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Background Peritonitis is responsible for thousands of deaths annually in Germany alone. Even source control (SC) and antibiotic treatment often fail to prevent severe sepsis or septic shock, and this situation has hardly improved in the past two decades. Most experimental immunomodulatory therapeutics for sepsis have been aimed at blocking or dampening a specific pro-inflammatory immunological mediator. However, the patient collective is large and heterogeneous. There are therefore grounds for investigating the possibility of developing personalized therapies by classifying patients into groups according to biomarkers. This study aims to combine an assessment of the efficacy of treatment with a preparation of human immunoglobulins G, A, and M (IgGAM) with individual status of various biomarkers (immunoglobulin level, procalcitonin, interleukin 6, antigen D-related human leucocyte antigen (HLA-DR), transcription factor NF-κB1, adrenomedullin, and pathogen spectrum). Methods/design A total of 200 patients with sepsis or septic shock will receive standard-of-care treatment (SoC). Of these, 133 patients (selected by 1:2 randomization) will in addition receive infusions of IgGAM for 5 days. All patients will be followed for approximately 90 days and assessed by the multiple-organ failure (MOF) score, by the EQ QLQ 5D quality-of-life scale, and by measurement of vital signs, biomarkers (as above), and survival. Discussion This study is intended to provide further information on the efficacy and safety of treatment with IgGAM and to offer the possibility of correlating these with the biomarkers to be studied. Specifically, it will test (at a descriptive level) the hypothesis that patients receiving IgGAM who have higher inflammation status (IL-6) and poorer immune status (low HLA-DR, low immunoglobulin levels) have a better outcome than patients who do not receive IgGAM. It is expected to provide information that will help to close the knowledge gap concerning the association between the effect of IgGAM and the presence of various biomarkers, thus possibly opening the way to a personalized medicine. Trial registration EudraCT, 2016–001788-34; ClinicalTrials.gov, NCT03334006. Registered on 17 Nov 2017. Trial sponsor: RWTH Aachen University, represented by the Center for Translational & Clinical Research Aachen (contact Dr. S. Isfort). Electronic supplementary material The online version of this article (10.1186/s13063-019-3244-4) contains supplementary material, which is available to authorized users.

Axial low back pain can be considered as a syndrome with both nociceptive and neuropathic pain components (mixed-pain). Especially neuropathic pain comprises a therapeutic challenge in practical experience and may explain why pharmacotherapy in back pain is often disappointing for both the patient and the therapist. This survey uses epidemiological and clinical data on the symptomatology of 1083 patients with axial low back pain from a cross sectional survey (painDETECT). Objectives were (1) to estimate whether neuropathic pain contributes to axial low back pain and if so to what extent. (2) To detect subgroups of patients with typical sensory symptom profiles and to analyse their demographic data and co-morbidities. (3) To compare patients with and without prior intervertebral disc surgery (IVD). Neuropathic pain components could be detected in 12% of the entire cohort. Cluster analyses of these patients revealed five distinct subgroups of patients showing a characteristic sensory profile, i.e. a typical constellation and combination of symptoms. All subgroups occurred in relevant numbers and some showed distinct neuropathic characteristics while others showed nociceptive features. Post-IVD-surgery patients showed a tendency to score more "neuropathic" than patients without surgery (not statistically significant). Axial low back pain has a high prevalence of co-morbidities with implication on therapeutic aspects. From these data it can be concluded that sensory profiles based on descriptor severity may serve as a better predictor for therapy assessment than pain intensity or sole diagnosis alone. Standardized phenotyping of pain symptoms with easy tools may help to develop an individualized therapy leading to a higher success rate in pharmacotherapy of axial low back pain.

The mechanism of thermally mediated CO insertion into vinylcyclopropanes by Fe(CO) 5 has been studied using deuterium labelled starting materials. The broad distribution of deuterium in the enone products suggests formation of an intermediate iron π-allyl hydride complex that is capable of internal deuterium delivery to several positions. The mechanistic differences between thermal and photoinduced CO insertion into vinylcyclopropanes are discussed.

Background Patients with diabetic neuropathy (DPN) and fibromyalgia differ substantially in pathogenetic factors and the spatial distribution of the perceived pain. We questioned whether, despite these obvious differences, similar abnormal sensory complaints and pain qualities exist in both entities. We hypothesized that similar sensory symptoms might be associated with similar mechanisms of pain generation. The aims were (1) to compare epidemiological features and co-morbidities and (2) to identify similarities and differences of sensory symptoms in both entities. Methods The present multi-center study compares epidemiological data and sensory symptoms of a large cohort of 1434 fibromyalgia patients and 1623 patients with painful diabetic neuropathy. Data acquisition included standard demographic questions and self-report questionnaires (MOS sleep scale, PHQ-9, PainDETECT). To identify subgroups of patients with characteristic combinations of symptoms (sensory profiles) a cluster analysis was performed using all patients in both cohorts. Results Significant differences in co-morbidities (depression, sleep disturbance) were found between both disorders. Patients of both aetiologies chose very similar descriptors to characterize their sensory perceptions. Burning pain, prickling and touch-evoked allodynia were present in the same frequency. Five subgroups with distinct symptom profiles could be detected. Two of the subgroups were characteristic for fibromyalgia whereas one profile occurred predominantly in DPN patients. Two profiles were found frequently in patients of both entities (20-35%). Conclusions DPN and fibromyalgia patients experience very similar sensory phenomena. The combination of sensory symptoms - the sensory profile - is in most cases distinct and almost unique for each one of the two entities indicating aetiology-specific mechanisms of symptom generation. Beside the unique aetiology-specific sensory profiles an overlap of sensory profiles can be found in 20-35% of patients of both aetiologies.

Objectives. Patients with FM are heterogeneous. They present with a variety of pain qualities, sensory abnormalities and additional comorbidities. The aim was to identify clinically distinguishable subgroups of patients. Methods. This investigation uses epidemiological and clinical data of 3035 FM patients from a cross-sectional survey (painDETECT) to (i) describe characteristic epidemiological data and comorbidities and (ii) detect subgroups of patients with typical patterns of sensory symptoms and comorbidities. Results. Clinically relevant sensory abnormalities (strongly, very strongly present) included pressure pain (58%), prickling (33%), burning (30%) and thermal hypersensitivity (24%). Pain attacks were complained by 40% of patients. Moderate to severe comorbid depression occurred in 66% of patients. Only 30% of the patients had optimal sleep. A hierarchical cluster analysis using descriptors of sensory abnormalities as well as the extent of comorbidities revealed five distinct subgroups of patients showing a characteristic clinical profile. Four subgroups of patients suffer from severe sensory disturbances in various combinations but lack pronounced comorbidities. In one subgroup, however, severe comorbidities dominate the clinical picture. Differences in pathophysiological mechanisms of pain generation can be attributed to each subgroup. Conclusions. The results of this study indicate that FM patients can be classified on the basis of their sensory symptoms and comorbidities by the use of a patient-reported questionnaire. Subgrouping of patients with FM may be used for future research and to tailor optimal treatment strategies for the appropriate patient.