Barbara Sperner-Unterweger

Systematic review reveals lack of quality in reporting health-related quality of life in patients with gastroenteropancreatic neuroendocrine tumours.

BackgroundGastroenteropancreatic neuroendocrine tumours (GEP-NET) are often slow-growing and patients may live for years with metastasised disease. Hence, along with increasing overall and progression-free survival, treatments aim at preserving patients’ well-being and health-related quality of life (HRQoL). However, studies on systematic HRQoL assessment in patients with GEP-NET are scarce. Therefore, the purpose of the current review is to systematically evaluate the methodological quality of the identified studies.MethodsA targeted database search was performed in PubMed, EMBASE, and CENTRAL. Data extraction was conducted by two independent researchers according to predefined criteria. For study evaluation, the Minimum Standard Checklist for Evaluating HRQoL Outcomes in Cancer Clinical Trials and the CONSORT Patient-Reported Outcome extension were adapted.ResultsThe database search yielded 48 eligible studies. We found the awareness for the need of HRQoL measurement to be growing and application of cancer-specific instruments gaining acceptance. Overall, studies were too heterogeneous in terms of patient characteristics and treatment interventions to draw clear conclusions for clinical practice. More importantly, a range of methodological shortcomings has been identified which were mainly related to the assessment and statistical analysis, as well as the reporting and interpretation of HRQoL data.ConclusionDespite an increasing interest in HRQoL in GEP-NET patients, there is still a lack of knowledge on this issue. A transfer of HRQoL results into clinical practice is hindered not only by the scarceness of studies, but also by the often limited quality of HRQoL processing and reporting.

Influence of mental stress on platelet bioactivity

It is well established that various mental stress conditions contribute, or at least influence, underlying pathophysiological mechanisms in somatic, as well as in psychiatric disorders; blood platelets are supposed to represent a possible link in this respect. The anculeated platelets are the smallest corpuscular elements circulating in the human blood. They display different serotonergic markers which seem to reflect the central nervous serotonin metabolism. They are known as main effectors in haematological processes but recent research highlights their role in the innate and adaptive immune system. Platelets are containing a multitude of pro-inflammatory and immune-modulatory bioactive compounds in their granules and are expressing immune-competent surface markers. Research gives hint that platelets activation and reactivity is increased by mental stress. This leads to enhanced cross talk with the immune system via paracrine secretion, receptor interaction and formation of platelet leucocyte-aggregates. Recently it has been demonstrated that the immune system can have a remarkable impact in the development of psychiatric disorders. Therefore platelets represent an interesting research area in psychiatry and their role as a possible biomarker has been investigated. We review the influence of mental stress on what is termed platelet bioactivity in this article, which subsumes the mainly immune-modulatory activity of platelets in healthy volunteers, elderly persons with chronic care-giving strain, patients with cardiovascular diseases who are prone to psychosocial stress, as well as in patients with posttraumatic stress disorder. Research data suggest that stress enhances platelet activity, reactivity and immune-modulatory capacities.

Mechanisms of Inflammation-Associated Depression: Immune Influences on Tryptophan and Phenylalanine Metabolisms

Metabolic parameters have a direct role in the regulation of immune cell function. Thereby the inflammation-induced metabolism of aromatic amino acids, most importantly of tryptophan and phenylalanine, plays a central role. In addition, neuropsychiatric conditions that go along with disorders that are characterized by acute or chronic inflammation, such as the development of depression, decreased quality of life or cognitive impairments, are connected to disturbed amino acid and subsequent neurotransmitter metabolism.The bioanalytical procedures for the determination of concentrations of tryptophan and phenylalanine and their respective first stable intermediates kynurenine and tyrosine as well as some analytical finesses and potential sources of errors are discussed in this chapter. Monitoring of these immunometabolic parameters throughout therapies in addition to biomarkers of immune response and inflammation such as neopterin can be useful to determine disease progression but also to plan psychiatric interventions timely, thus to establish personalized treatments.

Bioprofiling of platelets in medicated patients with depression

BACKGROUND Changes in platelet bioactivity and aggregation are of interest when studying patients with depression as this could help to explain the statistically observed association of depression and chronic somatic, especially cardiovascular disease. This link could potentially be mediated through serotonergic signaling or immunological changes. METHODS 38 medicated patients with major depressive disorder (MDD) and 30 mentally healthy controls, both without a diagnosis of cardiovascular disease, were included in this naturalistic study. Demographic and psychometric data were obtained. Platelet aggregability was measured by PFA-100 and bioactive compounds and serotonin levels were quantified in platelet sonicate. RESULTS The comparison of patients with controls revealed no changes in platelet aggregability, but significant differences in platelet content of several bioactive compounds. In a second analysis, patients were grouped according to the receptors and transporters influenced by their medication and again compared to controls. A significant effect of MDD was found for platelet content of serotonin, CD40L, interleukin-1β, and platelet factor-4, independent of medication. These markers can thus be classified as sensitive to MDD. The effect of medication on platelet parameters was also evaluated. Platelet content of matrix metalloproteinase-2 and β-thromboglobulin was normalized in MDD patients by medication acting on the serotonin transporter. LIMITATIONS Owing to the naturalistic study design, patients were on a variety of different medications and combination therapies. This was accounted for by a novel analysis method. CONCLUSION Platelet serotonin levels and content of immunomodulatory compounds are significantly altered in patients with MDD, even if treatment effects are taken into account.

Indications for liver transplantation in adults

SummaryLiver transplantation has emerged as an established and well-accepted therapeutic option for patients with acute and chronic liver failure and hepatocellular carcinoma. The disproportion between recipients and donors is still an ongoing problem that has only been solved partially over the last centuries. For several patients no life-saving organs can be distributed. Therefore, objective and internationally established recommendations regarding indication and organ allocation are imperative. The aim of this article is to establish evidence-based recommendations regarding the evaluation and assessment of adult candidates for liver transplantation. This publication is the first Austrian consensus paper issued and approved by the Austrian Society of Gastroenterology and Hepatology in cooperation with the Austrian Society of Transplantation, Infusion and Genetics.

High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population: implications for genetic testing

Screening for founder mutations in BRCA1 and BRCA2 has been discussed as a cost-effective testing strategy in certain populations. In this study, comprehensive BRCA1 and BRCA2 testing was performed in a routine diagnostic setting. The prevalence of the BRCA1 stop mutation c.4183C>T, p.(Gln1395Ter), was determined in unselected breast and ovarian cancer patients from different regions in the Tyrol. Cancer registry data were used to evaluate the impact of this mutation on regional cancer incidence. The mutation c.4183C>T was detected in 30.4% of hereditary BRCA1-associated breast and ovarian cancer patients in our cohort. It was also identified in 4.1% of unselected (26% of unselected triple negative) Tyrolean breast cancer patients and 6.8% of unselected ovarian cancer patients from the Lower Inn Valley (LIV) region. Cancer incidences showed a region-specific increase in age-stratified breast and ovarian cancer risk with standardized incidence ratios of 1.23 and 2.13, respectively. We, thus, report a Tyrolean BRCA1 founder mutation that correlates to a local increase in the breast and ovarian cancer risks. On the basis of its high prevalence, we suggest that targeted genetic analysis should be offered to all women with breast or ovarian cancer and ancestry from the LIV region.

Homocysteine Biochemistry and Cognitive Decline in the Elderly

To the Editor: Mendonça et al1 present data obtained from the large prospective longitudinal Newcastle 85þ study. In this very old study population, a possible association was investigated between 1carbon metabolism biomarkers (vitamins folate and B12, and homocysteine), and cognitive impairment assessed by the Standardized Mini-Mental State Examination and the attention-specific cognition with the Cognitive Drug Research System at baseline and at several years of follow-up. Compared with participants in the lowest quartile, individuals in the highest quartile of total homocysteine (tHcy) showed lower scores in the Standardized Mini-Mental State Examination, an estimate of global cognition, and only tHcy was associated with the rate of decline in focused attention scores over 3 years. Moreover, red blood cell folate and tHcy, but not plasma vitamin B12, were associatedwith better global cognition. Still the latter were not predictive for the rate of decline over 5 years thereafter. Data imply that folate and homocysteine metabolism are crucial for cognition, but there is residual doubt whether folate deficiency is primary or homocysteine can indeed play a role in the pathogenesis of cognitive decline. In fact, measurement of tHcy is usually accomplished after reduction of homocystine to its reduced form homocysteine, and actually we do not know exactly what the ratio of homocysteine to its oxidized counterpart homocystine is in vivo. Nevertheless, only the chemically reduced form of homocysteine, per se an antioxidant, which however upon exposure to oxygen (O2) can give rise to superoxide anion (O2 ) generation, exerts some influence on cell metabolism, whereas homocysteine is suggested to be merely inert. Interestingly, metabolism of B-vitamins and homocysteine are also intertwined with inflammation and immune activation,2 which could be of greater relevance inneurodegeneration and other chronic disorders. Increased tHcy levels are observed in stimulated human peripheral blood mononuclear cells3 and also in patients suffering from increased immune activation,which is detected by, for example, elevated levels of the macrophage product neopterin) are paralleled by a decline of B-vitamins.2 Supplementationwith B vitamins is able to lower tHcy levels only, but concentrations of immune activation markers like neopterin do not change.4,5 Thus, there is no change of the cardiovascular risk by such a therapeutic approach.6When intake of B-vitamins is kept constant among patients, as it is the case when polytraumatized patients are hospitalized and receive standardized enteral nutrition, nevertheless tHCy levels increase in patients with unfavorable outcome compared with survivors.7

Diagnosis and therapy of cognitive deficits in oncology patients

Improvements in the diagnostics and therapy of almost all types of cancer have extended the survival rates and average life expectancies of oncology patients. As a result the assessment of cognitive deficits is becoming much more important not only in cancer diagnostics but also in the disease-free period following treatment. Various cognitive deficits can occur in patients with intracranial as well as extracranial malignancies. These deficits can be caused by tumor or treatment-related factors. Previous studies have shown that cognitive deficits may negatively influence the quality of life, therapy adherence, prognosis and mortality of patients. Currently, standardized specially designed cognitive tests for oncology patients are lacking; nevertheless, neurocognitive assessment should become an integral element in the diagnostic procedure as well as in the therapeutic process of these patients. An increasing number of studies are currently evaluating pharmacological and non-pharmacological strategies to treat or prevent cognitive deficits; however, recommendations for daily clinical use are still lacking.

[Patients, physicians and nursing personnel in intensive care units : Psychological and psychotherapeutic interventions].

During intensive care treatment patients suffer from various forms of stress. Certain psychological and psychotherapeutic interventions (e. g. cognitive behavior therapy, hypnotherapy and psychoeducation) can provide relief. Even patients with a severely reduced ability to communicate can benefit from an early psychological intervention as supportive treatment. The aim of these interventions is to reduce psychological impairments and burdens, provide strategies for coping with physical handicaps or necessary treatment and avoid long-term negative psychological impacts. Organizational and institutional constraints as well as emotional stress are a specific challenge for intensive care personnel. In order to guarantee an efficient collaboration within an interdisciplinary team it is vital to follow clearly defined methods of communication exchange, such as daily ward rounds, regular multidisciplinary meetings and team or case-focused supervision. Properly functioning teamwork increases job satisfaction and is the key to an optimal therapy for the patients.ZusammenfassungWährend einer intensivmedizinischen Behandlung sind die Patienten zahlreichen Belastungen ausgesetzt, die mittels verschiedenster psychologischer/psychotherapeutischer Maßnahmen (Interventionen aus Verhaltenstherapie, Hypnotherapie, Psychoedukation etc.) reduziert werden können. Auch Patienten, die nur sehr eingeschränkt kontakt- bzw. kommunikationsfähig sind, können von einer bereits frühzeitigen psychologischen Intervention, im Sinne einer supportiven Mitbehandlung profitieren. Ziel dieser Interventionen ist es, psychische Beeinträchtigungen und Belastungen zu reduzieren, Strategien zu vermitteln, um mit körperlichen Einschränkungen bzw. medizinisch notwendigen Behandlungen besser umgehen zu können und langfristig negative psychische Auswirkungen zu vermeiden.Organisatorische und institutionelle Rahmenbedingungen sowie emotionale Belastungen stellen für die Behandlungsteams auf Intensivstationen spezifische Herausforderungen dar. Um eine effektive interdisziplinäre Teamarbeit zu gewährleisten und zu fördern, sind verschiedene Formen des Austausches wie tägliche Visiten, regelmäßige fach- und berufsgruppenübergreifende Besprechungen sowie Team- bzw. Fallsupervision unabdingbar. Funktionierende Teamarbeit bedeutet eine höhere Arbeitszufriedenheit und ist zudem ausschlaggebend für eine optimale Patientenbehandlung.AbstractDuring intensive care treatment patients suffer from various forms of stress. Certain psychological and psychotherapeutic interventions (e. g. cognitive behavior therapy, hypnotherapy and psychoeducation) can provide relief. Even patients with a severely reduced ability to communicate can benefit from an early psychological intervention as supportive treatment. The aim of these interventions is to reduce psychological impairments and burdens, provide strategies for coping with physical handicaps or necessary treatment and avoid long-term negative psychological impacts. Organizational and institutional constraints as well as emotional stress are a specific challenge for intensive care personnel. In order to guarantee an efficient collaboration within an interdisciplinary team it is vital to follow clearly defined methods of communication exchange, such as daily ward rounds, regular multidisciplinary meetings and team or case-focused supervision. Properly functioning teamwork increases job satisfaction and is the key to an optimal therapy for the patients.

Differential changes in platelet reactivity induced by acute physical compared to persistent mental stress

Platelets are important in hemostasis, but also contain adhesion molecules, pro-inflammatory and immune-modulatory compounds, as well as most of the serotonin outside the central nervous system. Dysbalance in the serotonin pathways is involved in the pathogenesis of depressive symptoms. Thus, changes in platelet aggregation and content of bioactive compounds are of interest when investigating physiological stress-related mental processes as well as stress-related psychiatric diseases such as depression. In the present study, a characterization of platelet reactivity in acute physical and persistent mental stress was performed (aggregation, serotonin and serotonin 2A-receptor, P-selectin, CD40 ligand, matrix metalloproteinase-2 and -9 (MMP-2 and -9), platelet/endothelial adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), β-thromboglobulin (β-TG) and platelet factor 4 (PF-4). Acute physical stress increased platelet aggregability while leaving platelet content of bioactive compounds unchanged. Persistent mental stress led to changes in platelet content of bioactive compounds and serotonin 2A-receptor only. The values of most bioactive compounds correlated with each other. Acute physical and persistent mental stress influences platelets through distinct pathways, leading to differential changes in aggregability and content of bioactive compounds.