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Residents of care homes across the globe are affected by the spread of SARS-CoV-2 as they have been identified as a high-risk group and because they experienced strict social isolation regulations during the first wave of the pandemic. Social isolation of older people with poor physical and mental health is strongly associated with mental health problems and decreased life expectancy. Other research has shown that older people managed to adapt to the changes brought about by the pandemic and have linked this to the concept of resilience. The aim of this research project was to investigate how this applied to residents in care home settings during the first phases of the contact ban in Germany from sociology, developmental psychology and environmental gerontology perspectives, and to gain in-depth understanding of residents' experiences. This paper draws on structured interview data collected from residents in two care homes during early June 2020 in Frankfurt am Main, Germany. The findings show that their experiences were shaped by three factors: care home settings and the approach of staff to handling the contact ban; biographical sense of resilience; and a hierarchy of life issues. The findings highlight the importance of locally specific response mechanisms in care homes, agency and belonging of residents despite health-related limitations and the importance of a critical (gendered) lens on understanding their experiences. [ABSTRACT FROM AUTHOR]

Background: The expression of HER2, estrogen (ER) and progesterone (PR) receptor can change during the course of the disease in breast cancer (BC). Therefore, reassessment of these markers at the time of disease progression might help to optimize treatment decisions. In this context, characterization of circulating tumor cells (CTCs) could be of relevance since metastatic tissue may be difficult to obtain for repeated analysis. Here we compared HER2/ER/PR expression profiles of primary tumors, metastases and CTCs.Methods: Ninety-six patients with metastatic BC from seven University BC Centers in Germany were enrolled in this study. Blood was obtained at the time of first diagnosis of metastatic disease or disease progression and analyzed for CTCs using the AdnaTest BreastCancer (QIAGEN Hannover GmbH, Germany) for the expression of EpCAM, MUC-1, HER2, ER and PR. HER2 expression on CTCs was additionally assessed by immunocytochemistry using the CellSearch® assay.Results: The detection rate for CTCs using the AdnaTest was 43 % (36/84 patients) with the expression rates of 50 % for HER2 (18/36 patients), 19 % for ER (7/36 patients) and 8 % for PR (3/36 patients), respectively. Primary tumors and CTCs displayed a concordant HER2, ER and PR status in 59 % (p = 0.262), 39 % (p = 0.51) and 44 % (p = 0.62) of cases, respectively. For metastases and CTCs, the concordance values were 67 % for HER2 (p = 0.04), 43 % for ER (p = 0.16) and 46 % for PR (p = 0.6). Using the CellSearch® assay, the CTC-positivity rate was 53 % (42/79 patients) with HER2 expressed in 29 % (12/42) of the patients. No significant concordance (58 % and 53 %) was found when HER2 on CTCs was compared with HER2 on primary tumors (p = 0.24) and metastases (p = 0.34). Interestingly, primary tumors and metastases were highly concordant for HER2 (84 %, p = 1.13E-08), ER (90 %, p = 3.26E-10) and PR (83 %, p = 2.09E-09) and ER-and PR-positive metastases were significantly found to be of visceral origin (p = 0.03, p = 0.02).Conclusion: Here we demonstrate that the molecular detection of HER2 overexpression in CTC is predictive of the HER2 status on metastases. Detailed analysis of ER and PR expression rates in tissue samples and CTCs may provide useful information for making treatment decisions. [ABSTRACT FROM AUTHOR]

Background/Aims: Mild cognitive impairment (MCI) is a frequent syndrome in the older population, which involves an increased risk to develop Alzheimer's disease (AD). The latter can be modified by the cognitive reserve, which can be operationalized by the length of school education. MCI can be differentiated into four subtypes according to the cognitive domains involved: amnestic MCI, multiple-domain amnestic MCI, non-amnestic MCI and multiple-domain non-amnestic MCI. While neurocognitive deficits are a constituent of the diagnosis of these subtypes, the question of how they refer to the cognitive reserve still needs to be clarified. Methods: We examined neuropsychological deficits in healthy controls, patients with MCI and patients with mild AD (n = 485) derived from a memory clinic. To reduce the number of neuropsychological variables, a factor analysis with varimax rotation was calculated. In a second step, diagnostic groups including MCI subtypes were compared with respect to their clinical and neuropsychological characteristics including cognitive reserve. Results: Most MCI patients showed the amnestic multiple-domain subtype followed by the pure amnestic subtype, while the non-amnestic subtypes were rare. The amnestic subtype displayed a significantly higher level of cognitive reserve and higher MMSE scores than the amnestic multiple-domain subtype, which was in most cases characterized by additional psychomotor and executive deficits. Conclusions: These findings confirm earlier reports revealing that the amnestic multiple-domain subtype is the most frequent one and indicating that a high cognitive reserve may primarily prevent psychomotor and executive deficits in MCI. [ABSTRACT FROM AUTHOR]

Conclusion. Neither elective selective neck dissection nor any conservative treatment option in pT2cN0 glottic cancer showed a significant advantage on survival. This should be the basis for future treatment standardization. Obligatory documentation of the R status and cause of death in the cancer registries will improve the data interpretation in the future. Objectives. Optimal adjuvant treatment of pT2cN0 glottic cancer is not well defined. The impact of neck dissection or radio(chemo)therapy for better outcome is unknown. Methods: In a retrospective cancer registry study we analyzed the survival of 73 patients with pT2cN0 glottic cancer in Thuringia, Germany, treated surgically between 1996 and 2005. Results: In all, 35 patients had undergone elective neck dissection, the remaining 38 patients had not. Histopathology revealed occult lymph node metastasis in three patients. Adjuvant radiotherapy was delivered to 17 patients and radiochemotherapy to 4. Overall, 52 patients received an adjuvant treatment. The 5-year recurrence-free survival rate was 60.8% and the 5-year overall survival rate was 56.5%. Multivariate but not univariate analysis revealed age >62 years ( p == 0.05) and neck dissection ( p == 0.033) as significant negative risk factors for tumor recurrence. Looking at overall survival, the site of primary surgery and radiotherapy were significant univariate risk factors, whereas multivariate analysis did not reveal any independent risk factor. No adjuvant treatment or combinations of adjuvant treatment resulted in better recurrence-free or overall survival ( p == 0.253; p == 0.279). [ABSTRACT FROM AUTHOR]

Background: Depression is the second most common psychiatric illness in old people. Up to 30% of nursing home residents have minor or major depression. Although depressive disorders in old age can be improved and even cured with adequate therapy, they often go unnoticed in nursing home residents and remain untreated. This highlights a striking deficit in health care and might result not only in lower quality of life among those concerned but also in poor physical functioning, premature mortality, and increased hospitalization rates.Methods: The aims of the interdisciplinary research project DAVOS are to implement an innovative and stepped structural case management program to improve depression treatment for nursing home residents by a modularized intervention and to assess it in terms of its effectiveness. Intervention modules are in line with recommendations given by the German national treatment guidelines for depression (S3 guidelines). Ten nursing homes in Frankfurt, Germany, will participate in the project, which aims to recruit a study population of 380. The recruitment will continue throughout the trial (open cohort). Persons (>60 years) who live in a nursing home, have no medical diagnosis of dementia, and can provide their informed consent to participate are eligible for inclusion in the study. Residents with a clinical diagnosis of dementia, alcohol or substance-related disorders, or other serious psychiatric illnesses will be excluded. DAVOS is a controlled cluster-randomized study that employs a stepped-wedge design.Discussion: Our main hypothesis is that the implementation of the intervention will lead to a decline in the prevalence of depression and a reduction in depression symptoms among the home residents. In addition, we expect the intervention to have a positive impact on secondary outcomes such as level of functioning, quality of life, and social participation. The project's results can make an important contribution toward improving the health care of nursing home residents who have late-life depression.Trial Registration: DRKS, DRKS00015686 , Oct. 10, 2018. [ABSTRACT FROM AUTHOR]

Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, a 3-year prospective study, we evaluated a novel diagnostic concept based on multidisciplinary expertise in Germany. Here we present the systematic investigation of the phenotypic and molecular genetic data of 1,577 patients who had undergone exome sequencing and were partially analyzed with next-generation phenotyping approaches. Molecular genetic diagnoses were established in 32% of the patients totaling 370 distinct molecular genetic causes, most with prevalence below 1:50,000. During the diagnostic process, 34 novel and 23 candidate genotype-phenotype associations were identified, mainly in individuals with neurodevelopmental disorders. Sequencing data of the subcohort that consented to computer-assisted analysis of their facial images with GestaltMatcher could be prioritized more efficiently compared with approaches based solely on clinical features and molecular scores. Our study demonstrates the synergy of using next-generation sequencing and phenotyping for diagnosing ultrarare diseases in routine healthcare and discovering novel etiologies by multidisciplinary teams., (© 2024. The Author(s).)

Background: Disease prevention and health promotion in and for old age have become increasingly more important. Nevertheless, more (national) research and implementation in practice is needed, as the international comparison shows., Objective: To develop guiding principles for research and practice on prevention and health promotion in and for old age., Material and Methods: As part of an iterative process, members of the German Society of Gerontology and Geriatrics came together in workshops and symposia to formulate key guiding principles and fields of action for prevention and health promotion., Results: The following were worked out: 1) prevention and health promotion are useful and possible up to oldest age, 2) prevention and health promotion for advanced age should start early, 3) prevention and health promotion must take into account the diversity and heterogeneity of the life situations of old people, 4) prevention and health promotion promote and demand self-determination and participation, 5) prevention of multiple illnesses must be given greater attention, 6) prevention of the need for long-term care and prevention in long-term care must be treated equally, 7) prevention and health promotion must be thought of in terms of life worlds and across sectors, paying particular attention to aspects of social inequality and a focus on resources, 8) prevention and health promotion and the related research must be interdisciplinary and transdisciplinary and be applied at different levels, from molecular to societal., Discussion: The guiding principles outline the focal points of future-oriented ageing, health and healthcare research and open up fields of action but also show the limits of this approach for political decision-makers, researchers and practitioners., (© 2023. The Author(s).)

Evidence-based and comprehensible health information is a key element of evidence-based medicine and public health. The goal is informed decision-making based on realistic estimations of health risks and accurate expectations about benefits and harms of interventions. In Germany, standards of evidence-based risk information were poorly followed during the COVID-19 pandemic. Frequently, public information was biased, fragmentary and misleading. Pandemic-related threat scenarios induced emotional distress and unnecessary anxiety. A systematic and comprehensive evaluation of the pandemic measures is crucial, but still pending in Germany. A critical analysis of risk communication by experts, politicians and the media during the pandemic should be a key element of the evaluation process. Evaluation of decision making and media reporting during the pandemic should improve preparedness for future crises., (Copyright © 2024. Published by Elsevier GmbH.)

The study aimed to assess how dementia researchers view eight support tools that have been defined to enhance informed consent (IC) procedures for people with dementia (PwD). In an online survey, 19 dementia researchers from Germany and Portugal evaluated the tools in terms of 4 implementation criteria. Overall, they all had a very positive attitude towards the support tools, whereby the tools person-centered attitude of the researcher and elaborated plain language were the most highly rated of the eight tools. Our findings also indicated that familiar support tools were assessed more favorably than those that were previously unknown. Overall, the results of this study showed that the participating dementia researchers were open to the use of decision support measures in PwD and were willing to apply the support tools in practice., (© 2020. The Author(s).)

People with dementia often require medical and nursing care and are regularly confronted with the need to make decisions in this respect; however, in practice uncertainty often exists as to whether a person with dementia is capable of providing consent, what procedures should be used to obtain informed consent, how to provide the necessary information and how capacity to consent can be assured. By providing structured practical recommendations, the S2k guidelines "Consent of persons with dementia to medical treatment" (coordinated by the Association of the Scientific Medical Societies of Germany, AWMF, registration number 108-001) provide a first attempt to summarize and update the relevant medical, legal, ethical and psychological requirements that should be satisfied in this respect. This article enables insights into the guidelines and an overview of the most important recommendations.

Predominantly the older population is affected by a severe course of COVID-19. The mortality of hospitalized patients with COVID-19 above the age of 80 years is up to 54% in international studies. These observations indicate the necessity to highlight the geriatric perspective on this disease. The diagnostics and treatment of COVID-19 do not differ between younger and older patients but atypical symptoms should be expected more frequently in old age. Older subjects show an increased need for rehabilitation after COVID-19. Paradoxically, increasing rehabilitation demands go along with a reduced availability of geriatric rehabilitation options, the latter being a consequence of closure or downsizing of rehabilitation departments during the pandemic. In general, measures of isolation and quarantine should be diligently balanced as the health and emotional consequences of such measures may be severe in older persons. In light of the poor prognosis of older COVID-19 patients, advanced care planning becomes even more relevant. Caregivers and physicians should be encouraged to compose advanced care directives that also reflect the specific circumstances of COVID-19. Fortunately, current data suggest that the effectiveness of the vaccination with the mRNA-vaccines approved in Germany may be equally high in older compared to younger persons.

Chronic obstructive pulmonary disease (COPD) is a frequent diagnosis in older individuals and contributor to global morbidity and mortality. Given the link between lung disease and aging, we need to understand how molecular indicators of aging relate to lung function and disease. Using data from the population-based KORA (Cooperative Health Research in the Region of Augsburg) surveys, we associated baseline epigenetic (DNA methylation) age acceleration with incident COPD and lung function. Models were adjusted for age, sex, smoking, height, weight, and baseline lung disease as appropriate. Associations were replicated in the Normative Aging Study. Of 770 KORA participants, 131 developed incident COPD over 7 years. Baseline accelerated epigenetic aging was significantly associated with incident COPD. The change in age acceleration (follow-up - baseline) was more strongly associated with COPD than baseline aging alone. The association between the change in age acceleration between baseline and follow-up and incident COPD replicated in the Normative Aging Study. Associations with spirometric lung function parameters were weaker than those with COPD, but a meta-analysis of both cohorts provide suggestive evidence of associations. Accelerated epigenetic aging, both baseline measures and changes over time, may be a risk factor for COPD and reduced lung function.

Circulating tumor cell (CTC) detection is a prognostic factor in the metastatic breast cancer (MBC) setting. Discrepancies in primary (PT) and metastatic tumor (MT) genetic profiles are also of prognostic importance. Our study aimed to compare the CTC statuses and prognoses between those with subtype stable MBCs and MBCs with specific biomarker conversions. The study enrolled 261 MBC patients, treated at the National Center for Tumor Diseases, Heidelberg, Germany in a five-year period. All underwent PT and MT biopsies and subsequent CTC enumeration before the initiation of systemic therapy. ER and HER2 statuses of the PTs and MTs were determined and progression free survivals (PFSs) and overall survivals (OSs) were recorded. We compared CTC statuses, CTC counts, PFSs and OSs between subgroups of patients with different receptor change patterns. Patients who had tumors that converted to triple negative MTs had the shortest median OSs, while HER2 expression was not associated with a shorter median OS. No significant differences in PFSs and OSs have been demonstrated by Kaplan-Meier curve comparisons in any of the subgroup analyses. CTC counts were similar in all subgroups. CTCs were comparably less frequently detected in patients with a stable HER2 expression. Similar proportions of CTC positives were observed in all other subtype change pattern subgroups, barring the aforementioned HER2 stable subgroup. The detection of CTCs was of no appreciable prognostic value in different receptor change pattern subgroups in our cohort.

The Hamburg City Health Study (HCHS) is a large, prospective, long-term, population-based cohort study and a unique research platform and network to obtain substantial knowledge about several important risk and prognostic factors in major chronic diseases. A random sample of 45,000 participants between 45 and 74 years of age from the general population of Hamburg, Germany, are taking part in an extensive baseline assessment at one dedicated study center. Participants undergo 13 validated and 5 novel examinations primarily targeting major organ system function and structures including extensive imaging examinations. The protocol includes validate self-reports via questionnaires regarding lifestyle and environmental conditions, dietary habits, physical condition and activity, sexual dysfunction, professional life, psychosocial context and burden, quality of life, digital media use, occupational, medical and family history as well as healthcare utilization. The assessment is completed by genomic and proteomic characterization. Beyond the identification of classical risk factors for major chronic diseases and survivorship, the core intention is to gather valid prevalence and incidence, and to develop complex models predicting health outcomes based on a multitude of examination data, imaging, biomarker, psychosocial and behavioral assessments. Participants at risk for coronary artery disease, atrial fibrillation, heart failure, stroke and dementia are invited for a visit to conduct an additional MRI examination of either heart or brain. Endpoint assessment of the overall sample will be completed through repeated follow-up examinations and surveys as well as related individual routine data from involved health and pension insurances. The study is targeting the complex relationship between biologic and psychosocial risk and resilience factors, chronic disease, health care use, survivorship and health as well as favorable and bad prognosis within a unique, large-scale long-term assessment with the perspective of further examinations after 6 years in a representative European metropolitan population.

Background: It has been questioned by researchers in robotics as well in the general public to what extent companion-type robots can support the elderly with the fulfillment of their psychological and social needs. Although these robots have already been used in care settings in Germany, research has referred little to this practical experience in order to analyze their impact and benefit. To start to close this gap, the current article reports on the current use of companion-type robots in care settings, on the effects reported by professional caregivers as well as on the role of psychosocial needs in the acceptance and use of companion-type robots by the elderly., Material and Methods: In the first study, 30 professional caregivers with experience in the use of the robot seal Paro in care settings were interviewed regarding Paro's application and the observed effects on their clients. In the second study, three case examples are presented from an interaction study in which vulnerable elderly persons had the robot dinosaur Pleo at their disposal for a maximum period of 15 days., Results: Paro is used very flexibly in a variety of settings and with a broad range of user groups (study 1). The reported psychosocial effects were mainly positive but short term. The case examples (study 2) show that psychosocial needs can both foster or hinder robot acceptance and use. They also emphasize the important role of caregivers in the interaction between the elderly and emotional robots in the context of eldercare., Conclusion: The beneficial and ethical use of companion-type robots in care settings demands a high commitment on the part of the caregivers. Given this prerequisite, emotional robots can be a valuable therapeutic tool.

Background: The use of assessment tools has been shown to improve the inter-rater reliability of capacity assessments. However, instrument-based capacity assessments of people with dementia face challenges. In dementia research, measuring capacity with instruments like the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) mostly employ hypothetical treatment vignettes that can overwhelm the abstraction capabilities of people with dementia and are thus not always suitable for this target group. The primary aim of this study was to provide a standardized real informed consent paradigm that enables the dementia-specific properties of capacity to consent to treatment in people with dementia to be identified in a real informed consent process that is both externally valid and ethically justifiable., Methods: The sample consisted of 53 people with mild to moderate dementia and a group of 133 people without cognitive impairment. Rather than using a hypothetical treatment vignette, we used a standardized version of the MacCAT-T to assess capacity to consent to treatment with cholinesterase inhibitors in people with dementia. Inter-rater reliability, item statistics, and psychometric properties were also investigated., Results: Intraclass correlations (ICCs) (0.951-0.990) indicated high inter-rater reliability of the standardized real informed consent paradigm. In the dementia group, performance on different items of the MacCAT-T varied. Most people with dementia were able to express a treatment choice, and were aware of the need to take a tablet. Further information on the course of the disorder and the benefits and risks of the treatment were less understood, as was comparative reasoning regarding treatment alternatives., Conclusion: The standardized real informed consent paradigm enabled us to detect dementia-specific characteristics of patients' capacity to consent to treatment with cholinesterase inhibitors. In order to determine suitable enhanced consent procedures for this treatment, we recommend the consideration of MacCAT-T results on an item level. People with dementia seem to understand only basic information. Our data indicate that one useful strategy to enhance capacity to consent is to reduce attention and memory demands as far as possible.

Background: Failures of communication between professional caregivers and physicians affect the quality of supply of nursing home residents., Aim: As part of a model project it was aimed to develop a training for caregivers to improve communication and promote cooperation with physicians., Methods: For the needs assessment as a basis to develop the training 56 professional caregivers and 40 physicians engaged in nursing home care answered questionnaires regarding their cooperation. Based on these results a module for communication between professional caregivers and physicians was developed and adapted the TANDEM communication training for caregivers by Haberstroh and Pantel (2011). 25 professional caregivers in leading positions have been trained as multipliers in order to provide their colleagues the communication training with the additional element (TANDEMplus). TANDEMplus was evaluated in forms of reflection rounds and feedback questionnaires., Results: 254 professional caregivers, housekeeping staff and daytime companions participated in a complete TANDEMplus training by the multipliers until July 2014. The implementation of their developed communication strategies into practice was experienced positively by the participants., Conclusions: The module “communication with physicians” is relevant for professional caregivers to raise awareness of their own competence and facilitate a structured information exchange at eye level. The training of multipliers was executed in order to ensure transfer effects and sustainability.

Interactions between cancer cells and microenvironment are emerging issue in tumor progression. Aldehyde dehydrogenase 1 (ALDH1) is a recognized cancer stem cell marker but little is known about its role in intratumoral stroma. Therefore, we focused on ALDH1 expression in tumor-associated stroma of breast carcinomas (BrCa). Stromal and tumoral ALDH1 expression was evaluated immunohistochemically in BrCa and their lymph node metastases (LNMs), and related to clinico-pathological characteristics, patients' outcome, presence of CD68, HLADR, retinoic acid (RA) in stroma, and selected proteins in tumor cells. ALDH1(+) stromal cells were detected in 53% of 374 BrCa and 61% of 102 LNMs. ALDH1(+) stroma in primary tumor correlated to longer disease-free (p = 0.030), metastasis-free (p = 0.024), and overall survival (p = 0.043) having an independent prognostic impact on DFS (multivariate analysis, p = 0.047). It was associated with concomitant presence of HLA-DR(+) stromal cells and RA in tumor cells (both p < 0.001), and inversely associated with vimentin expression in tumor cells (p = 0.036). ALDH1(+) stroma in LNMs correlated inversely to presence of disseminated tumor cells in patients' bone marrow (p = 0.014) and was independent prognosticator of shorter DFS and MFS (multivariate analysis, p = 0.004 and p = 0.002, respectively). In conclusion, ALDH1 expression in tumor-associated stromal cells indicates reduced BrCa progression, possibly via RA secretion.

Background: Preliminary research has suggested the potential prognostic value of circulating tumor cells (CTC) in patients with advanced nonmetastatic urothelial carcinoma of the bladder (UCB)., Objective: Prospectively analyze the clinical relevance and human epidermal growth factor receptor 2 (HER2) expression of CTC in patients with clinically nonmetastatic UCB., Design, Setting, and Participants: Blood samples from 100 consecutive UCB patients treated with radical cystectomy (RC) were investigated for the presence (CellSearch system) of CTC and their HER2 expression status (immunohistochemistry). HER2 expression of the corresponding primary tumors and lymph node metastasis were analyzed using fluorescence in situ hybridization., Intervention: Blood samples were taken preoperatively. Patients underwent RC with lymphadenectomy., Measurements: Outcomes were assessed according to CTC status. HER2 expression of CTC was compared with that of the corresponding primary tumor and lymph node metastasis., Results and Limitations: CTC were detected in 23 of 100 patients (23%) with nonmetastatic UCB (median: 1; range: 1-100). Presence, number, and HER2 status of CTC were not associated with clinicopathologic features. CTC-positive patients had significantly higher risks of disease recurrence and cancer-specific and overall mortality (p values: ≤ 0.001). After adjusting for effects of standard clinicopathologic features, CTC positivity remained an independent predictor for all end points (hazard ratios: 4.6, 5.2, and 3.5, respectively; p values ≤ 0.003). HER2 was strongly positive in CTC from 3 of 22 patients (14%). There was discordance between HER2 expression on CTC and HER2 gene amplification status of the primary tumors in 23% of cases but concordance between CTC, primary tumors, and lymph node metastases in all CTC-positive cases (100%). The study was limited by its sample size., Conclusions: Preoperative CTC are already detectable in almost a quarter of patients with clinically nonmetastatic UCB treated with RC and were a powerful predictor of early disease recurrence and cancer-specific and overall mortality. Thus CTC may serve as an indication for multimodal therapy. Molecular characterization of CTC may serve as a liquid biopsy to guide individual targeted therapy in future clinical trials., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Breast cancer is the most frequent cancer and the leading cause of cancer-related deaths in women worldwide. The prognosis of breast cancer is tightly correlated with the degree of spread beyond the primary tumour. Arachidonic acid (AA) and prostaglandin E(2) (PGE(2)) are known to regulate tumour metastasis enabling epithelial-mesenchymal transition (EMT). However, the detailed role of 15-hydroxyprostaglandin dehydrogenase (HPGD), the key enzyme degrading prostaglandin E(2) , remains unclear in breast cancer. Here, we show that HPGD mRNA is overexpressed in a subset of clinical breast cancers compared to normal breast tissue samples and that high HPGD mRNA expression associates with poor prognosis. Immunohistochemical staining of primary breast cancer and lymph node metastasis tissue samples confirmed high HPGD protein expression in 20% of the samples, as well as associated HPGD expression with aggressive characteristics, such as increased risk of disease relapse and shorter disease-free survival. Results from cultured cells indicated abundant HPGD expression in highly metastatic breast cancer cells, and impairment of HPGD expression using RNA interference led to a significant decrease in transforming growth factor-β signalling, in cellular arachidonic acid levels as well as in cell migration. Furthermore, gene expression microarray analysis followed by quantitative RT-PCR validation showed that HPGD silencing decreased aryl hydrocarbon receptor signalling and induced mesenchymal-epithelial transition. In conclusion, our results indicate that HPGD is highly expressed in metastatic and aggressive breast cancer and promotes EMT and migration in breast cancer cells., (Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Laryngeal cancer is one of the most frequent types of head and neck cancer. The incidence is decreasing for men but still increasing for women. The incidence in Germany is about 5-7/100,000 persons/year for men and 0.6-0.8/100,000 persons/year for women. Due to the increased life expectancy, the average age of patients diagnosed with laryngeal cancer is increasing. Nevertheless, adequately prepared older patients treated by standard protocols can have the same survival and complication rates as younger patients. Tobacco and alcohol are still the primary risk factors responsible for disease in at least 80% of the patients. Despite the many new diagnostic tools, still more than half of the patients are diagnosed at an advanced tumor stage. Survival rates have not improved significantly in the last 10 years in Germany, and the average 5-year overall survival rate is about 60%. However, a decrease in the survival rate, as observed in the USA, cannot be confirmed for Germany.

Objectives: Dementia increasingly diminishes the ability to communicate. We aimed to develop and evaluate a psychosocial intervention program that focuses on communication in dementia care. This was intended to enhance the quality of life (QoL) of people with dementia and to reduce the burden on their informal caregivers., Method: A training program for informal caregivers of people with dementia was developed. The training combines the expertise of geriatric psychiatry, geriatric care, and educational psychology. Caregivers acquire and deepen competencies required to improve communication in dementia care. The training was evaluated with a pre-post-control group design and time-series analyses. Twenty-four informal caregivers participated in the study., Results: The results of the study provide evidence that TANDEM training increases caregivers' use of strategies that are relevant for communication in dementia care and the care receivers' QoL., Conclusion: The results of research in this program show the relevance of including caregivers in interventions and the importance of communication for the QoL of people with dementia.

Purpose: As HER2 status is a strong predictor of the response to trastuzumab, clinical guidelines recommend that all breast tumours are first evaluated for HER2 protein expression by immunohistochemistry (IHC) followed by confirmatory testing for HER2 gene amplification using fluorescence in situ hybridisation (FISH) for 2+ cases. Alternatively, chromogenic in situ hybridisation (CISH) offers a simpler, less expensive approach to detect HER2 amplification., Methods: In this prospective, multi-centre study, based on the largest dataset for HER2 testing in Germany to date, we evaluated the concordance between FISH and CISH in 399 samples from adjuvant and metastatic breast cancer patients. Tumour specimens from routine diagnostic practice were analysed by IHC, FISH and CISH in four reference centres., Results: FISH and CISH results were strongly concordant (κ = 0.83), with 95% of cases showing agreement. Despite variable IHC scoring across testing centres, complete consensus among the three methods was observed for 246 cases, representing 91% of all IHC positive (3+) or negative (0/1+) cases. Confirmatory testing of 132 IHC equivocal (2+) cases also yielded highly concordant results between FISH and CISH., Conclusions: These data validate CISH for the assessment of HER2 gene amplification in breast tumours and, confirm CISH as a valid alternative to FISH in HER2 testing.

There is a growing body of evidence that HER2 status can change during disease recurrence or progression in breast cancer patients. In this context, re-evaluation of HER2 status by assessment of HER2 expression on circulating tumor cells (CTCs) is a strategy with potential clinical application. The aim of this trial was to determine the HER2 status of CTCs in metastatic breast cancer patients comparing two CTC assays. A total of 254 patients with metastatic breast cancer from nine German university breast cancer centers were enrolled in this prospective study. HER2 status of CTCs was assessed using both the FDA-approved CellSearch® assay and AdnaTest BreastCancer™. Using the CellSearch assay, 122 of 245 (50%) patients had ≥5 CTCs, and HER2-positive CTCs were observed in 50 (41%) of these patients. Ninety of 229 (39%) patients were CTC positive using AdnaTest BreastCancer, and HER2 positivity rate was 47% (42 of 90). The rate of breast cancer patients with HER2-negative primary tumors but HER2-positive CTCs was 32% (25 of 78) and 49% (28 of 57) using the CellSearch assay and AdnaTest BreastCancer, respectively. Considering only those patients who had CTCs on both tests (n = 62), concordant results regarding HER2 positivity were obtained in 50% of the patients (31/62) (P = 0.96, κ = -0.006). HER2-positive CTCs can be detected in a relevant number of patients with HER2 negative primary tumors. Therefore, it will be mandatory to correlate the assay-dependent HER2 status of CTCs to the clinical response on HER2-targeted therapies.

In this report, we present the results of a multicenter study to test analytic and diagnostic performance of soluble forms of amyloid precursor proteins alpha and beta (sAPP alpha and sAPP beta) in the cerebrospinal fluid (CSF) of patients with different forms of dementing conditions. CSF samples were collected from 188 patients with early dementia (mini-mental state examination >or=20 in majority of cases) and mild cognitive impairment (MCI) in 12 gerontopsychiatric centers, and the clinical diagnoses were supported by neurochemical dementia diagnostic (NDD) tools: CSF amyloid beta peptides, Tau and phospho-Tau. sAPP alpha and sAPP beta were measured with multiplexing method based on electrochemiluminescence. sAPP alpha and sAPP beta CSF concentrations correlated with each other with very high correlation ratio (R=0.96, P<0.001). We observed highly significantly increased sAPP alpha and sAPP beta CSF concentrations in patients with NDD characteristic for Alzheimer's disease (AD) compared to those with NDD negative results. sAPP alpha and sAPP beta highly significantly separated patients with AD, whose diagnosis was supported by NDD findings (sAPP alpha: cutoff, 117.4 ng ml(-1), sensitivity, 68%, specificity, 85%, P<0.001; sAPP beta: cutoff, 181.8 ng ml(-1), sensitivity, 75%, specificity, 85%, P<0.001), from the patients clinically assessed as having other dementias and supported by NDD untypical for AD. We conclude sAPP alpha and sAPP beta might be regarded as novel promising biomarkers supporting the clinical diagnosis of AD.

The purpose of this study was to develop and evaluate a skill training aimed at increasing the social competence of caregivers of nursing home residents suffering from dementia. Herewith, the professional burden and occupational stress of the caregivers should be reduced and the quality of life of dementia patients should be increased. The contents of the training focused on problems and strategies in the communication with dementia patients and the communication with colleagues. The effectiveness of the intervention was tested in a controlled training study using a multiple control group design and process measurement. The participants of the trainings were 53 nursing home professionals, who were in daily contact with residents suffering from dementia. The results of the study verify effects for all relevant variables. The "social competence" of the caregivers increased and their "work stress" decreased while the "quality of life of dementia patients" increased. Therefore it can be concluded that training the social competence of nursing home professionals is a method to indirectly reduce their work stress and support dementia patients. The results of research in this program underline very clearly that the developed training is an effective option to improve the situation of dementia care in nursing homes. To make the intervention widely applicable we are currently developing a "multiplier program" in a follow-up project.

Background: The German Dementia Competence Network (DCN) has established procedures for standardized multicenter acquisition of clinical, biological and imaging data, for centralized data management, and for the evaluation of new treatments., Methods: A longitudinal cohort study was set up for patients with mild cognitive impairment (MCI), patients with mild dementia and control subjects. The aims were to establish the diagnostic, differential diagnostic and prognostic power of a range of clinical, laboratory and imaging methods. Furthermore, 2 clinical trials were conducted with patients suffering from MCI and mild to moderate Alzheimer's Disease (AD). These trials aimed at evaluating the efficacy and safety of the combination of galantamine and memantine versus galantamine alone., Results: Here, we report on the scope and projects of the DCN, the methods that were employed, the composition and flow within the diverse groups of patients and control persons and on the clinical and neuropsychological baseline characteristics of the group of 2,113 subjects who participated in the observational and clinical trials., Conclusion: These data have an impact on the procedures for the early and differential clinical diagnosis of dementias, the current standard treatment of AD as well as on future clinical trials in AD.

The program Kommunikations-TAnDem was developed with the primary purpose of increasing the communication competence of family caregivers of dementia patients. Further aims were to reduce the burden of family caregivers and to increase the quality of life of dementia patients. The effectiveness of the Kommunikations-TAnDem was tested in a controlled training study with 22 participants using a waiting-group control design and process measurement. The results of the study verify effects for the variables "Communication competence", "Caregivers knowledge about communication in dementia", "Quality of life of dementia patients" and "Directly perceived burden of family caregivers. Therefore it can be concluded that the Kommunikations-TAnDem is a method of indirectly supporting dementia patients by training the family caregivers. The results of research in this program underline very clearly the relevance of the inclusion of the family caregivers in intervention programs and the importance of communication competence for the well-being of dementia patients and their caregivers.

Objective: "Mild cognitive impairment" refers to cognitive deficits in older age that exceed age-related cognitive decline but do not fulfill criteria for dementia. Affected subjects are assumed to be at higher risk for the development of dementia, such as Alzheimer's disease. However, little is known about the group of young-old subjects with respect to the prevalence and natural course of cognitive decline., Method: Within the population-based Interdisciplinary Longitudinal Study on Adult Development and Aging, neuropsychological functioning was assessed in 500 community-dwelling young-old subjects of two German urban regions who were born during 1930-1932. The participants were carefully screened for physical and mental health and reexamined 4 years later. The concept of "aging-associated cognitive decline" was applied., Results: At baseline, 13.4% of the subjects fulfilled criteria for aging-associated cognitive decline. Four years later, the prevalence rates for rose to 23.6%; 52.3% of the subjects initially classified as having aging-associated cognitive decline retained the diagnosis at follow-up. Although subjects with aging-associated cognitive decline showed a reduced performance in all neuropsychological domains addressed, a significant decline was confined to delayed verbal memory test performance during the 4-year follow-up period in relation to comparison subjects. Aging-associated cognitive decline did not predict conversion to dementia during the follow-up interval., Conclusions: In young-old community-dwelling individuals, aging-associated cognitive decline is a frequent condition with a high temporal stability. During a 4-year follow-up, subjects with aging-associated cognitive decline deteriorated specifically in measures of episodic memory, underscoring the value of the respective deficits in characterizing "mild cognitive impairment."

To investigate the psychometric properties of the German version of the CERAD-NP, neuropsychological deficits were compared between 49 patients with mild cognitive impairment (MCI), 80 patients with Alzheimer's disease (AD), 36 with major depression (MD), and 26 elderly controls. All participants were outpatients of the memory clinic of the Section of Geriatric Psychiatry, Heidelberg University. Diagnoses were established based on clinical examination, laboratory testing, neuroimaging, and routine neuropsychological testing according to the criteria of aging-associated cognitive decline (AACD) for MCI, NINCDS-ADRDA for AD, and DSM-IV for MD, respectively. All CERAD-NP subtests discriminated between controls and AD patients with the latter showing significantly (p< or = 0.05) lower test scores. The subtests verbal fluency and constructive apraxia differed significantly between mildly and moderately AD, while the subtests assessing declarative (epsisodic) memory performance showed only minor, non-significant differences between the respective groups. The LKB patients took an intermediate position between controls and AD patients with significantly lower scores in verbal fluency and declarative memory performance than the controls. When compared with the AD patients, MCI patients were significantly impaired in all subtests except constructive apraxia. Relative to the controls, the patients with MD showed a decreased episodic memory performance but no evidence suggesting an impairment in other neuropsychological domains. Our results indicate that the CERAD-NP is a psychometric instrument which allows a sensitive discrimination between mild and moderate AD, MCI, MD and healthy controls. However, sensitivity of discrimination between different stages of dementia varies with respect to the different subtest. While the subtest for episodic memory showed floor effects already for mild dementia, subtests for verbal fluency and constructive apraxia were able to discriminate even between more advanced stages of the disease.

Purpose: There is an urgent need for markers that can predict the efficacy of adjuvant chemotherapy in patients with solid tumors. This study was designed to evaluate whether monitoring of micrometastases in bone marrow can predict the response to systemic chemotherapy in breast cancer., Patients and Methods: Bone marrow aspirates of 59 newly diagnosed breast cancer patients with either inflammatory (n = 23) or advanced (> four nodes involved) disease (n = 36) were examined immunocytochemically with the monoclonal anticytokeratin (CK) antibody A45-B/B3 (murine immunoglobulin G(1); Micromet, Munich, Germany) before and after chemotherapy with taxanes and anthracyclines., Results: Of 59 patients, 29 (49.2%) and 26 (44.1%) presented with CK-positive tumor cells in bone marrow before and after chemotherapy, respectively. After chemotherapy, less than half of the previously CK-positive patients (14 of 29 patients; 48.3%) had a CK-negative bone marrow finding, and 11 (36. 7%) of 30 previously CK-negative patients were CK-positive. At a median follow-up of 19 months (range, 6 to 39 months), Kaplan-Meier analysis of 55 assessable patients revealed a significantly reduced overall survival (P =.011; log-rank test) if CK-positive cells were detected after chemotherapy. In multivariate analysis, the presence of CK-positive tumor cells in bone marrow after chemotherapy was an independent predictor for reduced overall survival (relative risk = 5.0; P =.016)., Conclusion: The cytotoxic agents currently used for chemotherapy in high-risk breast cancer patients do not completely eliminate CK-positive tumor cells in bone marrow. The presence of these tumor cells after chemotherapy is associated with poor prognosis. Thus, bone marrow monitoring might help predict the response to systemic chemotherapy.

Recent scientific and economic developments have emphasized the need for objective and operationalized criteria for the evaluation of collective and individual research performance. In this context the present article discusses the possibilities and limitations of bibliometric analysis in the evaluation of psychiatric research. Taking into account recent scientometric knowledge, the potentials and pitfalls of the so called impact factor are critically discussed with respect to its usefulness in the evaluation of psychiatric research performance in Germany. A major criticism arises from the observation that the unreflecting use of the impact factor may overemphasize quantitative aspects to the disadvantage of qualitative aspects of research. This may however lead to unwanted distortions and misjudgements. The critical analysis of the current use of scientometric indices in the evaluation process emphasizes the need for alternative criteria, which should take into account disciplinary as well as national idiosyncrasis. Accordingly, the authors aim to induce and contribute to a discussion process within the scientific community, which may lead to a more appropriate evaluation of psychiatric research performance.

The term "mild cognitive impairment" refers to cognitive deficits which exceed normal physiological aging processes, but do not fulfill the criteria for dementia. The prevalence rates of four current concepts were compared in a sample of 202 healthy 60-64 year-old participants recruited from the interdisciplinary longitudinal study on adult development and aging (ILSE). Furthermore, the relationships between cognitive deficits and psychological and sociodemographic variables were examined. The following prevalence rates were determined: 13.5% for age-associated memory impairment, 6.5% for age-consistent memory impairment, 1.5% for late-life forgetfulness and 23.5% for aging-associated cognitive decline. Subjective cognitive complaints did not correlate with results obtained from neuropsychological tests. Significant correlations were however found between subjective cognitive complaints and higher scores on depression and neuroticism scales. Significant correlations were also found between a reduced test performance and a lower educational level and socioeconomic status. Longitudinal studies are warranted to further elucidate the predictive value of these diagnostic concepts.

The term "mild cognitive impairment" refers to cognitive deficits which exceed normal physiological aging processes, but do not fulfill the criteria for dementia. While recent studies indicate that the respective deficits can be reliably assessed, different diagnostic criteria have prevented a wide application of this diagnosis in clinical practice. The aims of the present study were (1) to assess the prevalence rates of four current diagnostic concepts and (2) to investigate mild cognitive impairment with respect to psychological and sociodemographic variables. Data from 202 probands recruited from the interdisciplinary longitudinal study on adult development were analyzed. On the time of examination, probands were between 60 to 64 years old and in a good health. The following prevalence rates were determined: 13.5% for age-associated memory impairment (AAMI), 6.5% for age-consistent memory impairment (ACMI), 1.5% for late-life forgetfulness (LLF), and 23.5% for aging-associated cognitive decline (AACD). Complaints of cognitive deficits were significantly correlated with higher scores on depression and neuroticism scales but with none of the neuropsychological measures. Reduced performance in neuropsychological tests was associated with a lower educational level and socioeconomic status. We conclude that the prevalence rates of mild cognitive impairment are highly dependent on the diagnostic criteria applied. In this respect the self-report of cognitive decline might be a less useful criteria. Longitudinal studies are warranted to further elucidate the predictive value of these diagnostic criteria.

Although Germany was a center of neurological research during the 19th century institutionalisation of clinical neurology was delayed in comparison to other countries. The establishment of neurology in Germany is characterised by a conflict between internists, psychiatrists and neurologists that lasted nearly a hundred years. The present study describes and analyses the motives and the course of development of this dispute. The conflict could not be solved by means of objective arguments because on the one hand nervous disease were part of internal medicine, while on the other hand the postulated identity of mental and nervous disease was the central paradigm of the academic psychiatrists. As a professional group the entry of the neurologists into the dispute was very late at a time point when the historical development was already in favour of the psychiatrists. By taking into account not only intrascientific but also political and economic factors, the dynamics of the historical process becomes comprehensible.

During the 20th century clinical neurology developed to a fully established discipline being descended from Psychiatry and Internal Medicine. In this paper the development of clinical neurology at the University of Heidelberg from a Nervenabteilung at the clinic for internal medicine to a chair with separate clinic of neurology is outlined as an example for the controversy which accompanied the institutionalization of the discipline in Germany. Pointing out motives and arguments of the persons involved in this process the specific circumstances of the development of neurology in Germany are stated more precisely.

The institutionalization of an academic discipline in the university system is a complex process influenced by several intra- and extrascientific, personal and economic factors. Starting with pathological anatomy at the beginning of the 19th century, we analysed its development from a subsidiary to a fully established discipline. We ascertained different stages of institutionalization:lectureship, associate chair, chair, institute. At each stage we found supporting as well as hindering factors. It could be shown that the structure of the German academic system was especially conductive to the establishment of the new discipline.