Anaphylaxis: Clinical patterns, mediator release, and severity Brown, Simon G.A., MBBS, PhD, FACEM; Stone, Shelley F., PhD; Fatovich, Daniel M., MBBS, FACEM, PhD ...
Journal of allergy and clinical immunology,
11/2013, Letnik:
132, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Background Prospective human studies of anaphylaxis and its mechanisms have been limited, with few severe cases or examining only 1 or 2 mediators. Objectives We wanted to define the clinical ...patterns of anaphylaxis and relationships between mediators and severity. Methods Data were collected during treatment and before discharge. Serial blood samples were taken for assays of mast cell tryptase, histamine, anaphylatoxins (C3a, C4a, C5a), cytokines (IL-2, IL-6, IL-10), soluble tumor necrosis factor receptor I, and platelet activating factor acetyl hydrolase. Principal component analysis defined mediator patterns, and logistic regression identified risk factors and mediator patterns associated with reaction severity and delayed reactions. Results Of 412 reactions in 402 people, 315 met the definition for anaphylaxis by the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network. Of 97 severe reactions 45 (46%) were hypotensive, 23 (24%) were hypoxemic, and 29 (30%) were mixed. One patient died. Severe reactions were associated with older age, pre-existing lung disease, and drug causation. Delayed deteriorations treated with epinephrine occurred in 29 of 315 anaphylaxis cases (9.2%) and were more common after hypotensive reactions and with pre-existing lung disease. Twenty-two of the 29 delayed deteriorations (76%) occurred within 4 hours of initial epinephrine treatment. Of the remaining 7 cases, 2 were severe and occurred after initially severe reactions, within 10 hours. All mediators were associated with severity, and 1 group (mast cell tryptase, histamine, IL-6, IL-10, and tumor necrosis factor receptor I) was also associated with delayed deteriorations. Low platelet activating factor acetyl hydrolase activity was associated with severe reactions. Conclusion The results suggest that multiple inflammatory pathways drive reaction severity and support recommendations for safe observation periods after initial treatment.
Among patients with large colorectal sessile polyps or laterally spreading lesions, it is important to identify those at risk for submucosal invasive cancer (SMIC). Lesions with overt endoscopic ...evidence of SMIC are referred for surgery, although those without these features might still contain SMIC that is not visible on endoscopic inspection (covert SMIC). Lesions with a high covert SMIC risk might be better suited for endoscopic submucosal dissection than for endoscopic mucosal resection (EMR). We analyzed a group of patients with large colon lesions to identify factors associated with SMIC, and examined lesions without overt endoscopic high-risk signs to determine factors associated with covert SMIC.
We performed a prospective cohort study of consecutive patients referred for EMR of large sessile or flat colorectal polyps or laterally spreading lesions (≥20 mm) at academic hospitals in Australia from September 2008 through September 2016. We collected data on patient and lesion characteristics, outcomes of procedures, and histology findings. We excluded serrated lesions from the analysis of covert SMIC due to their distinct phenotype and biologic features.
We analyzed 2277 lesions (mean size, 36.9 mm) from 2106 patients (mean age, 67.7 years; 53.2% male). SMIC was evident in 171 lesions (7.6%). Factors associated with SMIC included Kudo pit pattern V, a depressed component (0–IIc), rectosigmoid location, 0–Is or 0–IIa+Is Paris classification, non-granular surface morphology, and increasing size. After exclusion of lesions that were obviously SMIC or serrated, factors associated with covert SMIC were rectosigmoid location (odds ratio, 1.87; P = .01), combined Paris classification, surface morphology (odds ratios, 3.96−22.5), and increasing size (odds ratio, 1.16/10 mm; P = .012).
In a prospective study of 2106 patients who underwent EMR for large sessile or flat colorectal polyps or laterally spreading lesions, we associated rectosigmoid location, combined Paris classification and surface morphology, and increasing size with increased risk for covert malignancy. Rectosigmoid 0–Is and 0–IIa+Is non-granular lesions have a high risk for malignancy, whereas proximally located 0–Is or 0–IIa granular lesions have a low risk. These findings can be used to inform decisions on which patients should undergo endoscopic submucosal dissection, EMR, or surgery. ClinicalTrials.gov, Number: NCT02000141.
Scaling relationships between skeletal dimensions and body mass in extant birds are often used to estimate body mass in fossil crown-group birds, as well as in stem-group avialans. However, useful ...statistical measurements for constraining the precision and accuracy of fossil mass estimates are rarely provided, which prevents the quantification of robust upper and lower bound body mass estimates for fossils. Here, we generate thirteen body mass correlations and associated measures of statistical robustness using a sample of 863 extant flying birds. By providing robust body mass regressions with upper- and lower-bound prediction intervals for individual skeletal elements, we address the longstanding problem of body mass estimation for highly fragmentary fossil birds. We demonstrate that the most precise proxy for estimating body mass in the overall dataset, measured both as coefficient determination of ordinary least squares regression and percent prediction error, is the maximum diameter of the coracoid's humeral articulation facet (the glenoid). We further demonstrate that this result is consistent among the majority of investigated avian orders (10 out of 18). As a result, we suggest that, in the majority of cases, this proxy may provide the most accurate estimates of body mass for volant fossil birds. Additionally, by presenting statistical measurements of body mass prediction error for thirteen different body mass regressions, this study provides a much-needed quantitative framework for the accurate estimation of body mass and associated ecological correlates in fossil birds. The application of these regressions will enhance the precision and robustness of many mass-based inferences in future paleornithological studies.
Existing grading systems for acute systemic hypersensitivity reactions vary considerably, have a number of deficiencies, and lack a consistent definition of anaphylaxis.
The aims of this study were ...to develop a simple grading system and definition of anaphylaxis and to identify predictors of reaction severity.
Case records from 1149 systemic hypersensitivity reactions presenting to an emergency department were analyzed retrospectively. Logistic regression analyses of the associations between individual reaction features and hypotension and hypoxia were used to construct a grading system. Epinephrine use, etiology, age, sex, comorbidities, and concurrent medications were then assessed for their association with reaction grade.
Confusion, collapse, unconsciousness, and incontinence were strongly associated with hypotension and hypoxia and were used to define severe reactions. Diaphoresis, vomiting, presyncope, dyspnea, stridor, wheeze, chest/throat tightness, nausea, vomiting, and abdominal pain had weaker, albeit significant, associations and were used to define moderate reactions. Reactions limited to the skin (urticaria, erythema, and angioedema) were defined as mild. These grades correlated well with epinephrine usage. Older age, insect venom, and iatrogenic causes were independent predictors of severity. Preexisting lung disease was associated with an increased risk of hypoxia.
This simple grading system has potential value for defining reaction severity in clinical practice and research settings. The moderate and severe grades provide a workable definition of anaphylaxis. Age, reaction precipitant, and preexisting lung disease appear to be the major determinants of reaction severity.
We describe the memristive properties of cluster-assembled gold films. We show that resistive switching is observed in pure metallic nanostructured films at room temperature and atmospheric pressure, ...in response to applied voltage inputs. In particular, we observe resistance changes up to 400% and archetypal switching events that have remarkable symmetry with the applied voltage. We associated this symmetry with 'potentiation' and 'anti-potentiation' processes involving the activation of synapses and of pathways comprising multiple synapses. The stability and reproducibility of the resistance switching, which lasted over many hours, make these devices ideal test-beds for exploration of the basic mechanisms of the switching processes, and allow convenient fabrication of devices that may have neuromorphic properties.
CRISPR-Cas systems provide bacteria with adaptive immunity against foreign nucleic acids by acquiring short, invader-derived sequences called spacers. Here, we use high-throughput sequencing to ...analyse millions of spacer acquisition events in wild-type populations of Pectobacterium atrosepticum. Plasmids not previously encountered, or plasmids that had escaped CRISPR-Cas targeting via point mutation, are used to provoke naive or primed spacer acquisition, respectively. The origin, location and order of spacer acquisition show that spacer selection through priming initiates near the site of CRISPR-Cas recognition (the protospacer), but on the displaced strand, and is consistent with 3'-5' translocation of the Cas1:Cas2-3 acquisition machinery. Newly acquired spacers determine the location and strand specificity of subsequent spacers and demonstrate that interference-driven spacer acquisition ('targeted acquisition') is a major contributor to adaptation in type I-F CRISPR-Cas systems. Finally, we show that acquisition of self-targeting spacers is occurring at a constant rate in wild-type cells and can be triggered by foreign DNA with similarity to the bacterial chromosome.
Wide-field endoscopic mucosal resection (WF-EMR) of large sessile colonic polyps is a safe and cost-effective outpatient treatment. Bleeding is the main complication. Few studies have examined risk ...factors for bleeding during the procedure (intraprocedural bleeding IPB) or after it (clinically significant post-endoscopic bleeding CSPEB). We investigated factors associated with IPB and CSPEB in a large prospective study.
We analyzed data from WF-EMRs of sessile colorectal polyps ≥ 20 mm in size (mean size, 35.5 mm), which were performed on 1172 patients (mean age, 67.8 years) from June 2008-March 2013 at 7 tertiary hospitals as part of the Australian Colonic Endoscopic Resection Study. Data were collected on characteristics of patients and lesions, along with outcomes of procedures and clinical and histologic analyses. Independent predictors of IPB and CSPEB were identified by multiple logistic regression analysis.
Of the patients studied, 133 (11.3%) had IPB. Independent predictors included increasing lesion size (odds ratio, 1.24/10 mm; P < .001), Paris endoscopic classification of 0-IIa + Is (odds ratio, 2.12; P = .004), tubulovillous or villous histology (odds ratio, 1.84; P = .007), and study institutions that performed the procedure on fewer than 75 patients (odds ratio, 3.78; P < .001). All IPB was successfully controlled endoscopically. IPB prolonged procedures and was associated with early recurrence (relative risk, 1.68; P = .011). Seventy-three patients (6.2%) had CSPEB. On multivariable analysis, CSPEB was associated with proximal colon location (odds ratio, 3.72; P < .001), use of an electrosurgical current not controlled by a microprocessor (odds ratio, 2.03; P = .038), and IPB (odds ratio, 2.16; P = .016). Lesion size and comorbidities did not predict CSPEB.
In a prospective study of patients undergoing WF-EMR of large sessile colonic polyps, IPB is associated with larger lesions, lesion histology, and Paris endoscopic classification of type 0-IIa + Is. IPB prolongs the duration of the procedure, is a marker for recurrence, and is associated with CSPEB. CSPEB occurs most frequently in the proximal colon and less when current is controlled by a microprocessor.
Clarke and Beck (C&B) assume that approximate number system (ANS) representations should be assigned referents from our scientific ontology. However, many representations, both in perception and ...cognition, do not straightforwardly refer to such entities. If we reject C&B's assumption, many possible contents for ANS representations besides number are compatible with the evidence C&B cite.
To identify biomarkers which distinguish severe sepsis/septic shock from uncomplicated sepsis in the Emergency Department (ED).
Patients with sepsis underwent serial blood sampling, including arrival ...in the ED and up to three subsequent time points over the first 24 hours. Messenger RNA (mRNA) levels of 13 genes representing arms of the innate immune response, organ dysfunction or shock were measured in peripheral blood leucocytes using quantitative PCR, and compared with healthy controls. Serum protein concentrations of targets differentially expressed between uncomplicated sepsis and severe sepsis/septic shock were then measured at each time point and compared between the two patient groups.
Of 27 participants (median age 66 years, (IQR 35, 78)), 10 had uncomplicated sepsis and 17 had sepsis with organ failure (14 septic shock; 3 had other sepsis-related organ failures). At the time of first sample collection in the ED, gene expression of Interleukin (IL)-10 and Neutrophil Gelatinase Associated Lipocalin (NGAL) were significantly higher in severe sepsis than uncomplicated sepsis. Expression did not significantly change over time for any target gene. Serum concentrations of IL-6, IL-8, IL-10, NGAL and Resistin were significantly higher in severe sepsis than uncomplicated sepsis at the time of first sample collection in the ED, but only IL-8, NGAL and Resistin were consistently higher in severe sepsis compared to uncomplicated sepsis at all time points up to 24 h after presentation.
These mediators, produced by both damaged tissues and circulating leukocytes, may have important roles in the development of severe sepsis. Further work will determine whether they have any value, in addition to clinical risk parameters, for the early identification of patients that will subsequently deteriorate and/or have a higher risk of death.
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