[Prehospital care of anaphylactic reactions by the air rescue and ground-based emergency services Dresden : An analysis of treatment and outcome]. / Präklinische Versorgung von anaphylaktischen Reaktionen durch die Dresdner Luft- und Bodenrettung : Analyse von Therapie und Outcome.

BACKGROUND: Anaphylaxis can lead to a life-threatening situation. Therefore, rapid diagnosis and emergency treatment is indicated. Immediate treatment with intramuscular adrenaline (or intravascularly with sufficient medical expertise) in anaphylaxis with cardiovascular and/or respiratory symptoms is recommended by various guidelines. Previous studies have shown that anaphylaxis is often not treated according to guidelines and that adrenaline in particular is rarely administered. OBJECTIVE: The aim of the study was to investigate the data on emergency treatment and outcomes of patients with anaphylaxis by the air rescue and ground-based emergency services Dresden. Moreover, the results of the air- and ground-based services were compared. The focus was on administration of adrenaline and outcomes. MATERIALS AND METHODS: Data from the ground-based emergency service Dresden (from 2012 to 2016) and the air rescue service Dresden (from 2008 to 2015) related to anaphylactic reactions were analyzed retrospectively. The severity of the anaphylaxis, the emergency medication administered, further monitoring, and outcomes were analyzed. RESULTS: Data from 152 adults/29 children were analyzed for air rescue and 1131 adults/223 children for the ground-based emergency service. Adults with grade II-IV anaphylaxis received adrenaline in 19% (air rescue) and 7% (ground rescue) of cases. Children with grade II-IV anaphylaxis received adrenaline in 7% (air rescue) and 8% (ground rescue) of cases. Immediate drug therapy led to an improvement in general condition in 96-98% (air rescue) and 72-77% (ground-based emergency service) of cases. A significant correlation was found between the administration of adrenaline and the improvement in outcome in the ground-based emergency cohort. CONCLUSION: Guideline-compliant first-line therapy with adrenaline was not performed in the majority of the cases analyzed in this study. The significant effect of adrenaline on outcome demonstrated in this study emphases the need to improve the emergency treatment of anaphylactic reactions.

Stress of emergency physicians during helicopter operations: impact of patients' diagnoses, severity of diagnoses, and physicians' work experience.

PURPOSE: Emergency physicians are in danger of developing illnesses due to stress in their demanding work environment. Until today, scholars have not identified stressors or resilience factors that qualify to promote the preservation of emergency physicians' well-being. Therefore, potential influencing variables such as patients' diagnoses, the severity of diagnoses, as well as physicians' work experience have to be considered. The present study aims at investigating emergency physicians in the Helicopter Emergency Medical Service (HEMS)' autonomic nervous system activity during emergency operations in one shift with respect to patients' diagnoses, severity of diagnoses, and physicians' work experience. METHODS: Measurement of HRV (employing the parameters RMSSD and LF/HF) for 59 EPs (age: M = 39.69, SD = 6.19) was performed during two complete air-rescue-days, the alarm and landing phase being investigated in particular. Besides patients' diagnoses, the National Advisory Committee for Aeronautics Score (NACA) was included as an indicator for severity. Diagnoses' and NACA's effect on HRV were examined using a linear mixed model. RESULTS: Both HRV parameters indicate a significant decrease of the parasympathetic nervous system as a function of the diagnoses. Furthermore, high NACA scores (≥ V) predicted a significantly lower HRV. In addition, a lower HRV/RMSSD with increasing work experience was observed as well as a positive association between physicians' work experience and sympathetic activation (LF/HF). CONCLUSION: The present study showed that pediatric diagnoses as well as time-critical diagnoses are most stressful and have the highest impact on the physicians' ANS. This knowledge allows the development of specific training to reduce stress.

Analysis of Air Rescue for Offshore Wind Energy: A Retrospective Analysis of Structural and Process Quality for the Years 2014 to 2017.

In order to achieve the emission targets required by the German Federal Environment Agency (Umweltbundesamt), the offshore wind industry has become 1 of the central building blocks of the so-called "energy turnaround." After the first offshore wind farm (OWF), Alpha Ventus, started operation in 2010, the number of OWFs in the North Sea and Baltic Sea has grown steadily. Because of the ongoing growth of the industry, the number of workers on-site has more than quadrupled in recent years. Although the majority of OWFs are located in the exclusive economic zone up to 130 km from the mainland, the same legal provisions of the Occupational Health and Safety Act (Arbeitsschutzgesetz) apply here as on the mainland. This means that the operators of the wind farms are legally obligated to maintain a seamless rescue chain. Because of the distance to the mainland, rescue helicopters are the means of choice to ensure prompt emergency preclinical care and, if necessary, rapid evacuation. The company Northern HeliCopter GmbH, part of the DRF Luftrettung since 2019, offers as part of WINDEACare rescue helicopters stationed at 3 locations on the North Sea and Baltic Sea to its contract partners an emergency medical staffed air rescue service, which is operational 24 hours a day, 365 days a year. This article is the first to provide a detailed overview of a new field in prehospital emergency care on the high seas and, to this end, has recorded all offshore missions performed from 2014 through 2017 with evaluation of related medical and aeronautical data.

Structure of In Vitro-Synthesized Cellulose Fibrils Viewed by Cryo-Electron Tomography and 13C Natural-Abundance Dynamic Nuclear Polarization Solid-State NMR.

Cellulose, the most abundant biopolymer, is a central source for renewable energy and functionalized materials. In vitro synthesis of cellulose microfibrils (CMFs) has become possible using purified cellulose synthase (CESA) isoforms from Physcomitrium patens and hybrid aspen. The exact nature of these in vitro fibrils remains unknown. Here, we characterize in vitro-synthesized fibers made by CESAs present in membrane fractions of P. patens over-expressing CESA5 by cryo-electron tomography and dynamic nuclear polarization (DNP) solid-state NMR. DNP enabled measuring two-dimensional 13C-13C correlation spectra without isotope-labeling of the fibers. Results show structural similarity between in vitro fibrils and native CMF in plant cell walls. Intensity quantifications agree with the 18-chain structural model for plant CMF and indicate limited fibrillar bundling. The in vitro system thus reveals insights into cell wall synthesis and may contribute to novel cellulosic materials. The integrated DNP and cryo-electron tomography methods are also applicable to structural studies of other carbohydrate-based biomaterials.

Frontier atmosphere: observation and regret at Chinese weather stations in Tibet, 1939-1949.

Across Tibet during the 1940s, young Han Chinese weather observers became stranded at their weather stations, where they faced illness, poverty and isolation as they pleaded with their superiors for relief. Building on the premise that China exercised 'imperial nationalism' in Tibet, and in light of scholarship that emphasizes the desirous 'gaze' of imperial observers toward the frontier, this essay considers how the meteorological archive might disrupt our understanding of the relationship between observation and empire. Meteorology presented a new way of viewing the landscape that deliberately disregarded the embodied experience of the observer in favour of instrument-mediated readings. The process produced a bifurcated archive, in which stations disseminated quantitative weather charts as a matter of public interest while privately recording the embodied and often miserable experiences of observational staff on the frontier. Unpublished letters between observers and supervisors offer a rare glimpse into the frontier as experienced by reluctant or unwilling agents of the state.

Just in Time Radiology Decision Support Using Real-time Data Feeds.

Ready access to relevant real-time information in medical imaging offers several potential benefits. Knowing both when important information will be available and that important information is available can facilitate optimization of workflow and management of time. Unexpected findings, as well as deficiencies in reporting and documentation, can be immediately managed. Herein, we present our experience developing and implementing a real-time web-centric dashboard system for radiologists, clinicians, and support staff. The dashboards are driven by multi-sourced HL7 message streams that are monitored, analyzed, aggregated, and transformed into multiple real-time displays to improve operations within our department. We call this framework Pipeline. Ruby on Rails, JavaScript, HTML, and SQL serve as the foundations of the Pipeline application. HL7 messages are processed in real-time by a Mirth interface engine which posts exam data into SQL. Users utilize web browsers to visit the Ruby on Rails-based dashboards on any device connected to our hospital network. The dashboards will automatically refresh every 30 seconds using JavaScript. The Pipeline application has been well received by clinicians and radiologists.

Stress load of emergency service: effects on the CAR and HRV of HEMS emergency physicians on different working days (N = 20).

PURPOSE: The occupation of the emergency physicians (EPs) of helicopter emergency medical services (HEMS) can be characterized as a high-strain occupation (Karasek in Adm Sci Q 24(2):285-308. https://doi.org/10.2307/2392498 , 1979). Therefore, the aim of this study was to measure and compare the stress load of the EPs of HEMS on duty on air ambulance workdays and on 2 control days. METHODS: In this field study (within-subjects design), hormonal, physiological, and self-perceived stress levels of 20 EPs [3 females, 17 males; mean age (M) = 44.95 years, SD = 4.80, 95% confidence interval (CI) (42.71, 47.19)] of HEMS, were recorded on different test days. Measurements of the cortisol awakening response (CAR) and the heart rate variability (HRV) were performed while on duty on the air ambulance and during workdays at the outpatient clinic as well as at home on days of rest. RESULTS: There were significant differences in the CAR (area under the curve with respect to ground F(2,38) = 12.81, p < 0.001) between the 3 test days with the highest values on the workday at the outpatient clinic [M = 81.24; 98.75% CI (61.24, 101.24)] and not on the air ambulance day [M = 61.82; 98.75% CI (45.18, 78.46)] or on the day of rest [M = 52.96; 98.75% CI (38.17, 67.76)]. In addition, the HRV parameter SDNN [F(2,38) = 6.369; p = 0.004] presented significant differences between the 3 test days with lower levels on the day at the outpatient clinic [M = 101.44; 98.75% CI (83.50, 119.38)] in contrast to the air ambulance day [M = 120.16; 98.75% CI (100.02, 140.30)] and to the resting day [M = 123.79; 98.75% CI (106.49, 141.10)]. Furthermore, there were significant differences in the HRV parameter LF/HF [F(2,38) = 6.215; p = 0.005] between the 3 testing days with the highest values on the workday at the outpatient clinic [M = 8.69; 98.75% CI (6.29, 11.09)] compared to the air ambulance day [M = 6.54; 98.75% CI (4.50, 8.57)] and the day of rest [M = 6.43; 98.75% CI (4.57, 8.29)]. CONCLUSIONS: Compared with the standard values and previous studies, EPs of HEMS have an increase in hormonal reactivity in the morning and a lack of recovery of the ANS. It can be concluded that-with respect to the psychobiological stress model by McEwen and Lasley (The end of stress as we know it, National Academic Press, Washington, 2003)-work-related stressors persist too long or the stress response is exaggerated (allostatic load) due to chronic stress induction and lack of recovery.

Evaluation of Gadolinium Deposition in the Brain After MR Arthrography.

OBJECTIVE: Although significant investigation has been done into the deposition of gadolinium in the brains of patients receiving IV gadolinium, there is little research concerning nonintravenous uses of gadolinium, specifically in conjunction with musculoskeletal MR arthrography. Although small in volume, intraarticular administration is an off-label use of gadolinium, necessitating careful scrutiny for patient safety. Thus, we investigated the relationship between intraarticular gadolinium administration during MR arthrography and the presence of intracranial gadolinium deposition on subsequent brain MRI. MATERIALS AND METHODS: An institutional review board-approved retrospective study was performed of patients with no history of gadolinium exposure who underwent MR arthrography from 2006 to 2016 followed by an unenhanced brain MRI examination. ROIs were manually placed within bilateral dentate nuclei (DN), bilateral globus pallidi (GP), bilateral thalami, bilateral middle cerebral peduncles (MCP), and the central pons (CP) on T1-weighted sequences. The left and right ROIs were averaged, and ratios of signal intensity were calculated for DN/MCP, DN/CP, GP/MCP, GP/CP, thalamus/MCP, and thalamus/CP. Similar ROIs were placed and ratios calculated for age-matched control subjects who had a history of brain MRI but no prior gadolinium exposure. We used t testing to compare signal intensity ratios between patients and control subjects. RESULTS: A total of 31 patients met the inclusion criteria. We found no significant difference in signal intensity between patients and control subjects for DN/MCP (p = 0.40), DN/CP (p = 0.76), GP/MCP (p = 0.51), GP/CP (p = 0.86), thalamus/MCP (p = 0.93), and thalamus/CP (p = 0.30). CONCLUSION: No association was found between intraarticular gadolinium administration for MR arthrography and detectable gadolinium deposition within the brain.

The Transcription Factor ARID3a Is Important for In Vitro Differentiation of Human Hematopoietic Progenitors.

We recently reported that the transcription factor ARID3a is expressed in a subset of human hematopoietic progenitor stem cells in both healthy individuals and in patients with systemic lupus erythematosus. Numbers of ARID3a(+) lupus hematopoietic stem progenitor cells were associated with increased production of autoreactive Abs when those cells were introduced into humanized mouse models. Although ARID3a/Bright knockout mice died in utero, they exhibited decreased numbers of hematopoietic stem cells and erythrocytes, indicating that ARID3a is functionally important for hematopoiesis in mice. To explore the requirement for ARID3a for normal human hematopoiesis, hematopoietic stem cell progenitors from human cord blood were subjected to both inhibition and overexpression of ARID3a in vitro. Inhibition of ARID3a resulted in decreased B lineage cell production accompanied by increases in cells with myeloid lineage markers. Overexpression of ARID3a inhibited both myeloid and erythroid differentiation. Additionally, inhibition of ARID3a in hematopoietic stem cells resulted in altered expression of transcription factors associated with hematopoietic lineage decisions. These results suggest that appropriate regulation of ARID3a is critical for normal development of both myeloid and B lineage pathways.

Emotion and aggressive intergroup cognitions: The ANCODI hypothesis.

Previous research has suggested an important role for the emotion of hatred in intergroup aggression. Recent theoretical and empirical work has strongly suggested that the combination of anger, contempt, and disgust (ANCODI) comprise the basic elements of hatred, and are the key emotions associated with intergroup aggression. No study, however, has provided evidence that these emotions cause hostile cognitions about specific groups. We report two studies that provide initial evidence. In both, participants were members of ideologically motivated groups and were primed with ANCODI. In Study 1 participants primed with ANCODI produced more aggressive cognitions relative to their opponent outgroup than a neutral outgroup; this effect did not occur for participants primed with fear-sadness. In Study 2 participants primed with ANCODI engaged in more competitive decision making against their opponent outgroups than a neutral outgroup; this effect did not occur for participants primed with disgust only. These findings contribute to the literature on the role of emotion in intergroup aggression and hostility, and provide a more nuanced view of the role of emotions in intergroup relations, possibly identifying the basic emotional elements of hatred. Aggr. Behav. 43:93-107, 2017. © 2016 Wiley Periodicals, Inc.

Cultivation of an Adaptive Domestic Network for Surveillance and Evaluation of Emerging Infections.

Accomplishments of this program have provided numerous dividends and might benefit areas outside infectious diseases.

Loss of cone cyclic nucleotide-gated channel leads to alterations in light response modulating system and cellular stress response pathways: a gene expression profiling study.

The cone photoreceptor cyclic nucleotide-gated (CNG) channel is essential for central and color vision and visual acuity. Mutations in the channel subunits CNGA3 and CNGB3 are associated with achromatopsia and cone dystrophy. We investigated the gene expression profiles in mouse retina with CNG channel deficiency using whole genome expression microarrays. As cones comprise only 2 to 3% of the total photoreceptor population in the wild-type mouse retina, the mouse lines with CNG channel deficiency on a cone-dominant background, i.e. Cnga3-/-/Nrl-/- and Cngb3-/-/Nrl-/- mice, were used in our study. Comparative data analysis revealed a total of 105 genes altered in Cnga3-/-/Nrl-/- and 92 in Cngb3-/-/Nrl-/- retinas, relative to Nrl-/- retinas, with 27 genes changed in both genotypes. The differentially expressed genes primarily encode proteins associated with cell signaling, cellular function maintenance and gene expression. Ingenuity pathway analysis (IPA) identified 26 and 9 canonical pathways in Cnga3-/-/Nrl-/- and Cngb3-/-/Nrl-/- retinas, respectively, with 6 pathways being shared. The shared pathways include phototransduction, cAMP/PKA-mediated signaling, endothelin signaling, and EIF2/endoplasmic reticulum (ER) stress, whereas the IL-1, CREB, and purine metabolism signaling were found to specifically associate with Cnga3 deficiency. Thus, CNG channel deficiency differentially regulates genes that affect cell processes such as phototransduction, cellular survival and gene expression, and such regulations play a crucial role(s) in the retinal adaptation to impaired cone phototransduction. Though lack of Cnga3 and Cngb3 shares many common pathways, deficiency of Cnga3 causes more significant alterations in gene expression. This work provides insights into how cones respond to impaired phototransduction at the gene expression levels.

The canonical Wnt pathway shapes niches supportive of hematopoietic stem/progenitor cells.

Considerable information has accumulated about components of BM that regulate the survival, self-renewal, and differentiation of hematopoietic cells. In the present study, we investigated Wnt signaling and assessed its influence on human and murine hematopoiesis. Hematopoietic stem/progenitor cells (HSPCs) were placed on Wnt3a-transduced OP9 stromal cells. The proliferation and production of B cells, natural killer cells, and plasmacytoid dendritic cells were blocked. In addition, some HSPC characteristics were maintained or re-acquired along with different lineage generation potentials. These responses did not result from direct effects of Wnt3a on HSPCs, but also required alterations in the OP9 cells. Microarray, PCR, and flow cytometric experiments revealed that OP9 cells acquired osteoblastic characteristics while down-regulating some features associated with mesenchymal stem cells, including the expression of angiopoietin 1, the c-Kit ligand, and VCAM-1. In contrast, the production of decorin, tenascins, and fibromodulin markedly increased. We found that at least 1 of these extracellular matrix components, decorin, is a regulator of hematopoiesis: upon addition of this proteoglycan to OP9 cocultures, decorin caused changes similar to those caused by Wnt3a. Furthermore, hematopoietic stem cell numbers in the BM and spleen were elevated in decorin-knockout mice. These findings define one mechanism through which canonical Wnt signaling could shape niches supportive of hematopoiesis.

Functional characterization of the MECP2/IRAK1 lupus risk haplotype in human T cells and a human MECP2 transgenic mouse.

Genetic polymorphism in MECP2/IRAK1 on chromosome Xq28 is a confirmed and replicated susceptibility locus for lupus. High linkage disequilibrium in this locus suggests that both MECP2 and IRAK1 are candidate genes for the disease. DNA methylation changes in lupus T cells play a central role in the pathogenesis of lupus, and MeCp-2 (encoded by MECP2) is a master regulator of gene expression and is also known to recruit DNA methyltransferase 1 (DNMT1) during DNA synthesis. Using human T cells from normal individuals with either the lupus risk or the lupus protective haplotype in MECP2/IRAK1, we demonstrate that polymorphism in this locus increases MECP2 isoform 2 mRNA expression in stimulated but not unstimulated T cells. By assessing DNA methylation levels across over 485,000 methylation sites across the entire genome, we further demonstrate that the lupus risk variant in this locus is associated with significant DNA methylation changes, including in the HLA-DR and HLA-DQ loci, as well as interferon-related genes such as IFI6, IRF6, and BST2. Further, using a human MECP2 transgenic mouse, we show that overexpression of MECP2 alters gene expression in stimulated T cells. This includes overexpression of Eif2c2 that regulates the expression of multiple microRNAs (such as miR-21), and the histone demethylase Jhdm1d. In addition, we show that MECP2 transgenic mice develop antinuclear antibodies. Our data suggest that the lupus-associated variant in the MECP2/IRAK1 locus has the potential to affect all 3 epigenetic mechanisms: DNA methylation, microRNA expression, and histone modification. Importantly, these data support the notion that variants within the MECP2 gene can alter DNA methylation in other genetic loci including the HLA and interferon-regulated genes, thereby providing evidence for genetic-epigenetic interaction in lupus.

Inflammation and neurological disease-related genes are differentially expressed in depressed patients with mood disorders and correlate with morphometric and functional imaging abnormalities.

Depressed patients show evidence of both proinflammatory changes and neurophysiological abnormalities such as increased amygdala reactivity and volumetric decreases of the hippocampus and ventromedial prefrontal cortex (vmPFC). However, very little is known about the relationship between inflammation and neuroimaging abnormalities in mood disorders. A whole genome expression analysis of peripheral blood mononuclear cells yielded 12 protein-coding genes (ADM, APBB3, CD160, CFD, CITED2, CTSZ, IER5, NFKBIZ, NR4A2, NUCKS1, SERTAD1, TNF) that were differentially expressed between 29 unmedicated depressed patients with a mood disorder (8 bipolar disorder, 21 major depressive disorder) and 24 healthy controls (HCs). Several of these genes have been implicated in neurological disorders and/or apoptosis. Ingenuity Pathway Analysis yielded two genes networks, one centered around TNF with NFKß, TGFß, and ERK as connecting hubs, and the second network indicating cell cycle and/or kinase signaling anomalies. fMRI scanning was conducted using a backward-masking task in which subjects were presented with emotionally-valenced faces. Compared with HCs, the depressed subjects displayed a greater hemodynamic response in the right amygdala, left hippocampus, and the ventromedial prefrontal cortex to masked sad versus happy faces. The mRNA levels of several genes were significantly correlated with the hemodynamic response of the amygdala, vmPFC and hippocampus to masked sad versus happy faces. Differentially-expressed transcripts were significantly correlated with thickness of the left subgenual ACC, and volume of the hippocampus and caudate. Our results raise the possibility that molecular-level immune dysfunction can be mapped onto macro-level neuroimaging abnormalities, potentially elucidating a mechanism by which inflammation leads to depression.

National climate: Zhu Kezhen and the framing of the atmosphere in modern China.

Can climate be Chinese, and if so, then how? Drawing on personal writings, popular discourse, and scientific reports, this essay considers the work of early Chinese meteorologists in relation to the revolutionary national politics of the early twentieth century. Historians of China have established that nationalism motivated the pursuit of meteorology and other natural sciences, but I advance the more radical position that there was no clear distinction between the practice of climate science and the political ideology that motivated it. With special attention to the career and legacy of Zhu Kezhen from the Xinhai Revolution through World War II, I test this thesis in two arenas: Chinese meteorologists' production of spatial knowledge, and their production of cultural knowledge. The nation was integral to the questions, methods, and analyses of atmospheric science, which helped to reify the Chinese nation-state.

Estrogen receptor signaling promotes dendritic cell differentiation by increasing expression of the transcription factor IRF4.

During inflammation, elevated granulocyte macrophage-colony-stimulating factor (GM-CSF) directs the development of new dendritic cells (DCs). This pathway is influenced by environmental factors, and we previously showed that physiologic levels of estradiol, acting through estrogen receptor alpha (ERalpha), promote the GM-CSF-mediated differentiation of a CD11b(+) DC subset from myeloid progenitors (MPs). We now have identified interferon regulatory factor 4 (IRF4), a transcription factor induced by GM-CSF and critical for CD11b(+) DC development in vivo, as a target of ERalpha signaling during this process. In MPs, ERalpha potentiates and sustains GM-CSF induction of IRF4. Furthermore, retroviral delivery of the Irf4 cDNA to undifferentiated ERalpha(-/-) bone marrow cells restored the development of the estradiol/ERalpha-dependent DC population, indicating that an elevated amount of IRF4 protein substitutes for ERalpha signaling. Thus at an early stage in the MP response to GM-CSF, ERalpha signaling induces an elevated amount of IRF4, which leads to a developmental program underlying CD11b(+) DC differentiation.

External Qi of Yan Xin Qigong induces cell death and gene expression alterations promoting apoptosis and inhibiting proliferation, migration and glucose metabolism in small-cell lung cancer cells.

Small-cell lung cancer (SCLC) is a highly malignant carcinoma with poor long-term survival. Effective treatment remains highly demanded. In the present study, we demonstrated that External Qi of Yan Xin Qigong (YXQ-EQ) exerted potent cytotoxic effect towards SCLC cell line NCI-H82 via induction of apoptosis. Global gene expression profiling identified 39 genes whose expression was altered by YXQ-EQ in NCI-82 cells. Among them, semi-quantitative RT-PCR and real-time qPCR analyses confirmed that the gene expression levels of apoptotic proteins death-associated protein kinase 2 and cell death-inducing DFFA-like effector b were upregulated, whereas that of oncoproteins DEK and MYCL1, cell migration-promoting proteins CD24 and integrin-alpha 9, and glycolytic enzyme aldolase A were downregulated. These findings suggest that YXQ-EQ may exert anticancer effect through modulating gene expression in a way that facilitates cancer cell apoptosis while represses proliferation, metastasis, and glucose metabolism.

Erroneous augmentation of multiplex assay measurements in patients with rheumatoid arthritis due to heterophilic binding by serum rheumatoid factor.

OBJECTIVE: Serum rheumatoid factor (RF) and other heterophilic antibodies potentially interfere with antibody-based immunoassays by nonspecifically binding detection reagents. The purpose of this study was to assess whether these factors confound multiplex-based immunoassays, which are used with increasing frequency to measure cytokine and chemokine analytes in patients with rheumatoid arthritis (RA). METHODS: We performed multiplex immunoassays using different platforms to measure analyte concentrations in RA patient samples. Samples were depleted of RF by column-based affinity absorption or were exposed to agents that block heterophilic binding activity. RESULTS: In RA patients with high-titer RF, 69% of analytes demonstrated at least a 2-fold stronger multiplex signal in non-RF-depleted samples as compared to RF-depleted samples. This degree of erroneous signal amplification was less frequent in low-titer RF samples (17% of analytes; P < 0.0000001). Signal amplification by heterophilic antibodies was blocked effectively by HeteroBlock (≥ 150 µg/ml). In 35 RA patients, multiplex signals for 14 of 22 analytes were amplified erroneously in unblocked samples as compared to blocked samples (some >100-fold), but only in patients with high-titer RF (P < 0.002). Two other blocking agents, heterophilic blocking reagent and immunoglobulin-inhibiting reagent, also blocked heterophilic activity. CONCLUSION: All multiplex protein detection platforms we tested exhibited significant confounding by RF or other heterophilic antibodies. These findings have broad-reaching implications in the acquisition and interpretation of data derived from multiplex immunoassay testing of RA patient serum and possibly also in other conditions in which RF or other heterophilic antibodies may be present. Several available blocking agents effectively suppressed this erroneous signal amplification in the multiplex platforms tested.