specific IgM-antibodies, stationary IgG antibody titre and a negative dengue virus PCR test result, a dengue virus infection was excluded and a cross-reaction with other, causative flaviviruses was postulated. Based on recent reports of Zika fever cases in the north-eastern parts of Brazil, an acute Zika virus infection was suspected. Because of a lack of commercially available Zika virus diagnostic tests, the case was confirmed in the WHO reference laboratory. As the clinical presentation of Zika virus infection can be confused with dengue fever and chikungunya fever, and because of possible public health implications, all patients returning from affected areas should be additionally tested for Zika virus. This case illustrates the urgent medical need for a broadly available assay capable of differentiating Zika from Dengue infections.

Types of abuse and risk factors associated with elder abuse.

Abstract: PRINCIPLES Detecting elder abuse is challenging because it is a taboo, and many cases remain unreported. This study aimed to identify types of elder abuse and to investigate its associated risk factors. METHODS Retrospective analyses of 903 dossiers created at an Independent Complaints Authority for Old Age in the Canton of Zurich, Switzerland, from January 1, 2008 to October 31, 2012. Characteristics of victims and perpetrators, types of abuse, and associated risk factors related to the victim or the perpetrator were assessed. Bi- and multivariate analysis were used to identify abuse and neglect determinants. RESULTS A total of 150 cases reflected at least one form of elder abuse or neglect; 104 cases were categorised as abuse with at least one type of abuse (overall 135 mentions), 46 cases were categorised as neglect (active or passive). Psychological abuse was the most reported form (47%), followed by financial (35%), physical (30%) and anticonstitutional abuse (18%). In 81% of the 150 cases at least two risk factors existed. In 13% no associated risk factor could be identified. Compared with neglect, elders with abuse were less likely to be a nursing home resident than living at home (odds ratio [OR] 0.02, 95% confidence interval [CI] 0.00-0.19). In addition, they were more likely to be cohabiting with their perpetrators (OR 18.01, 95% CI 4.43-73.19). CONCLUSION For the majority of the reported elder abuse cases at least two associated risk factors could be identified. Knowledge about these red flags and a multifaceted strategy are needed to identify and prevent elder abuse.

The "Profiles" document: a modern revision of the objectives of undergraduate medical studies in Switzerland.

Abstract: The Joint Commission of the Swiss Medical Schools (SMIFK/CIMS) decided in 2000 to establish a Swiss Catalogue of Learning Objectives (SCLO) for undergraduate medical training, which was adapted from a similar Dutch blueprint. A second version of the SCLO was developed and launched in 2008. The catalogue is a prerequisite for the accreditation of the curricula of the six Swiss medical faculties and defines the contents of the Federal Licensing Examination (FLE). Given the evolution of the field of medicine and of medical education, the SMIFK/CIMS has decided to embark on a total revision of the SCLO. This article presents the proposed structure and content of Profiles, a new document which, in the future, will direct the format of undergraduate studies and of the FLE. Profiles stands for the Principal Relevant Objectives for Integrative Learning and Education in Switzerland. It is currently being developed by a group of experts from the six Swiss faculties as well as representatives of other institutions involved in these developments. The foundations of Profiles are grounded in the evolution of medical practice and of public health and are based on up-to-date teaching concepts, such as EPAs (entrustable professional activities). An introduction will cover the concepts and a tutorial will be displayed. Three main chapters will provide a description of the seven 2015 CanMEDS roles, a list of core EPAs and a series of ≈250 situations embracing the most frequent and current conditions affecting health. As Profiles is still a work in progress, it is hoped that this paper will attract the interest of all individuals involved in the training of medical students.

Comorbidity in rheumatoid arthritis

Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory condition, which is associated with an increased risk of comorbidity from other diseases. RA disease severity is a major predictor of development of cardiovascular disease, serious infections and malignant lymphoma. This reflects the role of chronic inflammation in the underlying pathology. Recent surveys indicate that although clinical outcomes have improved in patients with RA, mainly owing to access to more efficient pharmacotherapy, comorbidity remains a major issue in many patients. Register-based observational studies are useful sources of information on the impact of comorbidity and the efficacy and safety of antirheumatic treatment in patients with coexisting diseases. As a part of strategies to improve further the management of patients with RA, multidisciplinary collaboration for prevention and early detection of comorbidities is of major importance.

Prolonged administration of β-lactam antibiotics - a comprehensive review and critical appraisal.

Abstract: Prolonged infusion of β-lactam antibiotics as either extended (over at least 2 hours) or continuous infusion is increasingly applied in intensive care units around the world in an attempt to optimise treatment with this most commonly used class of antibiotics, whose effectiveness is challenged by increasing resistance rates. The pharmacokinetics of β-lactam antibiotics in critically ill patients is profoundly altered secondary to an increased volume of distribution and the presence of altered renal function, including augmented renal clearance. This may lead to a significant decrease in plasma concentrations of β-lactam antibiotics. As a consequence, low pharmacokinetic/pharmacodynamic (PK/PD) target attainment, which is described as the percentage of time that the free drug concentration is maintained above the minimal inhibitory concentration (MIC) of the causative organism (fT>MIC), has been documented for β-lactam treatment in these patients when using standard intermittent bolus dosing, even for the most conservative target (50% fT>MIC). Prolonged infusion of β-lactams has consistently been shown to improve PK/PD target attainment, particularly in patients with severe infections. However, evidence regarding relevant patient outcomes is still limited. Whereas previous observational studies have suggested a clinical benefit of prolonged infusion, results from two recent randomised controlled trials of continuous infusion versus intermittent bolus administration of β-lactams are conflicting. In particular, the larger, double-blind placebo-controlled randomised controlled trial including 443 patients did not demonstrate any difference in clinical outcomes. We believe that a personalised approach is required to truly optimise β-lactam treatment in critically ill patients. This may include therapeutic drug monitoring with real-time adaptive feedback, rapid MIC determination and the use of antibiotic dosing software tools that incorporate patient parameters, dosing history, drug concentration and site of infection. Universal administration of β-lactam antibiotics as prolonged infusion, even if supported by therapeutic drug monitoring, is not yet ready for "prime time", as evidence for its clinical benefit is modest. There is a need for prospective randomised controlled trials that assess patient-centred outcomes (e.g. mortality) of a personalised approach in selected critically ill patients including prolonged infusion of β-lactams compared with the current standard of care.

Prevalence and characteristics of coronary artery anomalies detected by coronary computed tomography angiography in 5 634 consecutive patients in a single centre in Switzerland.

Abstract: STUDY PRINCIPLES Coronary computed tomography angiography (CCTA) allows three-dimensional visualisation of the origin, course and ending of the coronary vessels with high spatial resolution, yielding an accurate depiction of coronary artery anomalies (CAAs). This study sought to determine the prevalence, incidence and characteristics of CAAs detected with CCTA in a single centre in Switzerland. METHODS CAAs were retrospectively identified in 5 634 consecutive patients referred for CCTA between March 2007 and July 2015. Single coronary arteries, Bland-White-Garland syndrome, anomalous coronary arteries originating from the opposite site of the sinus of Valsalva (ACAOS) with an interarterial course and coronary artery fistulas were classified as potentially malignant CAAs. RESULTS We identified 145 patients with CAAs, resulting in an overall prevalence of 2.6% and cumulative incidence of 2.1% in all patients referred for CCTA in the observation period. Forty-nine (33.8%) patients showed malignant CAAs including 1 (0.7%) patient with Bland-White-Garland syndrome, 7 (4.8%) with single coronary arteries, 36 (24.8%) with ACAOS and an interarterial course, and 5 (3.5%) with coronary artery fistulas. The remaining 96 (66.2%) patients were classified as having benign variants. CONCLUSIONS The prevalence of CAA detected by CCTA is not negligible. Because of its noninvasive nature, relatively low cost and low radiation exposure, a further increase in the utilisation of CCTA may be expected, which may consequently be paralleled by an increasing absolute number of incidentally detected CAAs. Hence, awareness of the main issues and possible management strategies regarding CAAs is of importance for every treating physician.

The updated Swiss guidelines 2016 for the treatment and follow-up of cutaneous melanoma.

Abstract: Cutaneous melanoma is the most deadly cutaneous neoplasm. In order to guide treatment decisions and follow-up of melanoma patients, guidelines for the management of melanoma in Switzerland were inaugurated in 2001 and revised in 2006 and 2016. Recent data on surgical and medical treatments from randomised trials necessitated modification of the treatment and follow-up recommendations.

Excess mortality during the warm summer of 2015 in Switzerland.

Abstract: QUESTION UNDER STUDY In Switzerland, summer 2015 was the second warmest summer for 150 years (after summer 2003). For summer 2003, a 6.9% excess mortality was estimated for Switzerland, which corresponded to 975 extra deaths. The impact of the heat in summer 2015 in Switzerland has not so far been evaluated. METHODS Daily age group-, gender- and region-specific all-cause excess mortality during summer (June-August) 2015 was estimated, based on predictions derived from quasi-Poisson regression models fitted to the daily mortality data for the 10 previous years. Estimates of excess mortality were derived for 1 June to 31 August, at national and regional level, as well as by month and for specific heat episodes identified in summer 2015 by use of seven different definitions. RESULTS 804 excess deaths (5.4%, 95% confidence interval [CI] 3.0‒7.9%) were estimated for summer 2015 compared with previous summers, with the highest percentage obtained for July (11.6%, 95% CI 3.7‒19.4%). Seventy-seven percent of deaths occurred in people aged 75 years and older. Ticino (10.3%, 95% CI -1.8‒22.4%), Northwestern Switzerland (9.5%, 95% CI 2.7‒16.3%) and Espace Mittelland (8.9%, 95% CI 3.7‒14.1%) showed highest excess mortality during this three-month period, whereas fewer deaths than expected (-3.3%, 95% CI -9.2‒2.6%) were observed in Eastern Switzerland, the coldest region. The largest excess estimate of 23.7% was obtained during days when both maximum apparent and minimum night-time temperature reached extreme values (+32 and +20 °C, respectively), with 31.0% extra deaths for periods of three days or more. CONCLUSIONS Heat during summer 2015 was associated with an increase in mortality in the warmer regions of Switzerland and it mainly affected older people. Estimates for 2015 were only a little lower compared to those of summer 2003, indicating that mitigation measures to prevent heat-related mortality in Switzerland have not become noticeably effective in the last 10 years.

E-cigarette use in young Swiss men : is vaping an effective way of reducing or quitting smoking ?

Abstract: QUESTION UNDER STUDY: To test longitudinally differences in conventional cigarette use (cigarettes smoked, cessation, quit attempts) between vapers and nonvapers METHODS: Fifteen months follow-up of a sample of 5 128 20-year-old Swiss men The onset of conventional cigarette (CC) use among nonsmokers, and smoking cessation, quit attempts, changes in the number of CCs smoked among smokers at baseline were compared between vapers and nonvapers at follow-up, adjusted for nicotine dependence RESULTS: Among baseline nonsmokers, vapers were more likely to start smoking at follow-up than nonvapers (odds ratio [OR] 602, 95% confidence interval [CI] 281, 1288 for becoming occasional smokers, and OR = 1269, 95% CI 400, 4028 for becoming daily smokers) Vapers reported lower smoking cessation rates among occasional smokers at baseline (OR = 043 (019, 096); daily smokers: OR = 042 [015, 118]) Vapers compared with nonvapers were heavier CC users (6253 vs 1810 cigarettes per week, p <0001) and had higher nicotine dependence levels (216 vs 075, p <0001) at baseline The number of CCs smoked increased between baseline and follow-up among occasional smokers (b = 606, 95% CI 444, 768) and decreased among daily smokers (b = -503, 95% CI -869, -138), but there were no differential changes between vapers and nonvapers Vapers showed more quit attempts at follow-up compared with nonvapers for baseline occasional smokers (incidence rate ratio [IRR] 181, 95% CI 124, 264; daily smokers IRR 128, 95% CI 095, 173) CONCLUSIONS: We found no beneficial effects of vaping at follow-up for either smoking cessation or smoking reduction

Osteogenesis imperfecta: from diagnosis and multidisciplinary treatment to future perspectives

Abstract: Osteogenesis imperfecta is an inherited connective tissue disorder with wide phenotypic and molecular heterogeneity. A common issue associated with the molecular abnormality is a disturbance in bone matrix synthesis and homeostasis inducing bone fragility. In very early life, this can lead to multiple fractures and progressive bone deformities, including long bone bowing and scoliosis. Multidisciplinary management improves quality of life for patients with osteogenesis imperfecta. It consists of physical therapy, medical treatment and orthopaedic surgery as necessary. Medical treatment consists of bone-remodelling drug therapy. Bisphosphonates are widely used in the treatment of moderate to severe osteogenesis imperfecta, from infancy to adulthood. Other more recent drug therapies include teriparatide and denosumab. All these therapies target the symptoms and have effects on the mechanical properties of bone due to modification of bone remodelling, therefore influencing skeletal outcome and orthopaedic surgery. Innovative therapies, such as progenitor and mesenchymal stem cell transplantation, targeting the specific altered pathway rather than the symptoms, are in the process of development.

Late presentation to HIV care despite good access to health services: current epidemiological trends and how to do better.

Abstract: In 2014, there were 36.9 million people worldwide living with human immunodeficiency virus (PLWH), of whom 17.1 million did not know they were infected. Whilst the number of new human immunodeficiency virus (HIV) infections has declined globally since 2000, there are still regions where new infection rates are rising, and diagnosing HIV early in the course of infection remains a challenge. Late presentation to care in HIV refers to individuals newly presenting for HIV care with a CD4 count below 350 cells/µl or with an acquired immune deficiency syndrome (AIDS)-defining event. Late presentation is associated with increased patient morbidity and mortality, healthcare costs and risk of onward transmission by individuals unaware of their status. Further, late presentation limits the effectiveness of all subsequent steps in the cascade of HIV care. Recent figures from 34 countries in Europe show that late presentation occurs in 38.3% to 49.8% of patients newly presenting for care, depending on region. In Switzerland, data from patients enrolled in the Swiss HIV Cohort Study put the rate of late presentation at 49.8% and show that patients outside established HIV risk groups are most likely to be late presenters. Provider-initiated testing needs to be improved to reach these groups, which include heterosexual men and women and older patients. The aim of this review is to describe the scale and implications of late presentation using cohort data from Switzerland and elsewhere in Europe, and to highlight initiatives to improve early HIV diagnosis. The importance of recognising indicator conditions and the potential for missed opportunities for HIV testing is illustrated in three clinical case studies.

Implementation of a hospital-integrated general practice--a successful way to reduce the burden of inappropriate emergency-department use.

Abstract: PRINCIPLES Emergency departments (EDs) are overcrowded by lower acuity patients, which might be more efficiently treated by general practitioners (GPs). This study evaluated the impact of triaging lower acuity patients to a new hospital-integrated general practice (HGP) on ED case-load and the reasons for choosing the ED/HGP. METHODS AND RESULTS Patients were consecutively assessed according to the emergency severity index (ESI) to triage lower acuity patients to the HGP. Consultation numbers at the emergency centre (ED and HGP) increased by 43% between 2007 (n = 16 974) and 2011 (n = 24 331) (implementation of HGP in 2009). Although self-referrals increased significantly at the emergency centre from 54% to 63% (p <0.001), the proportion of self-referrals at the ED was significantly reduced to 48% (p = 0.007). The HGP was able to reduce the burden of increasing total consultations by 36%; 4.6% were referred back to the ED after triaging to the HGP. Overall, 95% of HGP patients were self-referred, Swiss nationals (65%) and with a personal GP (82%) they attended regularly (69%). The most common reason for presenting at the emergency centre was not being able to reach the GP (60%). Diagnoses were injury- (29%) and infection- (23%) related problems affecting the musculoskeletal (27%) system and skin (21%). CONCLUSION The HGP succeeded in reducing the burden of inappropriate ED use: the majority of low acuity self-referred patients were conclusively treated at the HGP. The HGP does not represent competition to the GP out-of-hours care service, since the main reason for presenting at the hospital was not lacking a relationship but the GPs' inaccessibility.

Prevention and therapy of leg ischaemia in extracorporeal life support and extracorporeal membrane oxygenation with peripheral cannulation.

Abstract: Extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) have been around for a long time, but it is only in recent years, with the advent of acute respiratory distress syndrome consecutive to influenza A (H1N1) infection, that these life-saving technologies have seen a broader application. Although the results of ECLS and ECMO are perceived as generally encouraging, there are still disturbing complications related to peripheral cannulation in general and, more specifically, to cannulation in the groin. The present review was designed to assess the magnitude of this latter problem, i.e. leg ischaemia related to ECLS and ECMO, in the literature and to identify strategies for possible therapies and, more importantly, prevention. The search strategy selected identified seven original articles with more than twenty patients, totalling 407 patients who underwent veno-arterial ECMO, and one large review dealing with all kinds of complications. For the original reports, the number of cases with veno-arterial support ranged from 21 to 143, with, as far as available, frequency of ischaemic complications between 11% and 52%, a reported range of surgical intervention between 9% and 22%, and a leg amputation rate from 2% to 10%. It appears that the number of reports dealing with lower extremity ischaemia during ECMO increases in parallel with the number of reports about ECMO. Strategies for early detection of peripheral ischaemia, interventions for efficient reperfusion, and measures for prevention including new concepts with smaller and eventually bidirectional arterial cannulas are discussed.

Direct oral anticoagulants in the elderly: systematic review and meta-analysis of evidence, current and future directions.

Abstract: Background Concerns regarding the use of direct oral anticoagulants (DOACs: apixaban, dabigatran, edoxaban, rivaroxaban) in the elderly persist owing to the lack of randomised controlled trials targeting this age group. Objectives The aim of this study was to assess the efficacy and safety of DOACs in elderly patients (aged 75 years or more) with atrial fibrillation or venous thromboembolism (VTE), based on already published large randomised trials. Methods EMBASE, MEDLINE and the Cochrane Library were searched from inception to June 2015 for phase III trials. Pooled odds ratios with 95% confidence intervals were calculated for the target population using the fixed effect model. Heterogeneity between trials was assessed using the I2 Higgins test. Results A total of 30 655 participants aged 75 or older from eight studies (two apixaban, one dabigatran, two edoxaban, three rivaroxaban) were included in the statistical evaluation. Pooled analysis revealed that treatment with a DOAC was associated with a statistically significant odds reduction for stroke and embolism in elderly patients with atrial fibrillation. Also, DOACs significantly reduced the number of recurrent VTE events or VTE-related deaths in the participants aged 75 years or more with VTE. There was no statistically significant difference in safety outcome for both indications with DOAC compared with vitamin K antagonists although some differences in safety profiles between the DOACs were apparent. Conclusion DOACs show the same or greater efficacy than vitamin K antagonists in elderly patients with atrial fibrillation and VTE. Individual differences between DOACs in terms of safety profile cannot be excluded on the basis of current evidence. Direct head-to-head comparisons are needed to investigate possible divergence in pharmacological profiles between DOACs. Additionally, further studies conducted in real-word settings and in the frail elderly are ongoing and it would be interesting to target this particular patient group.

Update of the Swiss guidelines on post-treatment Lyme disease syndrome.

Abstract: Lyme borreliosis is caused by Borrelia burgdorferi sensu lato infection, which responds well to antibiotic therapy in the overwhelming majority of cases. However, despite adequate antibiotic treatment some patients report persisting symptoms which are commonly summarised as post-treatment Lyme disease syndrome (PTLDS). In 2005, the Swiss Society of Infectious Diseases published a case definition for PTLDS. We aimed to review the scientific literature with a special emphasis on the last 10 years, questioning whether the definitions from 2005 are still valid in the light of current knowledge. Furthermore, we describe the clinical history of infection with Borrelia burgdorferi sensu lato, the estimated prevalence of PTLDS, the possible pathogenesis of PTLDS, and treatment options with an emphasis on clinical studies. In summary, we were unable to find a scientific reason for modification of the PTLDS definitions published in 2005. Thus, the diagnostic criteria remain unchanged, namely documented clinical and laboratory evidence of previous infection with B. burgdorferi, a completed course of appropriate antibiotic therapy, symptoms including fatigue, arthralgia, myalgia, cognitive dysfunction or radicular pain persisting for >6 months, a plausible timely association between documented B. burgdorferi infection and onset of symptoms (i.e., persistent or recurrent symptoms that began within 6 months of completion of a recommended antibiotic therapy for early or late Lyme borreliosis), and exclusion of other somatic or psychiatric causes of symptoms. The main therapeutic options remain cognitive behavioural therapy and low-impact aerobic exercise programmes. Growing and unequivocal evidence confirms that prolonged or repeated antibiotic therapy for PTLDS is not beneficial, but potentially harmful and therefore contraindicated. The Guidelines of the Swiss Society of Infectious Diseases offer an evidence based, diagnostic and therapeutic framework for physicians caring for patients suffering from presumptive PTLDS in Switzerland.

Complement receptor immunoglobulin: a control point in infection and immunity, inflammation and cancer

Abstract: The B7 family-related protein, V-set and Ig domain (VSIG4) / Z39Ig / complement receptor immunoglobulin (CRIg), is a new player in the regulation of immunity to infection and inflammation. The unique features of this receptor as compared with classical complement receptors, CR3 and CR4, have heralded the emergence of new concepts in the regulation of innate and adaptive immunity. Its selective expression in tissue macrophages and dendritic cells has been considered of importance in host defence and in maintaining tolerance against self-antigens. Although a major receptor for phagocytosis of complement opsonised bacteria, its array of emerging functions which incorporates the immune suppressive and anti-inflammatory action of the receptor have now been realised. Accumulating evidence from mouse experimental models indicates a potential role for CRIg in protection against bacterial infection and inflammatory diseases, such as rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus, and also in promotion of tumour growth. CRIg expression can be considered as a control point in these diseases, through which inflammatory mediators, including cytokines, act. The ability of CRIg to suppress cytotoxic T cell proliferation and function may underlie its promotion of cancer growth. Thus, the unique properties of this receptor open up new avenues for understanding of the pathways that regulate inflammation during infection, autoimmunity and cancer with the potential for new drug targets to be identified. While some complement receptors may be differently expressed in mice and humans, as well as displaying different properties, mouse CRIg has a structure and function similar to the human receptor, suggesting that extrapolation to human diseases is appropriate. Furthermore, there is emerging evidence in human conditions that CRIg may be a valuable biomarker in infection and immunity, inflammatory conditions and cancer prognosis.

Prospective validation and adaptation of the HOSPITAL score to predict high risk of unplanned readmission of medical patients.

Abstract: PRINCIPLES The HOSPITAL score is a simple prediction model that accurately identifies patients at high risk of readmission and showed good performance in an international multicentre retrospective study. We aimed to demonstrate prospectively its accuracy to predict 30-day unplanned readmission and death. METHODS We prospectively screened all consecutive patients aged ≥50 years admitted to the department of general internal medicine of a large community hospital in Switzerland. We excluded patients who refused to give consent, who died during hospitalisation, or who were transferred to another acute care, rehabilitation or palliative care facility. The primary outcome was the first unplanned readmission or death within 30 days after discharge. Some of the predictors of the original score (discharge from an oncology service and length of stay) were adapted according to the setting for practical reasons, before the start of patient inclusion. We also assessed a simplified version of the score, without the variable "any procedure performed during hospitalisation". The performance of the score was evaluated according to its overall accuracy (Brier score), its discriminatory power (C-statistic), and its calibration (Hosmer-Lemeshow goodness-of-fit test). RESULTS Among the 346 included patients, 40 (11.6%) had a 30-day unplanned readmission or death. The HOSPITAL score showed very good accuracy (Brier score 0.10), good discriminatory power (C-statistic 0.70, 95% confidence interval [CI] 0.62-0.79), and an excellent calibration (p = 0.77). Patients were classified into three risk categories for the primary outcome: low (59%), intermediate (20.8%) and high risk (20.2%). The estimated risks of unplanned readmission/death for each category were 8.2%, 11.3% and 21.6%, respectively. The simplified score showed the same performance, with a Brier score of 0.10, a C-statistic of 0.70 (95% CI 0.61-0.79), and a goodness-of-fit statistic of 0.40. CONCLUSIONS The HOSPITAL score prospectively identified patients at high risk of 30-day unplanned readmission or death with good performance in medical patients in Switzerland. Its simplicity and good performance make it an easy-to-use tool to target patients who might most benefit from intensive transitional care interventions.

Neutrophil extracellular traps in health and disease.

Abstract: Polymorphonuclear neutrophil granulocytes are the first responders of the immune system to threats by invading microorganisms. In the traditional view, they combat the intruders by phagocytosis and externalisation of granules containing lytic and microbicidal factors. A dozen years ago, this concept was expanded by the observation that neutrophils may react to bacteria by extruding their nuclear chromosomal DNA with attached nuclear and cytoplasmic constituents to form extracellular reticular structures. Since they trapped and immobilised the microbes, they were designated neutrophil extracellular traps (NETs), and their ensuing cell death NETosis. Subsequently, the NETs were shown to act against different types of pathogens, including viruses, and an intricate interplay between the NETs and countermeasures of the pathogens became apparent. The NETs were also found to induce inflammatory responses in the host that contributed to the pathophysiology of autoinflammatory and even autoimmune diseases. Of special interest is the direct link that NETs provide to infections that may initiate and maintain inflammation without the participation of adaptive immunity. In contrast, neutrophils seem capable of activating B cells to produce antibodies relevant to autoimmunity independently of T cell help. Further results imply NETs in the occurrence of thrombosis of the veins and recently also in the generation of arterial plaque. Data from the studies on the defence against pathogens and the pathophysiology of inflammation and thrombosis have started to drive applications to modulate NET formation and its effects and may provide opportunities to optimise current diagnostic and therapeutic concepts.

Metabolic syndrome and hypogonadism - two peas in a pod

Abstract: Testosterone deficiency is highly prevalent in up to 50% of men with the metabolic syndrome and type 2 diabetes mellitus. Low testosterone levels in men appear to be an independent cardiovascular risk factor and predictor of subsequent development of the metabolic syndrome. Reciprocally, the metabolic syndrome leads to a decrease in testosterone levels. This review provides an account of the pathophysiological mechanisms in the bidirectional relationship between hypogonadism and body composition, inflammation and insulin sensitivity as well as the effects of testosterone replacement on diverse metabolic parameters.

The role of low acid load in vegetarian diet on bone health: a narrative review.

Abstract: Vegetarian and vegan diets contain low amounts of protein and calcium. For this reason they are supposed to cause low bone mineral density (BMD) and osteoporosis. But this is not the case, except for vegans with a particularly low calcium intake. The absence of osteoporosis or low BMD can be explained by the low acid load of these diets. Nutritional acid load is negatively correlated with bone mineral density (BMD) and positively with fracture risk. Low acid load is correlated with lower bone resorption and higher BMD. It is linked to high intake of potassium-rich nutrients, such as fruits and vegetables, as found in vegetarian diets. The total nutritional acid load, which not only depends on the potassium content of the nutrition, was recently assessed in several studies on vegetarian and vegan diets and was found to be very low or absent, while the diet of Western-style omnivores produces daily 50 to 70 mEq of acid. This might be an important factor for the protection of vegetarians from osteoporosis.

HIV is not transmitted under fully suppressive therapy: The Swiss Statement - eight years later

Abstract: Eight years ago, on January 30th 2008, the Swiss Federal Commission for AIDS-related Issues (“the Commission”, now the Swiss Federal Commission for Sexual Health) published a statement which – in the field of human immunodeficiency virus (HIV) – rapidly received the name “The Swiss statement” [1]. The statement addressed the infectiousness of an HIV-positive person once the virus was stably suppressed for at least 6 months with antiretroviral therapy (ART). Despite the lack of results from large randomised studies, the Commission felt, based on an expert evaluation of HIV transmission risk under therapy, that the risk of HIV transmission in such a situation was negligible. The publication was primarily aimed at Swiss physicians, informing them that it was about time to discuss new data on infectiousness with patients. Problematic differences in prevention messages were already being observed by the Commission: some physicians openly discussed the very low risk of transmission on ART and reassured patients who said they had condomless sex with their steady partner, whereas others told HIV-positive patients under therapy that all condomless sex – even with their HIV-positive partner – was risky. At the time it was clear that ART did, in fact, reduce the likelihood of transmission, but the Commission’s estimate on the magnitude of this risk was neither discussed with patients nor communicated widely. The Commission summarised the epidemiological and biological knowledge known at the time and concluded that the risk of transmission in a differing HIV status partnership where the positive partner was on fully suppressive ART can be considered negligible. The focus of the paper was on how to communicate this information with an affected partnership where one partner was HIV positive.

Somatisation and anger are associated with symptom severity of posttraumatic stress disorder in severely traumatised refugees and asylum seekers.

Abstract: Background Most research on refugee mental health has focused on posttraumatic stress disorder (PTSD). Besides PTSD, however, traumatised refugees are often burdened by comorbid somatic and psychiatric conditions, as well as postmigration living difficulties (PMLD). It is unclear how these conditions interfere with presentation and treatment of PTSD. Methods This preliminary cross-sectional study investigated 134 severely traumatised refugees and asylum seekers in treatment in two psychiatric outpatient units in Switzerland. Trauma exposure, PMLD, somatisation and explosive anger were assessed and related to symptom severity of PTSD using correlation and regression analyses. Results PTSD symptoms were significantly related to somatisation, anger, PMLD and trauma exposure. Regression analysis revealed that PTSD symptoms were mainly predicted by somatisation and anger. Conclusions Symptom severity of PTSD is associated with somatisation, explosive anger and, to a lesser extent, PMLD. Standard PTSD treatment may benefit from implementing targeted strategies to assess and address these factors in traumatised refugees.

Microsurgery robots: addressing the needs of high-precision surgical interventions.

Abstract: Robotics has a significant potential to enhance the overall capacity and efficiency of healthcare systems. Robots can help surgeons perform better quality operations, leading to reductions in the hospitalisation time of patients and in the impact of surgery on their postoperative quality of life. In particular, robotics can have a significant impact on microsurgery, which presents stringent requirements for superhuman precision and control of the surgical tools. Microsurgery is, in fact, expected to gain importance in a growing range of surgical specialties as novel technologies progressively enable the detection, diagnosis and treatment of diseases at earlier stages. Within such scenarios, robotic microsurgery emerges as one of the key components of future surgical interventions, and will be a vital technology for addressing major surgical challenges. Nonetheless, several issues have yet to be overcome in terms of mechatronics, perception and surgeon-robot interfaces before microsurgical robots can achieve their full potential in operating rooms. Research in this direction is progressing quickly and microsurgery robot prototypes are gradually demonstrating significant clinical benefits in challenging applications such as reconstructive plastic surgery, ophthalmology, otology and laryngology. These are reassuring results offering confidence in a brighter future for high-precision surgical interventions.

Staphylococcus aureus and methicillin resistance in Switzerland: regional differences and trends from 2004 to 2014.

Abstract: BACKGROUND The global epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) is heterogeneous. The objective of this study was to evaluate MRSA epidemiology in Switzerland over an 11-year period. METHODS We conducted a retrospective study with time series analysis on S. aureus including MRSA and non-multidrug resistant MRSA (NmMRSA). We used NmMRSA as a marker for community-acquired MRSA. NmMRSA was defined as MRSA susceptible to at least three of the following agents: ciprofloxacin, clindamycin, tetracycline and trimethoprim-sulfamethoxazole. RESULTS A total of 14 648 MRSA and 115 917 methicillin-susceptible S. aureus (MSSA) isolates were included. Despite an overall decrease of the proportion of MRSA among S. aureus clinical isolates (from 14% in 2004 to 8% in 2014), an increasing trend in NmMRSA was observed. Variations in geographical distribution were noted, with a decrease in the proportion of MRSA in the Italian- and French-speaking regions (from 20-26% in 2004 to 12% in 2014) and low prevalence (3-5%) in the German-speaking region. We noticed an increase in the proportion of MRSA in outpatients (+0.03% per quarter per year) and in the younger population (+0.05% per quarter per year) compared with a decreasing trend in inpatients and the elderly. CONCLUSION The proportion of MRSA among S. aureus isolates in Switzerland decreased overall from 2004 to 2014. Worrisome increases of NmMRSA were found in younger persons and outpatients.

When membranes need an ESCRT: endosomal sorting and membrane remodelling in health and disease.

Abstract: Originally discovered as regulators of cargo sorting during endosomal trafficking, ESCRT (endosomal sorting complexes required for transport) proteins are emerging as flexible machines that shape the behaviour of membranes throughout the cell. Deregulation of ESCRT activity is observed in neuro-degenerative diseases, virus infection and cancer. However, the mechanisms of pathogenesis involving ESCRTs have not yet fully come into focus. Here, we review the current knowledge of ESCRT function in health and disease and provide educated guesses for future research and focused therapeutic intervention.

Mechanisms of protein homeostasis in health, aging and disease.

Abstract: When emerging from the ribosomes, new polypeptides need to fold properly, eventually translocate, and then assemble into stable, yet functionally flexible complexes. During their lifetime, native proteins are often exposed to stresses that can partially unfold and convert them into stably misfolded and aggregated species, which can in turn cause cellular damage and propagate to other cells. In animal cells, especially in aged neurons, toxic aggregates may accumulate, induce cell death and lead to tissue degeneration via different mechanisms, such as apoptosis as in Parkinson's and Alzheimer's diseases and aging in general. The main cellular mechanisms effectively controlling protein homeostasis in youth and healthy adulthood are: (1) the molecular chaperones, acting as aggregate unfolding and refolding enzymes, (2) the chaperone-gated proteases, acting as aggregate unfolding and degrading enzymes, (3) the aggresomes, acting as aggregate compacting machineries, and (4) the autophagosomes, acting as aggregate degrading organelles. For unclear reasons, these cellular defences become gradually incapacitated with age, leading to the onset of degenerative diseases. Understanding these mechanisms and the reasons for their incapacitation in late adulthood is key to the design of new therapies against the progression of aging, degenerative diseases and cancers.

Advanced ECG in 2016: is there more than just a tracing?

Abstract: The 12-lead electrocardiogram (ECG) is the most frequently used technology in clinical cardiology. It is critical for evidence-based management of patients with most cardiovascular conditions, including patients with acute myocardial infarction, suspected chronic cardiac ischaemia, cardiac arrhythmias, heart failure and implantable cardiac devices. In contrast to many other techniques in cardiology, the ECG is simple, small, mobile, universally available and cheap, and therefore particularly attractive. Standard ECG interpretation mainly relies on direct visual assessment. The progress in biomedical computing and signal processing, and the available computational power offer fascinating new options for ECG analysis relevant to all fields of cardiology. Several digital ECG markers and advanced ECG technologies have shown promise in preliminary studies. This article reviews promising novel surface ECG technologies in three different fields. (1) For the detection of myocardial ischaemia and infarction, QRS morphology feature analysis, the analysis of high frequency QRS components (HF-QRS) and methods using vectorcardiography as well as ECG imaging are discussed. (2) For the identification and management of patients with cardiac arrhythmias, methods of advanced P-wave analysis are discussed and the concept of ECG imaging for noninvasive localisation of cardiac arrhythmias is presented. (3) For risk stratification of sudden cardiac death and the selection of patients for medical device therapy, several novel markers including an automated QRS-score for scar quantification, the QRS-T angle or the T-wave peak-to-end-interval are discussed. Despite the existing preliminary data, none of the advanced ECG markers and technologies has yet accomplished the transition into clinical practice. Further refinement of these technologies and broader validation in large unselected patient cohorts are the critical next step needed to facilitate translation of advanced ECG technologies into clinical cardiology.

Nonmelanoma skin cancer in mountain guides: high prevalence and lack of awareness warrant development of evidence-based prevention tools.

Abstract: Aims of the study Nonmelanoma skin cancer (NMSC) is the most common cancer in Switzerland and Europe. The main causative factor is exposure to ultraviolet radiation, which puts outdoor workers in general at a higher risk of developing NMSC than indoor workers. However, few studies have clinically examined the risk of developing NMSC to outdoor workers, especially mountain guides. We aimed to investigate the prevalence of NMSC and corresponding precancerous lesions, and the associated risk behaviour of mountain and ski guides in order to develop future prevention programmes. Methods We conducted a cross-sectional study including mountain and ski guides from southern Germany, who underwent a full-body skin check-up by a dermatologist. We assessed their NMSC awareness and risk behaviour using a paper-based questionnaire. Results Of the 62 state-certified mountain and ski guides (55 men, 7 women; mean age 52.9 ± 13.4 years) included in this study, 27 (43.5%) were diagnosed with NMSC or its premalignant stages. In addition, 59.7% of the participants expressed the opinion that their protection from ultraviolet radiation exposure needs to be improved; 83.6% requested further information on NMSC, and 48.5% had never undergone a skin check-up or consulted a dermatologist before. Conclusions Mountain and ski guides are at a high risk for developing NMSC. Their unmet medical needs indicate an underestimation of NMSC prevalence, which is usually based on reports by insurance companies, and offer the chance for developing evidence-based awareness and prevention tools that can be promoted to individuals with other outdoor jobs.