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Non-sedating H1-antihistamines are the recommended first-line treatment for chronic spontaneous urticaria. While efficacy studies usually apply continuous daily treatment regimens, many patients take their medication on demand. In this randomized, double-blind trial we tested whether on-demand H1-antihistamine desloratadine in standard and higher doses is able to improve the resolution of existing wheals. Symptoms of 29 patients with chronic spontaneous urticaria were followed without treatment on one day and again on another day during the next 3 weeks after a single dose of either 5 mg or 20 mg desloratadine, using different objective measures. While the intervention with both doses of desloratadine was effective in terms of a reduction in hyperthermic skin area, there was no improvement in wheal area and wheal volume compared with no treatment. Wheal numbers were reduced after treatment with 20 mg, but not 5 mg, desloratadine. In conclusion, the beneficial effects of non-sedating H1-anti-histamines given on demand appear to be low. Thus, a preventive treatment strategy should be preferred in chronic spontaneous urticaria.

To evaluate outcome in respect to local treatment strategies in 4 prospective CWS trials in patients with paratesticular rhabdomyosarcoma (PTRMS).PTRMS patients have a high number of surgical treatment failures. Retroperitoneal lymph node (LN) involvement is common in patients more than 10 years, and the optimal treatment is unknown.A total of 173 patients with diagnosis of PTRMS were enrolled. Of these, 26 were excluded and 147 patients were finally analyzed. All patients were treated according to the Cooperative Soft Tissue Sarcoma (CWS) trial protocols.The 5-year overall survival was 95.5%, and the 5-year event-free survival (EFS) was 89.8%. Positive predictive factors for EFS were age younger than 10 years and tumor size less than 5 cm. Surgical treatment failures were observed in 34 of 135 patients undergoing primary resection. Primary inguinal/iliacal LN sampling was carried out in 15 of 147 patients with no impact on the EFS (87.5%; P = 0.666). Secondary retroperitoneal LN dissection was done in 32 of 147 patients, of which only 8 patients had viable tumor and a worse outcome (EFS: 50%; P = 0.01). Loco-regional, combined, and metastatic relapses were observed in 13 of 147 patients.The outcome of PTRMS patients is excellent and is hardly improvable. Positive predictors for outcome are age younger than 10 years and tumor size less than 5 cm. Primary LN sampling seems to have no impact on the EFS and should not be recommended. Inadequate surgery can be avoided by treatment in specialized centers. Secondary retroperitoneal LN dissection revealed a high number of unnecessary procedures, but patients with positive LN had a poor prognosis and require additional local therapy.

Objective To evaluate whether invasive coronary angiography or computed tomography (CT) should be performed in patients clinically referred for coronary angiography with an intermediate probability of coronary artery disease. Design Prospective randomised single centre trial. Setting University hospital in Germany. Participants 340 patients with suspected coronary artery disease and a clinical indication for coronary angiography on the basis of atypical angina or chest pain. Interventions 168 patients were randomised to CT and 172 to coronary angiography. After randomisation one patient declined CT and 10 patients declined coronary angiography, leaving 167 patients (88 women) and 162 patients (78 women) for analysis. Allocation could not be blinded, but blinded independent investigators assessed outcomes. Main outcome measure The primary outcome measure was major procedural complications within 48 hours of the last procedure related to CT or angiography. Results Cardiac CT reduced the need for coronary angiography from 100% to 14% (95% confidence interval 9% to 20%, P

Background Plasmodium infection and malaria in school children are increasingly recognized as a relevant public health problem, but data on actual prevalence and health consequences are insufficient. The present study from highland southern Rwanda aimed at estimating infection prevalence among children attending school, at identifying associated factors and at assessing the clinical consequences of these infections. Methods In a survey including 12 schools in the Huye district of Rwanda, 1089 children aged 6–10 years were clinically and anthropometrically examined, malaria parasites were diagnosed by microscopy and PCR, haemoglobin concentrations were measured, and socio- economic and behavioural parameters as well as medical histories were obtained. Results Upon examination, the vast majority of children was asymptomatic (fever 2.7%). Plasmodium infection was detected in 22.4% (Plasmodium falciparum, 18.8%); 41% of these were submicroscopic. Independent predictors of infection included low altitude, higher age, preceding antimalarial treatment, and absence of electricity or a bicycle in the household. Plasmodium infection was associated with anaemia (mean haemoglobin difference of −1.2 g/dL; 95% CI, −0.8 to −1.5 g/dL), fever, underweight, clinically assessed malnutrition and histories of fever, tiredness, weakness, poor appetite, abdominal pain, and vomiting. With the exception of underweight, these conditions were also increased at submicroscopic infection. Conclusion Malaria infection is frequent among children attending school in southern highland Rwanda. Although seemingly asymptomatic in the vast majority of cases, infection is associated with a number of non-specific symptoms in the children´s histories, in addition to the impact on anaemia. This argues for improved malaria surveillance and control activities among school children.

Summary Background Treatment guidelines for aphasia recommend intensive speech and language therapy for chronic (≥6 months) aphasia after stroke, but large-scale, class 1 randomised controlled trials on treatment effectiveness are scarce. We aimed to examine whether 3 weeks of intensive speech and language therapy under routine clinical conditions improved verbal communication in daily-life situations in people with chronic aphasia after stroke. Methods In this multicentre, parallel group, superiority, open-label, blinded-endpoint, randomised controlled trial, patients aged 70 years or younger with aphasia after stroke lasting for 6 months or more were recruited from 19 inpatient or outpatient rehabilitation centres in Germany. An external biostatistician used a computer-generated permuted block randomisation method, stratified by treatment centre, to randomly assign participants to either 3 weeks or more of intensive speech and language therapy (≥10 h per week) or 3 weeks deferral of intensive speech and language therapy. The primary endpoint was between-group difference in the change in verbal communication effectiveness in everyday life scenarios (Amsterdam–Nijmegen Everyday Language Test A-scale) from baseline to immediately after 3 weeks of treatment or treatment deferral. All analyses were done using the modified intention-to-treat population (those who received 1 day or more of intensive treatment or treatment deferral). This study is registered with ClinicalTrials.gov, number NCT01540383. Findings We randomly assigned 158 patients between April 1, 2012, and May 31, 2014. The modified intention-to-treat population comprised 156 patients (78 per group). Verbal communication was significantly improved from baseline to after intensive speech and language treatment (mean difference 2·61 points [SD 4·94]; 95% CI 1·49 to 3·72), but not from baseline to after treatment deferral (−0·03 points [4·04]; −0·94 to 0·88; between-group difference Cohen's d 0·58; p=0·0004). Eight patients had adverse events during therapy or treatment deferral (one car accident [in the control group], two common cold [one patient per group], three gastrointestinal or cardiac symptoms [all intervention group], two recurrent stroke [one in intervention group before initiation of treatment, and one before group assignment had occurred]); all were unrelated to study participation. Interpretation 3 weeks of intensive speech and language therapy significantly enhanced verbal communication in people aged 70 years or younger with chronic aphasia after stroke, providing an effective evidence-based treatment approach in this population. Future studies should examine the minimum treatment intensity required for meaningful treatment effects, and determine whether treatment effects cumulate over repeated intervention periods. Funding German Federal Ministry of Education and Research and the German Society for Aphasia Research and Treatment.

Background To increase the removal of middle-sized uremic toxins a new membrane with enhanced permeability and selectivity, called Medium Cut-Off membrane (MCO-Ci) has been developed that at the same time ensures the retention of albumin. Because many middle-sized substances may contribute to micro-inflammation we hypothesized that the use of MCO-Ci influences the inflammatory state in hemodialysis patients. Methods The randomized crossover trial in 48 patients compared MCO-Ci dialysis to High-flux dialysis of 4 weeks duration each plus 8 weeks extension phase. Primary endpoint was the gene expression of TNF-α and IL-6 in peripheral blood mononuclear cells (PBMCs), secondary endpoints were plasma levels of specified inflammatory mediators and cytokines. Results After four weeks of MCO-Ci the expression of TNF-α mRNA (Relative quantification (RQ) from 0.92 ± 0.34 to 0.75 ± 0.31, -18.5%, p

Effective drug selection is the current challenge in rheumatoid arthritis (RA). Treatment failure may follow different pathomechanisms and therefore require investigation of molecularly defined subgroups. In this exploratory study, whole blood transcriptomes of 68 treatment-naive early RA patients were analyzed before initiating MTX. Subgroups were defined by serologic and genetic markers. Response related signatures were interpreted using reference transcriptomes of various cell types, cytokine stimulated conditions and bone marrow precursors. HLA-DRB4-negative patients exhibited most distinctive transcriptional differences. Preponderance of transcripts associated with phagocytes and bone marrow activation indicated response and transcripts of T- and B-lymphocytes non-response. HLA-DRB4-positive patients were more heterogeneous, but also linked failure to increased adaptive immune response. RT-qPCR confirmed reliable candidate selection and independent samples of responders and non-responders the functional patterning. In summary, genomic stratification identified different molecular pathomechanisms in early RA and preponderance of innate but not adaptive immune activation suggested response to MTX therapy.

Introduction The approved analgesic and anti-inflammatory drugs ibuprofen and indometacin block the small GTPase RhoA, a key enzyme that impedes axonal sprouting after axonal damage. Inhibition of the Rho pathway in a central nervous system-effective manner requires higher dosages compared with orthodox cyclooxygenase-blocking effects. Preclinical studies on spinal cord injury (SCI) imply improved motor recovery after ibuprofen/indometacin-mediated Rho inhibition. This has been reassessed by a meta-analysis of the underlying experimental evidence, which indicates an overall effect size of 20.2% regarding motor outcome achieved after ibuprofen/indometacin treatment compared with vehicle controls. In addition, ibuprofen/indometacin may also limit sickness behaviour, non-neurogenic systemic inflammatory response syndrome (SIRS), neuropathic pain and heterotopic ossifications after SCI. Consequently, ‘small molecule’-mediated Rho inhibition after acute SCI warrants clinical investigation. Methods and analysis Protocol of an investigator-initiated clinical open-label pilot trial on high-dose ibuprofen treatment after acute traumatic, motor-complete SCI. A sample of n=12 patients will be enrolled in two cohorts treated with 2400 mg/day ibuprofen for 4 or 12 weeks, respectively. The primary safety end point is an occurrence of serious adverse events, primarily gastroduodenal bleedings. Secondary end points are pharmacokinetics, feasibility and preliminary effects on neurological recovery, neuropathic pain and heterotopic ossifications. The primary safety analysis is based on the incidence of severe gastrointestinal bleedings. Additional analyses will be mainly descriptive and casuistic. Ethics and dissemination The clinical trial protocol was approved by the responsible German state Ethics Board, and the Federal Institute for Drugs and Medical Devices. The study complies with the Declaration of Helsinki, the principles of Good Clinical Practice and all further applicable regulations. This safety and pharmacokinetics trial informs the planning of a subsequent randomised controlled trial. Regardless of the result of the primary and secondary outcome assessments, the clinical trial will be reported as a publication in a peer-reviewed journal. Trial registration number NCT02096913; Pre-results.

Purpose Degenerative retinal diseases, especially retinitis pigmentosa (RP), lead to severe peripheral visual field loss (tunnel vision), which impairs mobility. The lack of peripheral information leads to fewer horizontal eye movements and, thus, diminished scanning in RP patients in a natural environment walking task. This randomized controlled study aimed to improve mobility and the dynamic visual field by applying a compensatory Exploratory Saccadic Training (EST). Methods Oculomotor responses during walking and avoiding obstacles in a controlled environment were studied before and after saccade or reading training in 25 RP patients. Eye movements were recorded using a mobile infrared eye tracker (Tobii glasses) that measured a range of spatial and temporal variables. Patients were randomly assigned to two training conditions: Saccade (experimental) and reading (control) training. All subjects who first performed reading training underwent experimental training later (waiting list control group). To assess the effect of training on subjects, we measured performance in the training task and the following outcome variables related to daily life: Response Time (RT) during exploratory saccade training, Percent Preferred Walking Speed (PPWS), the number of collisions with obstacles, eye position variability, fixation duration, and the total number of fixations including the ones in the subjects' blind area of the visual field. Results In the saccade training group, RTs on average decreased, while the PPWS significantly increased. The improvement persisted, as tested 6 weeks after the end of the training. On average, the eye movement range of RP patients before and after training was similar to that of healthy observers. In both, the experimental and reading training groups, we found many fixations outside the subjects' seeing visual field before and after training. The average fixation duration was significantly shorter after the training, but only in the experimental training condition. Conclusions We conclude that the exploratory saccade training was beneficial for RP patients and resulted in shorter fixation durations after the training. We also found a significant improvement in relative walking speed during navigation in a real-world like controlled environment.

Patients with chronic kidney disease maintained on intermittent hemodialysis suffer from systemic chronic inflammation which is causally associated with high mortality. Inflammation mediators of 15-45 kDa range cannot be effectively removed by conventional dialysis membranes. In this study, we tested the influence of serum and dialysates obtained from patients maintained on High cut-off or High flux membranes on the inflammation profile of THP-1 monocytes.THP-1 monocytes were treated with serum or dialysates obtained from patients maintained on High cut-off and High flux membranes within a randomized crossover pilot trial. Serum-treated cells were subjected to qPCR analyses with TaqMan probes specific for IL6, TNFa, osteopontin and osteocalcin, and transcriptional screening with Inflammatory Array. Apoptosis assay was performed flow cytometrically with 7-AAD and Annexin V staining.Treatment of the cells with High cut-off serum led to significant reduction of TNFa and IL-6 expression as well as inflammation-related osteopontin and osteocalcin as compared to High flux membrane treatment. As a complementary finding, treatment with High cut-off dialysates induced a pro-apoptotic phenotype in the cells as demonstrated by a significantly increased percentage of 7-AAD and Annexin V positivity. Global screening of serum-treated cells revealed noticeably decreased inflammation profile under High cut-off serum as compared to High flux treatment.Taken together, these data demonstrate that High cut-off -membranes eliminate a spectrum of mediators from serum into the dialysate that possess proinflammatory properties and may impair cellular viability.

Background and Purpose— A patent foramen ovale (PFO) is disproportionately prevalent in patients with cryptogenic stroke. Without alternative explanations, it is frequently considered to be causative. A detailed stratification of these patients may improve the identification of incidental PFO. Methods— We investigated the PFO prevalence in 3497 transient ischemic attack and ischemic stroke patients aged 18 to 55 years in the prospective multicenter SIFAP1 study (Stroke in Young Fabry Patients 1) using the ASCO classification. Patients without an obvious cause for transient ischemic attack/stroke (ASCO 0) were divided into subgroups with and without vascular risk factors (ASCO 0+ and 0−). In addition, we looked for PFO-related magnetic resonance imaging lesion patterns. Results— PFO was identified in 25% of patients. Twenty percent of patients with a definite or probable cause of transient ischemic attack/stroke (≥1 grade 1 or 2 ASCO criterion; n=1769) had a PFO compared with 29% of cryptogenic stroke patients (ASCO 0 and 3; n=1728; P P P Conclusions— Cryptogenic stroke patients demonstrate a heterogeneous PFO prevalence. Even in case of less conclusive diseases like nonstenotic arteriosclerosis, patients should preferentially be considered to have a non-PFO-mediated stroke. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00414583.

Objective To determine whether kidney transplants performed during a weekend had worse outcomes than those performed during weekdays. Design Retrospective national database study. Setting United Network for Organ Sharing database of the USA. Participants 136 715 adult recipients of deceased donor single organ kidney transplants in the USA between 4/1994 and 9/2010. Main outcome measures The primary outcomes were patient survival and death-censored and overall allograft survival. Secondary outcomes included initial length of hospital stay after transplantation, delayed allograft function, acute rejection within the first year of transplant, and patient and allograft survival at 1 month and at 1 year after transplantation. Cox proportional hazards models were used to evaluate the impact of weekend kidney transplant surgery on primary and secondary outcomes, adjusting for multiple covariates. Results Among the 136 715 kidney recipients, 72.5% underwent transplantation during a regular weekday (Monday–Friday) and 27.5% during a weekend (Saturday–Sunday). No significant association was noted between weekend transplant status and patient survival, death-censored allograft survival or overall allograft survival in the adjusted analyses (HR 1.01 (95% CI 0.92 to 1.04), 1.012 (95% CI 0.99 to 1.034), 1.012 (95% CI 0.984 to 1.04), respectively). In addition, no significant association was noted between weekend transplant status and the secondary outcomes of patient and graft survival at 1 month and 1 year, delayed allograft function or acute rejection within the first year. Results remained consistent across all definitions of weekend status. Conclusions The outcomes for deceased donor kidney transplantation in the USA are not affected by the day of surgery. The operationalisation of deceased donor kidney transplantation may provide a model for other surgeries or emergency procedures that occur over the weekend, and may help reduce length of hospital stay and improve outcomes.

Purpose In this phase II study (NCT00942747), temsirolimus was tested in patients with relapsed or refractory primary CNS lymphoma (PCNSL). Patients and Methods Immunocompetent adults with histologically confirmed PCNSL after experiencing high-dose methotrexate-based chemotherapy failure who were not eligible for or had experienced high-dose chemotherapy with autologous stem-cell transplant failure were included. The first cohort (n = 6) received 25 mg temsirolimus intravenously once per week. All consecutive patients received 75 mg intravenously once per week. Results Thirty-seven eligible patients (median age, 70 years) were included whose median time since their last treatment was 3.9 months (range, 0.1 to 14.6 months). Complete response was seen in five patients (13.5%), complete response unconfirmed in three (8%), and partial response in 12 (32.4%) for an overall response rate of 54%. Median progression-free survival was 2.1 months (95% CI, 1.1 to 3.0 months). The most frequent Common Toxicity Criteria ≥ 3° adverse event was hyperglycemia in 11 (29.7%) patients, thrombocytopenia in eight (21.6%), infection in seven (19%), anemia in four (10.8%), and rash in three (8.1%). Fourteen blood/CSF pairs were collected in nine patients (10 pairs in five patients in the 25-mg cohort and four pairs in four patients in the 75-mg cohort). The mean maximum blood concentration was 292 ng/mL for temsirolimus and 37.2 ng/mL for its metabolite sirolimus in the 25-mg cohort and 484 ng/mL and 91.1 ng/mL, respectively, in the 75-mg cohort. Temsirolimus CSF concentration was 2 ng/mL in one patient in the 75-mg cohort; in all others, no drug was found in their CSF. Conclusion Single-agent temsirolimus at a weekly dose of 75 mg was found to be active in relapsed/refractory patients with PCNSL; however, responses were usually short lived.

The PREFERE study, which compares the treatment options for prostate cancer with low and early intermediate risk, has recorded a noticeable upswing in recruitment since mid-2015. Responsible for this are the revised inclusion criteria and the wide support for this study in Germany. The inclusion criteria opened the study to the use of imaging techniques (MRI, C‑Trus / Anna) and the inclusion of all Gleason 3 + 3 = 6 cancers, regardless of tumor extent. In addition, patients can now be included who, for example due to the size of the prostate or existing obstructive micturition disorders, had a contraindication to percutaneous radiotherapy or brachytherapy - these can now be randomized between active surveillance and radical prostatectomy. With the increased recruitment numbers, it seems realistic that the required milestones in recruiting will be achieved.

Central nervous system lymphoma (CNSL) is diagnostically challenging. The identification of reliable and easy to measure biomarkers is desirable to facilitate diagnosis. Here, we evaluated the value of cerebrospinal fluid (CSF) osteopontin (OPN) as a diagnostic biomarker for CNSL. OPN concentrations in CSF from 37 patients with CNSL (29 with primary CNSL and 8 with secondary CNS involvement of systemic lymphoma) and 36 controls [6 patients with inflammatory CNS disease other than multiple sclerosis (MS), 8 with MS, 9 with glioblastoma (GBM) and 13 healthy controls] were determined using an enzyme-linked immunosorbent assay. Non-parametric tests and receiver operating characteristic (ROC) curves were performed for determination of diagnostic accuracy. Median CSF OPN level in all CNSL patients was 620 ng/mL and higher than in patients with inflammatory CNS disease (356 ng/mL); P

Purpose: Facing the lack of time, busy retina consultants should be aware of how the patients would prefer that time is spent and whether they wish the specialist to talk more at the expense of other medical activities. Methods: 810 persons with diabetes were asked to divide the time of 10 min between examination, consultation and treatment when envisioning a real-life scenario of diabetic retinopathy (NCT02311504). Results: With the increasing duration of diabetes, patients wanted significantly more time for diagnostics (p = 0.028), while age was found to be associated with less time for treatment (p = 0.009). Female subjects tended to prefer only little more time for talking (p = 0.051) in comparison with males, who slightly favored therapy (p = 0.025). Conclusions: The large majority recognized the need for diagnostics in their allocation of time. If individual patients are confronted with the health care perspective of time constraints, this might improve the understanding of prioritization.

Spreading depolarizations (SD) are waves of abrupt, near-complete breakdown of neuronal transmembrane ion gradients, are the largest possible pathophysiologic disruption of viable cerebral gray matter, and are a crucial mechanism of lesion development. Spreading depolarizations are increasingly recorded during multimodal neuromonitoring in neurocritical care as a causal biomarker providing a diagnostic summary measure of metabolic failure and excitotoxic injury. Focal ischemia causes spreading depolarization within minutes. Further spreading depolarizations arise for hours to days due to energy supply-demand mismatch in viable tissue. Spreading depolarizations exacerbate neuronal injury through prolonged ionic breakdown and spreading depolarization-related hypoperfusion (spreading ischemia). Local duration of the depolarization indicates local tissue energy status and risk of injury. Regional electrocorticographic monitoring affords even remote detection of injury because spreading depolarizations propagate widely from ischemic or metabolically stressed zones; characteristic patterns, including temporal clusters of spreading depolarizations and persistent depression of spontaneous cortical activity, can be recognized and quantified. Here, we describe the experimental basis for interpreting these patterns and illustrate their translation to human disease. We further provide consensus recommendations for electrocorticographic methods to record, classify, and score spreading depolarizations and associated spreading depressions. These methods offer distinct advantages over other neuromonitoring modalities and allow for future refinement through less invasive and more automated approaches.

Purpose: To investigate changes of peripheral blood biomarkers and their impact on clinical outcome following treatment with ipilimumab in advanced melanoma patients. Experimental Design: Changes in blood counts and the frequency of circulating immune cell populations analyzed by flow cytometry were investigated in 82 patients to compare baseline values with different time-points after starting ipilimumab. Endpoints were overall survival (OS) and best clinical response. Statistical calculations were done by Wilcoxon-matched pairs tests, Fisher exact test, Kaplan–Meier analysis, and Cox regression analysis. Results: Increases in absolute lymphocyte counts (ALC) 2 to 8 weeks (P = 0.003) and in percentages of CD4+ and CD8+ T cells 8 to 14 weeks (P = 0.001 and P = 0.02) after the first dose of ipilimumab were correlated with improved survival. These associations did not meet significance criteria, when conservatively adjusted for multiple testing, but were additionally correlated with clinical responses (all P < 0.05). However, validation is required. Increases in all three factors were observed in 36% of patients, who had a favorable outcome and survival probabilities of 93.3% and 63.8% at 12 and 24 months, respectively. A partial or complete response was observed in 71% of these patients compared with only 8% in patients with decreases in ≥1 of the 3 factors, respectively. Changes of regulatory T cells or myeloid-derived suppressor cells were not associated with OS. Conclusions: Increases of ALC observed 2 to 8 weeks after initiation of ipilimumab and delayed increases in CD4+ and CD8+ T cells reflect changes associated with positive outcome. These changes represent surrogate marker candidates and warrant further validation. Clin Cancer Res; 22(19); 4848–58. ©2016 AACR.

Body image disturbance represents a central characteristic of anorexia nervosa (AN). Depression and anxiety are the most common mental comorbidities in patients with AN. This study aims to investigate the relationship of body image with symptoms of depression and anxiety during outpatient psychotherapy in AN. Analyses were conducted using the data set of the Anorexia Nervosa Treatment Outpatient Study (ANTOP) randomized controlled trial. The ANTOP study included N = 242 females with AN between 18 and 56 years of age. The trial was designed to compare enhanced cognitive behavioral therapy (CBT-E) and focal psychodynamic therapy (FPT) with optimized treatment as usual (TAU-O) for patients with AN. The analyses on body image dimensions were conducted using measures of correlations and multiple linear regression analyses to assess the relationship and longitudinal prediction of symptoms of depression and anxiety by body image dimensions. Results showed that body image perceptions were significantly associated with symptoms of depression and anxiety in patients with AN at all treatment stages. In addition, body image dimensions at early treatment stages predict depression and anxiety in follow-up measurements. The correlation of symptoms of depression and anxiety by body image perceptions increased along treatment course. The persistence of body image disturbance, while body mass index increases under treatment (persistency effect), may constitute a relevant factor contributing to the course of the most common affective comorbidities of depression and anxiety in patients with AN. Body image disturbances in patients with AN should therefore be explicitly targeted within the specialized psychotherapy of affected patients. (PsycINFO Database Record

Background Public health monitoring depends on valid health and disability estimates in the population 65+ years. This is hampered by high non- participation rates in this age group. There is limited insight into size and direction of potential baseline selection bias. Methods We analyzed baseline non-participation in a register-based random sample of 1481 inner-city residents 65+ years, invited to a health examination survey according to demographics available for the entire sample, self-report information as available and reasons for non-participation. One year after recruitment, non- responders were revisited to assess their reasons. Results Five groups defined by participation status were differentiated: participants (N = 299), persons who had died or moved (N = 173), those who declined participation, but answered a short questionnaire (N = 384), those who declined participation and the short questionnaire (N = 324), and non-responders (N = 301). The results confirm substantial baseline selection bias with significant underrepresentation of persons 85+ years, persons in residential care or from disadvantaged neighborhoods, with lower education, foreign citizenship, or lower health-related quality of life. Finally, reasons for non-participation could be identified for 78 % of all non-participants, including 183 non- responders. Conclusion A diversity in health problems and barriers to participation exists among non-participants. Innovative study designs are needed for public health monitoring in aging populations.

Purpose: To identify baseline peripheral blood biomarkers associated with clinical outcome following ipilimumab treatment in advanced melanoma patients. Experimental Design: Frequencies of myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg), serum lactate dehydrogenase (LDH), routine blood counts, and clinical characteristics were assessed in 209 patients. Endpoints were overall survival (OS) and best overall response. Statistical calculations were done by Kaplan–Meier and Cox regression analysis, including calibration and discrimination by C-statistics. Results: Low baseline LDH, absolute monocyte counts (AMC), Lin−CD14+HLA-DR−/low-MDSC frequencies, and high absolute eosinophil counts (AEC), relative lymphocyte counts (RLC), and CD4+CD25+FoxP3+-Treg frequencies were significantly associated with better survival, and were considered in a combination model. Patients (43.5%) presenting with the best biomarker signature had a 30% response rate and median survival of 16 months. In contrast, patients with the worst biomarkers (27.5%) had only a 3% response rate and median survival of 4 months. The occurrence of adverse events correlated with neither baseline biomarker signatures nor the clinical benefit of ipilimumab. In another model, limited to the routine parameters LDH, AMC, AEC, and RLC, the number of favorable factors (4 vs. 3 vs. 2–0) was also associated with OS (P < 0.001 for all pairwise comparisons) in the main study and additionally in an independent validation cohort. Conclusions: A baseline signature of low LDH, AMC, and MDSCs as well as high AEC, Tregs, and RLC is associated with favorable outcome following ipilimumab. Prospective investigation of the predictive impact of these markers following ipilimumab and other treatments, e.g., PD-1 antibodies, is warranted. Clin Cancer Res; 22(12); 2908–18. ©2016 AACR.

The prognosis of patients with central nervous system relapse of aggressive lymphoma is very poor with no therapy established so far. In a prospective multicenter phase II study, we evaluated a potentially curative chemotherapy-only regimen in these patients. Adult immunocompetent patients 65 years of age or under received induction chemotherapy with MTX/IFO/DEP (methotrexate 4 g/m(2) intravenously (i.v.) Day 1, ifosfamide 2 g/m(2) i.v. Days 3- 5 and liposomal cytarabine 50 mg intrathecally (i.th) Day 6) and AraC/TT/DEP (cytarabine 3g/m(2) i.v. Days 1-2, thiotepa 40 mg/m(2) i.v. Day 2 and i.th. liposomal cytarabine 50 mg i.th. Day 3) followed by high-dose chemotherapy with carmustine 400 mg/m(2) i.v. Day -5, thiotepa 2×5 mg/kg i.v. Days -4 to -3 and etoposide 150 mg/m(2) i.v. Days -5 to -3, and autologous stem cell transplantation Day 0 (HD-ASCT). Thirty eligible patients (median age 58 years) were enrolled. After HD-ASCT (n=24), there was a complete remission in 15 (63%), partial remission in 2 (8%) and progressive disease in 7 (29%) patients. Myelotoxicity was the most adverse event with CTC grade 3/4 infections in 12% of MTX/IFO/DEP courses, 21% of AraC/TT/DEP courses and 46% of HD-ASCT courses. The 2-year time to treatment failure was 49%±19 for all patients and 58%±22 for patients completing HD-ASCT. The protocol assessed proved feasible and highly active with long-lasting remissions in a large proportion of patients. (ClinicalTrials.govIdentifier NCT01148173).

The standard of care for primary central nervous system lymphoma (PCNSL) is systemic chemotherapy with or without whole brain radiotherapy or intrathecal chemotherapy. In contrast to treatment for other brain tumors, efforts at resection are discouraged. This is a secondary analysis of the German PCNSL Study Group-1 trial, a large randomized phase III study comprising 526 patients with PCNSL. Progression-free survival (hazard ratio [HR]: 1.39; 95% confidence interval [CI]: 1.10-1.74; P = .005) and overall survival (HR: 1.33; 95% CI: 1.04-1.70; P = .024) were significantly shorter in biopsied patients compared with patients with subtotal or gross total resections. This difference in outcome was not due to age or Karnofsky performance status (KPS). When controlled for the number of lesions, the HR of biopsy versus subtotal or gross total resection remained unchanged for progression-free survival (HR = 1.37; P = .009) but was smaller for overall survival (HR = 1.27; P = .085). This analysis of the largest PCNSL trial ever performed challenges the traditional view that the extent of resection has no prognostic impact on this disease. Therefore, we propose to reconsider the statement that efforts at resection should be discouraged, at least if resection seems safe, as is often the case in treatment of single PCNSL lesions.

Background Recurrent angioedema is a frequent clinical problem characterized by unpredictably and rapidly occurring cutaneous and mucosal swellings. These swellings may be painful and/or disfiguring. Upper airway involvement can also lead to dyspnea and suffocation. Although the disease burden is high, there is currently no specific instrument to measure health-related quality of life (QoL) impairment. Objective To develop and validate the first symptom-specific tool to assess QoL impairment in recurrent angioedema patients, adhering to established methodological recommendations. Methods During the development phase, 29 questions (items) were generated. Subsequently, item reduction was performed by means of impact analysis and factor analysis as well as by checking for content and face validity. As a result, 17 items were selected and included in the final instrument, the Angioedema QoL Questionnaire (AE-QoL). AE-QoL was then tested for its validity, reliability, and influence factors. Results One hundred and ten angioedema patients took part in the validation of AE-QoL. AE-QoL was found to have a four-dimensional structure as well as a valid total score. All of its four domains (functioning, fatigue/mood, fears/shame, food) showed good levels of internal consistency with Cronbach's alpha > 0.8. Test–retesting revealed a good reliability of the instruments total score and domain scores. Gender as well as the patients' self-rated disease activity was found to be predictors of the AE-QoL total score. Conclusions Angioedema Quality of Life Questionnaire is the first angioedema-specific QoL questionnaire. It is a short, valid and reliable instrument that may serve as a valuable tool in future clinical studies and in routine patient care.

Background The well-being of patients with Parkinson’s disease may be improved by pharmaceutical care in community pharmacies. Objective To investigate the effects of standardised pharmaceutical care on health outcomes and quality of drug treatment in patients with Parkinson’s disease. Setting Community pharmacies in Germany. Method An open-label, multicentre, longitudinal, parallel-group study was conducted in outpatients with idiopathic Parkinson’s disease who were receiving anti-parkinsonian medication. Patients were recruited by 32 community pharmacists (pharmacy group) and local offices of the German Parkinson’s disease patients’ association (comparison group). All patients were assessed at baseline and at 8 months’ follow-up. In the intervening period, the pharmacists provided patients in the pharmacy group with standardised pharmaceutical care. Main outcome measure Mean change in symptom-related impairment of health status, assessed using the 23-item Parkinson’s Scale Total Score. Results In total 235 patients were enrolled into the study (113 pharmacy group; 122 comparison group). Between-group analysis showed that the mean changes in the primary and secondary endpoints, all 23-item Parkinson’s Scale sub-scores and the EuroQol 5-Dimension Questionnaire Index Score were significantly in favour of the pharmacy group after 8 months (p < 0.05 to p < 0.001), using a mixed model analysis. No significant changes were observed in prescribers’ guideline adherence, but there was a significant decrease in the proportion of patients receiving inappropriate drugs according to the Beers List in the pharmacy group (p < 0.01). Conclusion This study shows that significant benefits in patient health outcomes and age-related quality of drug treatment were gained when patients with Parkinson’s disease were provided with standardised pharmaceutical care in community pharmacies.

To provide evidence for the validity of the Fragebogen zur Lebensqualitat multimorbider alterer Menschen (FLQM; English: Quality of life in elders with multimorbidity), a new tool for the assessment of life-satisfaction as a subjective indicator of quality of life in old age. The FLQM measures overall life-satisfaction based on those self-generated domains in life that are most important to the respondent. Construct validity (correlations with convergent and divergent scales) and differential validity (subgroup differences with respect to age and limitations in everyday functioning) were analyzed in an urban sample of older adults (n = 299; 54.6% male; Mean (age) = 75.65 years, SD = 6.57). Correlations of FLQM with measures of similar constructs were close (r = 0.35–0.50; p

BACKGROUND.: Dialysis bath production, at least in Europe, is currently based on pre-produced aqueous solutions of dialysis salts (concentrate), which are re-handled by dialysis machines to deliver the final dialysate concentrations. Because of the logistics of aqueous solution creation, a large amount of transportation capacity is needed. Therefore, we changed this process to use pre-produced dry salt containers and to undertake in-clinic dissolution of salts and concentration production. Because no preclinical control for solute concentrations is available so far using this new process, we employed routine clinical chemistry analytics. METHODS.: We report the controls of solute concentrations created by these methods for 746 samples of concentrates and 151 dissolution processes. For analysis, absolute and relative deviations from prescriptions and associations between the solute concentrations and the density controls of the concentrates were computed. RESULTS.: A total of 98% of all the concentrates were found to be within a 10% margin of error from the prescriptions. The mean relative deviation of the solute concentrations from the prescriptions was -0.635 ± 3.83%. Among particular solutes, sodium had the highest maximum deviation of 26 mmol/L from the prescription. Calcium and magnesium (small concentration solutes) exhibited small systematic errors of 1.37 and 1.22%, respectively. Other solute concentrations showed random errors only and no associations with the mean relative deviations of all the solutes within a production batch or with the density controls. CONCLUSIONS.: Single solute concentration control by routine clinical chemistry after dry salt production of concentrates is a valuable additional tool for monitoring clinical risk with dialysate concentrates. The analytical random error of clinical chemistry exceeds the weight tolerance of production; therefore, such analytics cannot be used for precision production and control of dry salt containers.

Spreading depolarization of cells in cerebral grey matter is characterized by massive ion translocation, neuronal swelling and large changes in direct current-coupled voltage recording. The near-complete sustained depolarization above the inactivation threshold for action potential generating channels initiates spreading depression of brain activity. In contrast, epileptic seizures show modest ion translocation and sustained depolarization below the inactivation threshold for action potential generating channels. Such modest sustained depolarization allows synchronous, highly frequent neuronal firing; ictal epileptic field potentials being its electrocorticographic and epileptic seizure its clinical correlate. Nevertheless, Leao in 1944 and Van Harreveld and Stamm in 1953 described in animals that silencing of brain activity induced by spreading depolarization changed during minimal electrical stimulations. Eventually, epileptic field potentials were recorded during the period that had originally seen spreading depression of activity. Such spreading convulsions are characterized by epileptic field potentials on the final shoulder of the large slow potential change of spreading depolarization. We here report on such spreading convulsions in monopolar subdural recordings in 2 of 25 consecutive aneurismal subarachnoid haemorrhage patients in vivo and neocortical slices from 12 patients with intractable temporal lobe epilepsy in vitro . The in vitro results suggest that γ-aminobutyric acid-mediated inhibition protects from spreading convulsions. Moreover, we describe arterial pulse artefacts mimicking epileptic field potentials in three patients with subarachnoid haemorrhage that ride on the slow potential peak. Twenty-one of the 25 subarachnoid haemorrhage patients (84%) had 656 spreading depolarizations in contrast to only three patients (12%) with 55 ictal epileptic events isolated from spreading depolarizations. Spreading depolarization frequency and depression periods per 24 h recording episodes showed an early and a delayed peak on Day 7. Patients surviving subarachnoid haemorrhage with poor outcome at 6 months showed significantly higher total and peak numbers of spreading depolarizations and significantly longer total and peak depression periods during the electrocorticographic monitoring than patients with good outcome. In a semi-structured telephone interview 3 years after the initial haemorrhage, 44% of the subarachnoid haemorrhage survivors had developed late post-haemorrhagic seizures requiring anti-convulsant medication. In those patients, peak spreading depolarization number had been significantly higher [15.1 (11.4–30.8) versus 7.0 (0.8–11.2) events per day, P = 0.045]. In summary, monopolar recordings here provided unequivocal evidence of spreading convulsions in patients. Hence, practically all major pathological cortical network events in animals have now been observed in people. Early spreading depolarizations may indicate a risk for late post-haemorrhagic seizures. * Abbreviations : GABA : γ-aminobutyric acid SAH : subarachnoid haemorrhage

NSO heterocycles (HET) are typical constituents of coal tars. However, HET are not yet routinely monitored, although HET are relatively toxic coal tar constituents. The main objectives of the study is therefore to review previous studies and to analyse HET at coal tar polluted sites in order to assess the relevance of HET as part of monitored natural attenuation (MNA) or any other long-term monitoring programme. Hence, natural attenuation of typical HET (indole, quinoline, carbazole, acridine, methylquinolines, thiophene, benzothiophene, dibenzothiophene, benzofuran, dibenzofuran, methylbenzofurans, dimethylbenzofurans and xanthene) were studied at three different field sites in Germany. Compound-specific plume lengths were determined for all main contaminant groups (BTEX, PAH and HET). The results show that the observed plume lengths are site-specific and are above 250 m, but less than 1000 m. The latter, i.e. the upper limit, however mainly depends on the level of investigation, the considered compound, the lowest measured concentration and/or the achieved compound-specific detection limit and therefore cannot be unequivocally defined. All downstream contaminant plumes exhibited HET concentrations above typical PAH concentrations indicating that some HET are generally persistent towards biodegradation compared to other coal tar constituents, which results in comparatively increased field-derived half-lives of HET. Additionally, this study provides a review on physicochemical and toxicological parameters of HET. For three well investigated sites in Germany, the biodegradation of HET is quantified using the centre line method (CLM) for the evaluation of bulk attenuation rate constants. The results of the present and previous studies suggest that implementation of a comprehensive monitoring programme for heterocyclic aromatic compounds is relevant at sites, if MNA is considered in risk assessment and for remediation.

Summary Background: Skin care is important especially in infancy as the skin barrier matures during the first year of life. We studied the effects of baby swimming and baby lotion on the skin barrier function of infants. Subjects and methods: 44 infants aged 3–6 months were included in this mono-center prospective study. The healthy infants swam four times and were randomized to groupL: baby lotion was applied after swimming all over the body and to groupWL: no lotion was used. Transepidermal water loss, stratum corneum hydration, skin-pH and sebum were measured on four body regions using non-invasive methods. Results: In groupL, sebum and pH remained stable. In groupWL, significant decrease in sebum was noted on forehead and thigh, and for pH on thigh and buttock. GroupL had fewer infants with at least one adverse event compared to groupWL. Location-dependent gender differences in skin barrier function were observed. Conclusions: Reaction of skin barrier function to baby swimming and skin care regimens showed typical regional variability between body areas. Influence of baby lotion on skin barrier and gender differences in skin functional parameters were demonstrated for the first time in healthy infants participating in baby swimming.

Functional characteristics of tuberculosis (TB)-specific CD4 T cells were studied in clinically active pulmonary TB (n = 21) and high TB exposure including LTBI (n = 17). Following tuberculin stimulation, activated CD4 T cells were identified by flow-cytometry (CD154 up-regulation, degranulation, interferon γ [IFN-γ], tumor necrosis factor α [TNF-α], and interleukin 2 [IL-2\ production). Interestingly, CD154 up-regulation accounted for ∼80% of activated CD4 T cells in the active TB group but just 40% in the controls, whereas IFN-γ accounted for only ∼50% of activated cells in each group. The frequencies of CD4 T cells displaying at least 1 activation marker discriminated better between the groups than those displaying degranulation or IFN-γ production alone.

Aim: This study aims to analyse the association between ethnicity, elevated metabolic parameters and metabolic syndrome (MS) in a multiethnic cohort of overweight to obese children and adolescents. Methods: For 1053 patients, standard deviation of body mass index (BMI-SDS) was calculated and metabolic parameters (fasting blood glucose, fasting insulin, homeostasis model assessment-IR, lipids, blood pressure) were measured. MS was defined by WHO criteria. Bivariate and multivariate analyses were performed. Adjusted differences in BMI-SDS and metabolic parameters between different migration groups were assessed with linear regression models. The risk for MS was calculated with multiple logistic regression models. Results: Forty-eight per cent of the children were German, 25% Turkish and 27% had another ethnicity. Concerning weight status, 23% are overweight, 31% obese and 46% extremely obese with higher rates among the immigrant population. Multivariable models indicate significant associations between elevated metabolic parameters and higher BMI-SDS values. Overall prevalence of MS was 32.3%. MS was detected significantly more often among Turkish patients (40.4%) compared to Germans (27.3%; p = 0.02). Logistic regression analysis showed a greater risk for MS with older age (OR = 1.09; p = 0.003) and Turkish ethnicity (OR = 1.62; p = 0.02). Conclusion: Nearly all patients had symptoms of MS, and 40% had MS showing that this highly health-threatening condition is quite common. Therefore, effective therapy and prevention efforts must be developed for this high risk group. More migration-specific research regarding insulin resistance, MS and Type 2 DM is needed.

Background: Moyamoya disease (MMD) is graded based on digital subtraction angiography (DSA) with limited clinical applications. The aim was to identify clinically relevant parameters that may be used to develop a novel MMD grading system. Methods: In 40 MMD patients bilateral revascularization surgery was performed. Clinical data including DSA, MRI and regional cerebral blood flow studies were assessed. χ2 test corrected for dependency of measurements at the same subject and analysis of receiver operating characteristics were used to identify key parameters. Grading system included: DSA (stenosis/occlusion = 1 point; stenosis/occlusion + intracranial compensation = 2 points; stenosis/occlusion + intracranial compensation + extra-intracranial compensation = 3 points), MRI (no sign of ischemia = 0 points; signs of ischemia = 1 point) and cerebrovascular reserve capacity (CVRC > –5% = 0 points; CVRC < –5% = 2 points). MMD grade I referred to 1–2 points, grade II to 3–4 and grade III to 5–6 points. Results: DSA, MRI and CVRC were dependent factors associated with the occurrence of clinical symptoms. Receiver operating characteristics analysis indentified the grading system as superior to each single parameter in predicting clinical symptoms. Fourteen hemispheres were graded as mild (grade I), 35 as moderate (grade II) and 31 as severe (grade III); 21% of grade I, 63% of grade II and 93% of grade III hemispheres were clinically symptomatic. Conclusions: The proposed grading system allows to stratify for clinical symptomatology in MMD patients. Future studies will have to investigate its value for assessing clinical symptoms and treatment risks.

Background: Fabry disease (FD) is a rare hereditary lysosomal storage disease that has been highlighted as a possible etiology of stroke at a young age. Enlarged basilar artery diameters (BADs) have been demonstrated in FD, and we hypothesize that they might be useful for the screening of FD in young stroke patients. The aim of this study was to compare BADs of young stroke patients without FD to those of FD patients and of healthy age-matched controls. Methods: BADs were measured using MR angiography in 3 age- and gender-matched groups: 25 FD patients (aged 36.5 ± 11.0 years), 26 non-FD stroke patients and 20 healthy controls. Results: Compared to the non-FD stroke patients, FD patients had significantly enlarged BADs. FD patients could be significantly separated from stroke patients by BADs (area under the curve = 0.89, 95% confidence interval 0.81–0.98). Eighty-six percent of all subjects could be correctly classified by BADs (sensitivity 84%, specificity 88.5%). Conclusions: Enlarged BADs were able to detect FD within a cohort of FD, stroke patients and healthy controls. BAD measurement could be an easily obtainable and sensitive screening tool for FD in young stroke patients.

The scientific evidence for weather being a trigger factor for migraine attacks is inconclusive. We investigated the association between weather components and the onset and severity of attacks. Headache diaries of 20 migraineurs were analyzed retrospectively and correlated in 4-h intervals to atmospheric air pressure, temperature, and relative air humidity in Berlin (Germany) for a period of 12 consecutive months. Absolute values and relative changes within the preceding 24 h were analyzed. Migraine attacks started most frequently at 4 a.m. and reached the highest intensity between 4 and 8 a.m. A highly significant association between meteorological variables and the occurrence of migraine attacks was found in six patients. The onset of an attack as well as high headache intensity was associated with lower temperature and higher humidity. Our data indicate that a subgroup of migraineurs is highly sensitive to changes of certain weather components.

ObjectiveTo study whether metformin reduces obesity, homeostasis model assessment for insulin resistance index (HOMA-IR), and the metabolic syndrome (MtS) in obese European adolescents in addition to previous unsuccessful lifestyle intervention.Design and methodsAfter 6 months of multiprofessional lifestyle intervention, 70 out of 86 adolescents without improvement in body mass index (BMI) and HOMA-IR were randomized into either the placebo (n=34) or the metformin group (2×500 mg/day,n=36) in addition to ongoing lifestyle intervention for another 6 months.ResultsAge was 13.8 years, BMI was 33.1 kg/m2, 65% were female, and 89% were Caucasians. During lifestyle intervention alone, BMI and HOMA-IR deteriorated significantly. In the subsequent medication period, HOMA-IR and fasting insulin improved similarly in the placebo and metformin groups (HOMA-IR decreased 73 vs 54% respectively in metformin versus placebo;P=0.048), but BMI remained unchanged. The insulin sensitivity index, however, only improved in the metformin group. High fasting insulin is correlated with a subsequent BMI increase irrespective of the medication. MtS remained unchanged.ConclusionsObese European adolescents' insulin sensitivity improved without weight change during placebo or metformin intervention in addition to lifestyle intervention. Most differences did not reach statistical significance, probably due to improved compliance with lifestyle intervention as a placebo effect. In addition, the metformin dose may be too low.

Immunosuppressive drug (ISD)-associated gastrointestinal disorders are a relevant risk factor for graft loss or patient death. The pathomechanisms and the incidence of post-transplantation diarrhea remain to be fully understood. The aim of this study was to characterize the impact of cyclosporine A, tacrolimus (TAC), mycophenolate mofetil (MMF), enteric coated mycophenolic acid (EC-MPA), sirolimus, everolimus (EVE) and fingolimod (FTY 720) on small and large bowel transport and barrier function. Functions of the small bowel and distal colon of Wistar rats treated for 14 days with one of the drug were analyzed using Ussing chamber method. In detail, the glucose and sodium absorption, chloride secretion, and barrier function were compared. Bowel functions were investigated by inhibition or activation of the electrogenic epithelial transport, as well as by measuring transepithelial H(3) -lactulose flux. TAC altered glucose absorption; EVE glucose absorption, small bowel barrier function and chloride secretion; MMF small bowel barrier function; and EC-MPA glucose absorption and the small bowel barrier function. Drug effects were partially dose-dependent. In conclusion, different ISD, such as TAC, EVE, MMF, or EC-MPA lead to different and specific patterns of pathophysiologic changes of small and large bowel barrier and transport function.

Current research has entered into an unprecedented territory of analytical possibilities represented by so called “omics” technologies, allowing the examination of patients and their individual diseases on a previously unimaginable level. This development represents a serious challenge considering established trial designs and research conduct, particularly in early phase clinical trials, since novel theranostics (biomarker based allocation therapies) in principle would allow for patient selection far beyond traditional stratification approaches; further, many different therapeutic combinatorial therapies cannot be easily evaluated in a traditional way within a reasonable timeframe. The summit of this paradigm is biomarker-based selection and manufacturing of a previously undefined drug product directly adapted to patient- and disease-specific features. In our view, such an approach is ideally suited for cancer immunotherapy, since both malignancies and the human immune system require a high level of individuality. Hence, defining naturally presented HLA-Ligands specific for individual malignancies and manufacturing respective T cell targets according to current Good Manufacturing Practice (GMP) standards formulated as a multi-peptide vaccine in a clinical trial is a completely new state of the art approach. On this background, we designed a pilot clinical trial and implemented the required environment, addressing patients with particularly high unmet medical need and exceedingly high relapse rates in an adjuvant setting. The trial follows a platform design including different disease entities, encompassing non-small cell lung cancer (NSCLC), advanced colorectal cancer (CRC), triple negative breast cancer, cholangiocarcinoma, hepatocellular carcinoma (HCC) and high-risk soft tissue sarcoma. Target selection follows a five-pronged approach and is based on analyzing patient autologous tumor material on different omics levels, including the whole exome and transcriptome as well as the HLA-ligandome (comprehensive analysis of the naturally presented HLA ligands on tumor (and benign) tissue by tandem mass spectrometry) to select ideal immunological targets. Further, this trial will endorse a three tier escalation protocol featuring an individual multi-peptide vaccine with Montanide ISA 51 VG and topical imiquimod in a first step, combined with the novel lipopeptide adjuvant XS-15 (TLR7 ligand) and finally introducing a checkpoint inhibitor as a third tier. This pilot trial will primarily focus on endpoints safety and feasibility but endorse various secondary objectives including detailed immunomonitoring of induced vaccine responses and other immune markers. The HCC trial part is supported by the European Commission's 7th Framework Program (www.hepavac.eu). Citation Format: Sebastian Haen, Markus W. Löffler, Oliver Kohlbacher, Sven Nahnsen, Christopher Mohr, Monika Stieglbaueren, Patricia Hrstic, Luigi Buonaguro, Peter Martus, Maik Häntschel, Cécile Gouttefangeas, Stefan Beckert, Alfred Königsrainer, Stefan Stevanovic, Lothar Kanz, Hans-Georg Rammensee. Phase I trial to evaluate the feasibility and safety of an individualized peptide vaccine of unmodified cancer antigens: PepIVAC-01 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT057.

Background The Work Ability Index (WAI) is a well-established instrument to measure work ability. However, the dimensionality of the WAI remains controversial. Aims To identify the dimensionality of the WAI and to investigate dependencies of factors and subscales. Methods The sample analysed in this study consisted of 371 subjects of different occupational groups (teachers, office workers, nursery school teachers and managers). The WAI was measured for all subgroups. Psychometric characteristics of the WAI were investigated using factor analyses with different numbers and different patterns of dependency among the factors. Chi-square analysis and the Comparative Fit Index were used to statistically assess fit quality. Results The group of managers had to be excluded from the analysis as their results were probably overoptimistic due to reporting bias; thus, 324 subjects entered. The one-factor model and an orthogonal two-factor model did not fit the observed correlational structures. A satisfactory fit was obtained using a two-dimensional model with correlated factors. These factors could be interpreted as subjectively estimated work ability and objective health status. Only five of seven items of the WAI could be related unambiguously to one of both factors. Conclusions From our study, we conclude that using only the total score of the WAI is not adequate for population analysis of and assessment of work ability to individuals. Instead, the two-dimensional structure of the instrument must be taken into account.

9501Background: The multicenter DeCOG-SLT trial assessed in a randomized phase 3 trial whether complete lymph node dissection (CLND) resulted in increased survival compared with observation in pati...

Lock JF, Malinowski M, Schwabauer E, Martus P, Pratschke J, Seehofer D, Puhl G, Neuhaus P, Stockmann M. Initial liver graft function is a reliable predictor of tacrolimus trough levels during the first post-transplant week. Clin Transplant 2011: 25: 436–443. © 2010 John Wiley & Sons A/S. Abstract: The narrow therapeutic range of tacrolimus requires careful management after liver transplantation (LT). The aim of this study was to investigate the influence of graft function on tacrolimus trough levels during the first post-transplant week. Ninety-three patients receiving deceased-donor LT were observed in a prospective observational study. Graft function was determined by the new LiMAx test (maximal liver function capacity). Significant correlations between LiMAx readouts and consecutive tacrolimus levels, up to r = −0.529 (p

Signature metabolites provide direct geochemical indication that in-situ biodegradation of released organic compounds (e.g., oil and its refined products) is occurring. Experience shows that monitored natural attenuation site conditions are often more complex than in theory and often require a more profound comprehension of the governing natural attenuation processes. Frequently, there is lack of direct proof that contaminant degradation (mainly through biodegradation) is occurring. Advanced tools are emerging that aim to provide answers about whether contaminants of concern are actually (bio)degraded and to the extent. Signature metabolite analysis provides direct proof of mineral oil hydrocarbon biodegradation and is among these advanced tools. Yet, during the previous 15 years, metabolite analysis has only been used sporadically in research projects. The target metabolites consist of aromatic acids such as benzoates and benzylsuccinates and uniquely indicate in-situ biodegradation of individual contami...

The frequency of meningeal dissemination (MD) in primary CNS lymphoma (PCNSL), its prognostic impact, and optimal management have not been defined thus far. In 69 of 92 (75%) immunocompetent patients, primarily diagnosed with PCNSL at our institution between January 1994 and February 2007, cerebrospinal fluid was analyzed for MD. MD was found by cytomorphology in 7/63 (11%), by immunophenotyping in 1/32 (3%), and by PCR of the IgH CDR III region in 6/37 (16%). Neuroradiologic examination revealed MD in 3 of 69 patients (4%). Median event-free survival (EFS) of patients with MD diagnosed by any of the methods was 26 months, of those without MD 34.1 months (P = .24); median overall survival (OAS) of these two patients' groups was 45.5 and 42.5 months, respectively (P = .34). Patients with cytomorphologic proof of MD had a median EFS of 15.4 months and OAS of 18.5 months, those without MD 34.3 and 45 months (P = .018 and .017, respectively). We found a low frequency of MD despite the use of putatively sensitive diagnostic methods. No impact on outcome was seen for MD, diagnosed by any of the methods used; however, patients with cytomorphologic proof of MD had a significantly shorter median EFS and OAS.