Journal of Internal Medicine

The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.

The First Key Symposium was held in Stockholm, Sweden, 2–5 September 2003. The aim of the symposium was to integrate clinical and epidemiological perspectives on the topic of Mild Cognitive Impairment (MCI). A multidisciplinary, international group of experts discussed the current status and future directions of MCI, with regard to clinical presentation, cognitive and functional assessment, and the role of neuroimaging, biomarkers and genetics. Agreement on new perspectives, as well as recommendations for management and future research were discussed by the international working group. The specific recommendations for the general MCI criteria include the following: (i) the person is neither normal nor demented; (ii) there is evidence of cognitive deterioration shown by either objectively measured decline over time and/or subjective report of decline by self and/or informant in conjunction with objective cognitive deficits; and (iii) activities of daily living are preserved and complex instrumental functions are either intact or minimally impaired.

Fraser JRE, Laurent TC, Laurent UBG (Monash University, Clayton, Victoria, Australia; and University of Uppsala, Uppsala, Sweden). Hyaluronan: its nature, distribution, functions and turnover (Minisymposium: Hyaluronan). J Intern Med 1997; 242: 27–33.

Hyaluronan is a polysaccharide found in all tissues and body fluids of vertebrates as well as in some bacteria. It is a linear polymer of exceptional molecular weight, especially abundant in loose connective tissue. Hyaluronan is synthesized in the cellular plasma membrane. It exists as a pool associated with the cell surface, another bound to other matrix components, and a largely mobile pool. A number of proteins, the hyaladherins, specifically recognize the hyaluronan structure. Interactions of this kind bind hyaluronan with proteoglycans to stabilize the structure of the matrix, and with cell surfaces to modify cell behaviour. Because of the striking physicochemical properties of hyaluronan solutions, various physiological functions have been assigned to it, including lubrication, water homeostasis, filtering effects and regulation of plasma protein distribution. In animals and man, the half‐life of hyaluronan in tissues ranges from less than 1 to several days. It is catabolized by receptor‐mediated endocytosis and lysosomal degradation either locally or after transport by lymph to lymph nodes which degrade much of it. The remainder enters the general circulation and is removed from blood, with a half‐life of 2–5 min, mainly by the endothelial cells of the liver sinuoids.

Physician burnout, a work‐related syndrome involving emotional exhaustion, depersonalization and a sense of reduced personal accomplishment, is prevalent internationally. Rates of burnout symptoms that have been associated with adverse effects on patients, the healthcare workforce, costs and physician health exceed 50% in studies of both physicians‐in‐training and practicing physicians. This problem represents a public health crisis with negative impacts on individual physicians, patients and healthcare organizations and systems. Drivers of this epidemic are largely rooted within healthcare organizations and systems and include excessive workloads, inefficient work processes, clerical burdens, work–home conflicts, lack of input or control for physicians with respect to issues affecting their work lives, organizational support structures and leadership culture. Individual physician‐level factors also play a role, with higher rates of burnout commonly reported in female and younger physicians. Effective solutions align with these drivers. For example, organizational efforts such as locally developed practice modifications and increased support for clinical work have demonstrated benefits in reducing burnout. Individually focused solutions such as mindfulness‐based stress reduction and small‐group programmes to promote community, connectedness and meaning have also been shown to be effective. Regardless of the specific approach taken, the problem of physician burnout is best addressed when viewed as a shared responsibility of both healthcare systems and individual physicians. Although our understanding of physician burnout has advanced considerably in recent years, many gaps in our knowledge remain. Longitudinal studies of burnout's effects and the impact of interventions on both burnout and its effects are needed, as are studies of effective solutions implemented in combination. For medicine to fulfil its mission for patients and for public health, all stakeholders in healthcare delivery must work together to develop and implement effective remedies for physician burnout.

Obesity is a risk factor for diabetes, cardiovascular disease events, cancer and overall mortality. Weight loss may protect against these conditions, but robust evidence for this has been lacking. The Swedish Obese Subjects (SOS) study is the first long‐term, prospective, controlled trial to provide information on the effects of bariatric surgery on the incidence of these objective endpoints. The SOS study involved 2010 obese subjects who underwent bariatric surgery [gastric bypass (13%), banding (19%) and vertical banded gastroplasty (68%)] and 2037 contemporaneously matched obese control subjects receiving usual care. The age of participants was 37–60 years and body mass index (BMI) was ≥34 kg m⁻² in men and ≥38 kg m⁻² in women. Here, we review the key SOS study results published between 2004 and 2012. Follow‐up periods varied from 10 to 20 years in different reports. The mean changes in body weight after 2, 10, 15 and 20 years were −23%, −17%, −16% and −18% in the surgery group and 0%, 1%, −1% and −1% in the control group respectively. Compared with usual care, bariatric surgery was associated with a long‐term reduction in overall mortality (primary endpoint) [adjusted hazard ratio (HR) = 0.71, 95% confidence interval (CI) 0.54–0.92; P = 0.01] and decreased incidences of diabetes (adjusted HR=0.17; P < 0.001), myocardial infarction (adjusted HR = 0.71; P = 0.02), stroke (adjusted HR=0.66; P = 0.008) and cancer (women: adjusted HR = 0.58; P = 0.0008; men: n.s.]. The diabetes remission rate was increased severalfold at 2 years [adjusted odds ratio (OR) = 8.42; P < 0.001] and 10 years (adjusted OR = 3.45; P < 0.001). Whereas high insulin and/or high glucose at baseline predicted favourable treatment effects, high baseline BMI did not, indicating that current selection criteria for bariatric surgery need to be revised.

The idiopathic inflammatory myopathies are characterized by muscle weakness, skin disease and internal organ involvement. Autoimmunity is known to have a role in myositis pathogenesis, and myositis‐specific autoantibodies, targeting important intracellular proteins, are regarded as key biomarkers aiding in the diagnosis of patients. In recent years, a number of novel myositis autoantibodies including anti‐TIF1, anti‐NXP2, anti‐MDA5, anti‐SAE, anti‐HMGCRand anti‐cN1A have been identified in both adult and juvenile patients. These autoantibodies correlate with distinct clinical manifestations and importantly are found in inclusion body, statin‐induced, clinically amyopathic and juvenile groups of myositis patients, previously believed to be mainly autoantibody negative. In this review, we will describe the main myositis‐specific and myositis‐associated autoantibodies and their frequencies and clinical associations across different ages and ethnic groups. We will also discuss preliminary studies investigating correlations between specific myositis autoantibody titres and clinical markers of disease course, collectively demonstrating the utility of myositis autoantibodies as both diagnostic and prognostic markers of disease.

Abstract. Microdialysis is a technique for sampling the chemistry of the individual tissues and organs of the body, and is applicable to both animal and human studies. The basic principle is to mimic the function of a capillary blood vessel by perfusing a thin dialysis tube implanted into the tissue with a physiological liquid. The perfusate is analysed chemically and reflects the composition of the extracellular fluid with time due to the diffusion of substances back and forth over the membrane. Microdialysis is thus a technique whereby substances may be both recovered from and supplied to a tissue. The most important features of microdialysis are as follows: it samples the extracellular fluid, which is the origin of all blood chemistry; it samples continuously for hours or days without withdrawing blood; and it purifies the sample and simplifies chemical analysis by excluding large molecules from the perfusate. However, the latter feature renders the technique unsuitable for sampling large molecules such as proteins. The technique has been extensively used in the neurosciences to monitor neurotransmitter release, and is now finding application in monitoring of the chemistry of peripheral tissues in both animal and human studies.

In a prospective study all positive phlebographies within the well‐defined population of the city of MalmÖ, Sweden, during 1987 were studied in order to determine the incidence of deep venous thrombosis (DVT). Epidemiological data were analysed for the detection of patient groups at increased risk of DVT. The incidence was found to be equal for both sexes, i.e. 1.6 per 1000 inhabitants and year. Risk factors were found to be in accordance with earlier studies. The median age for men was 66 years, compared to 72 years for women. At diagnosis of DVT, 19% of subjects had a known malignancy and within 1 year 5% (19 cases) developed a new malignancy. Of the men, 29% had postoperative or post‐traumatic (fracture) DVT, compared to 46% of the women. Fewer patients with DVT than expected (39%) belonged to blood group 0 (31%) (P < 0.005). Pulmonary embolism (PE) was clinically suspected in only 5% of cases, and diagnosis was verified scintigraphically in 2% of cases. None of these died of PE, but of 6 patients who were found to have PE at autopsy, four died about 4 weeks after the DVT was diagnosed.

Adiponectin is an adipocyte‐derived hormone that was discovered in 1995. Unlike leptin, which was identified around the same time, the clinical relevance of adiponectin remained obscure for a number of years. However, starting in 2001, several studies were published from different laboratories that highlighted the potential antidiabetic, antiatherosclerotic and anti‐inflammatory properties of this protein complex. Methods to measure the protein with high throughput assays in clinical samples were developed shortly thereafter, and as a result hundreds of clinical studies have been published over the past 3 years describing the role of adiponectin in endocrine and metabolic dysfunction. Furthermore, adiponectin research has expanded to include a role for adiponectin in cancer and other disease areas. Although it is an impossible task to summarize the findings from all these studies in a single review, we aim to demonstrate the utility of circulating adiponectin as a biomarker of the metabolic syndrome. Evidence for this relationship will include how decreased levels of plasma adiponectin (‘hypoadiponectinaemia’) are associated with increased body mass index (BMI), decreased insulin sensitivity, less favourable plasma lipid profiles, increased levels of inflammatory markers and increased risk for the development of cardiovascular disease. Therefore, adiponectin levels hold great promise for use in clinical application serving as a potent indicator of underlying metabolic complications.

Abstract. Kuper H, Adami H‐O & Trichopoulos D (Harvard School of Public Health, Boston, MA, USA; Karolinska Institute, Stockholm, Sweden; University of Athens Medical School, Greece). Infections as a major preventable cause of human cancer (Internal Medicine in the 21st Century). J Intern Med 2000; 248: 171–183.

Infections may be responsible for over 15% of all malignancies worldwide. Important mechanisms by which infectious agents may induce carcinogenesis include the production of chronic inflammation, the transformation of cells by insertion of oncogenes and inhibition of tumour suppressors, and the induction of immunosuppression. Common characteristics shared by infectious agents linked to malignancies are that they are persistent in the host, often highly prevalent in the host population and induce cancer after a long latency. The associations between a selection of infectious agents and malignancies are covered in detail.