The challenge of delabeling amoxicillin allergy is an important issue for patients and clinicians, especially when anaphylaxis is reported. A recent study has proposed a clinical decision rule, ...PEN-FAST, to identify low-risk penicillin allergies.
To validate the PEN-FAST clinical decision rule in a population with high risk of suspected immediate amoxicillin allergy and to identify clinical predictive factors of amoxicillin immediate hypersensitivity.
We retrospectively analyzed medical records of patients with a suspected immediate amoxicillin allergy who carried out an allergologic evaluation by a specialist in the Allergy Unit of Strasbourg University Hospital from 2015 to 2020.
A total of 142 adult patients (88 women 62.0%; median age, 52 interquartile range, 40.3-62.0 years) were analyzed. Most of them reported anaphylaxis (68.8%). Internal validation of PEN-FAST score revealed a good discrimination with area under the curve of 0.86 (95% confidence interval, 0.79-0.92). A cutoff of less than 3 points for PEN-FAST was used to classify 29 from 142 patients at low risk of allergy, of whom only 2 (6.9%) received positive results of allergy testing. The negative predictive value for successful delabeling was 0.93 (95% confidence interval, 0.77-0.99). Predictive clinical features for immediate amoxicillin hypersensitivity were time since reaction (P < .001), time elapsed between drug intake and first symptom (P < .001), severity grade reaction (P < .001), and treatment or hospitalization required (P < .001).
PEN-FAST has been validated to identify low-risk penicillin allergies in our European cohort of patients mainly reporting anaphylaxis. This is the first reported external validation of a penicillin allergy clinical decision rule internationally.
Quasi-2D nanoporous gold ultra-thin films have been elaborated and investigated by specific surface approaches. Three different microscopy techniques (Transmission Electron Microscopy (TEM), Scanning ...Electron Microscopy (SEM), and Atomic Force Microscopy (AFM)) have been used for the characterizations. A careful statistical analysis of experimental images has been done, thanks to the development of a dedicated image analysis software. It reveals that the inhomogeneous gold nanomesh at low length scale becomes homogeneous at a length scale larger than the biggest pores size of about 2 mu m, with a constant opacity reaching 35%. At such a scale, the ligaments present an average diameter of 20 nm and an average length of 70 nm. While TEM and SEM present similar results, AFM overestimates the geometric characteristics due to tip convolution effect. However, the topology of the nanomesh is not affected. This study also reveals pores with a much larger size in the quasi 2D nanoporous ultra-thin film than in its bulk counterpart for similar ligaments diameters, which could play an important role in its mechanical properties.
•Support vector machines offer good classification results for pathology reports.•Machine learning can improve cancer registry registration process.•Simple regular expression can extract data from ...French pathology report.
Cancer registries are collections of curated data about malignant tumor diseases. The amount of data processed by cancer registries increases every year, making manual registration more and more tedious.
We sought to develop an automatic analysis pipeline that would be able to identify and preprocess registry input for incident prostate adenocarcinomas in a French regional cancer registry.
Notifications from different sources submitted to the Bas-Rhin cancer registry were used here: pathology data and, ICD 10 diagnosis codes from hospital discharge data and healthcare insurance data. We trained a Support Vector Machine model (machine learning) to predict whether patient’s data must be considered or not as a prostate adenocarcinoma incident case that should therefore be registered. The final registration of all identified cases was manually confirmed by a specialized technician. Text mining tools (regular expressions) were used to extract clinical and biological data from non-structured pathology reports.
We performed two successive analyses. First, we used 982 cases manually labeled by registrars from the 2014 dataset to predict the registration of 785 cases submitted in 2015. Then, we repeated the procedure using the 2089 cases labeled by registrars from the 2014 and 2015 datasets to predict the registration of 926 cases submitted in the 2016 data. The algorithm identified 663 cases of prostate adenocarcinoma in 2015, and 610 in 2016. From these findings, 663 and 531 cases were respectively added to the registry; and 641 and 512 cases were confirmed by the specialized technician. This registration process has achieved a precision level above 96 %. The algorithm obtained an overall precision of 99 % (99.5 % in 2015 and 98.5 % in 2016) and a recall of 97 % (97.8 % in 2015 and 96.9 % in 2016). When the information was found in pathology report, text mining was more than 90 % accuracy for major indicators: PSA test, Gleason score, and incidence date). For both PSA and tumor side, information was not detected in the majority of cases.”
Machine learning was able to identify new cases of prostate cancer, and text mining was able to prefill the data about incident cases. Machine-learning-based automation of the registration process could reduce delays in data production and allow investigators to devote more time to complex tasks and analysis.
This prospective study aimed to compare the complication rates and clinical outcomes of propensity-matched patients who received fast-track total knee arthroplasty (FT TKA) in outpatient versus ...inpatient settings.
Patients (n = 629) who received FT TKA at various outpatient (n = 176) and inpatient (n = 462) surgery rates were prospectively followed until 90 days after surgery. The decision between inpatient versus outpatient FT TKA was made on a case-by-case basis, depending on consultation between the surgeon and patient. Complications were collected to distinguish between intraoperative complications, complications with no readmission, complications with readmission, and complications with reoperation. Propensity scores based on age, sex, body mass index, and the American Society of Anesthesiologists score were used to match outpatient to inpatient FT TKA. A cumulative incidence function was computed by taking the time to diagnose any postoperative complication in the first 90 days as the end point.
Propensity score matching (1:2 ratio) for comparison resulted in 173 outpatient FT TKAs and 316 inpatient FT TKAs. No significant differences were observed between outpatient versus inpatient FT TKA for intraoperative complication rates (2% in both groups). At 90-day follow-up, no significant differences were observed between outpatient versus inpatient FT TKA for total complications with no readmission (8.0 versus 7.9%), complications with readmission but no reoperation (1.1 versus 0.6%), and complications with reoperation (4.0 versus 4.4%). A comparison of postoperative complication diagnosis time using the cumulative incidence function revealed no significant differences between outpatient versus inpatient FT TKA.
The present study revealed that there were no differences in 90-day postoperative complication rates between outpatient and inpatient FT TKA and that there were also no differences in rates of intraoperative complications, readmissions, or reoperations. These findings may encourage hesitant surgeons to move toward outpatient TKA pathways, as there is no greater risk of early postoperative complications that could be more difficult to manage after discharge.
Level II.
We report an unexpected characteristic of dislocation cores in silicon. Using first-principles calculations, we show that all of the stable core configurations for a nondissociated 60 degrees ...dislocation are sessile. The only glissile configuration, previously obtained by nucleation from surfaces, surprisingly corresponds to an unstable core. As a result, the 60 degrees dislocation motion is solely driven by stress, with no thermal activation. We predict that this original feature could be relevant in situations for which large stresses occur, such as mechanical deformation at room temperature. Our work also suggests that postmortem observations of stable dislocations could be misleading and that mobile unstable dislocation cores should be taken into account in theoretical investigations.
Because of the high risk of thrombotic complications (TCs) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although ...arguments in favor of this strategy are inconsistent.
What is the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC?
All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight.
Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%). Pulmonary embolism accounted for 52% of the recorded TCs. High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75).
High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill patients with COVID-19 without an increased risk of hemorrhage. Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results.
ClinicalTrials.gov; No.: NCT04405869; URL: www.clinicaltrials.gov
Nuclear hormone receptors (NHRs) control numerous physiological processes through the regulation of gene expression. The present study provides a structural basis for understanding the role of DNA in ...the spatial organization of NHR heterodimers in complexes with coactivators such as Med1 and SRC-1. We have used SAXS, SANS and FRET to determine the solution structures of three heterodimer NHR complexes (RXR-RAR, PPAR-RXR and RXR-VDR) coupled with the NHR interacting domains of coactivators bound to their cognate direct repeat elements. The structures show an extended asymmetric shape and point to the important role played by the hinge domains in establishing and maintaining the integrity of the structures. The results reveal two additional features: the conserved position of the ligand-binding domains at the 5' ends of the target DNAs and the binding of only one coactivator molecule per heterodimer, to RXR's partner.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
High‐molecular‐weight (HMW) proteins and low‐molecular‐weight (LMW) chemicals can cause occupational asthma (OA) although few studies have thoroughly compared the clinical, physiological, ...and inflammatory patterns associated with these different types of agents. The aim of this study was to determine whether OA induced by HMW and LMW agents shows distinct phenotypic profiles.
Methods
Clinical and functional characteristics, and markers of airway inflammation were analyzed in an international, multicenter, retrospective cohort of subjects with OA ascertained by a positive inhalation challenge response to HMW (n = 544) and LMW (n = 635) agents.
Results
Multivariate logistic regression analysis showed significant associations between OA caused by HMW agents and work‐related rhinitis (OR 95% CI: 4.79 3.28‐7.12), conjunctivitis (2.13 1.52‐2.98), atopy (1.49 1.09‐2.05), and early asthmatic reactions (2.86 1.98‐4.16). By contrast, OA due to LMW agents was associated with chest tightness at work (2.22 1.59‐3.03), daily sputum (1.69 1.19‐2.38), and late asthmatic reactions (1.52 1.09‐2.08). Furthermore, OA caused by HMW agents showed a higher risk of airflow limitation (1.76 1.07‐2.91), whereas OA due to LMW agents exhibited a higher risk of severe exacerbations (1.32 1.01‐1.69). There were no differences between the two types of agents in the baseline sputum inflammatory profiles, but OA caused by HMW agents showed higher baseline blood eosinophilia and a greater postchallenge increase in fractional nitric oxide.
Conclusion
This large cohort study describes distinct phenotypic profiles in OA caused by HMW and LMW agents. There is a need to further explore differences in underlying pathophysiological pathways and outcome after environmental interventions.
This large European, multicenter, retrospective cohort of subjects with occupational asthma (n = 1167) documented by a positive specific inhalation challenge highlighted clinical phenotypic differences between high‐ and low‐molecular‐weight causal agents. High‐molecular‐weight agents were associated with a higher likelihood of atopy, work‐related rhinoconjunctivitis, baseline airflow limitation, early asthmatic reactions, and higher levels of FeNO. Occupational asthma due to low‐molecular‐weight agents was associated with a higher rate of chest tightness and sputum at work, a higher risk of severe asthma exacerbations, and late asthmatic reactions.
Understanding the origin of the brittle to ductile transition at low scale in Si requires the characterization of the elementary mechanisms governing crack formation or dislocation nucleation. By ...molecular dynamics simulations, we have investigated the role of three surface states of silicon nanowires (NWs), fresh cut, reconstructed by annealing at 300 K and amorphized, for the activation of plastic mechanisms under tensile and compressive strains. We show that the onset of crack formation identified as wedge‐shaped defect on the surface was only observed in fresh‐cut NWs in tension. These NWs present high yield strain due to the high symmetry of the surface and the absence of surface defects favoring dislocation nucleation as for the other surface states. This result seems to confirm that the crack formation in nanostructures could be linked to dislocations interactions on intersecting glide planes as experimentally observed rather than direct crack opening.
Although bulk Si is brittle below 600–700 K, the compression of Si nanopillars at room temperature shows a change in the mechanical response from brittleness to ductility for small pillar diameters. Identifying the relevant parameters governing the size‐dependent brittle‐to‐ductile transition and understanding the underlying mechanisms are key points to further develop the MEMS and NEMS technology or to prevent the failure of microelectronic components based on strained silicon technology. Godet et al. perform atomistic simulations combining static relaxation and molecular dynamics, on nanowires submitted to compressive and tensile strains. The authors compare the yield strain of nanowires with different surface states and correlate it to surface defects and to the formation of dislocations or cracks.
The Pr55 Gag of human immunodeficiency virus type 1 orchestrates viral particle assembly in producer cells, which requires the genomic RNA and a lipid membrane as scaffolding platforms. The ...nucleocapsid (NC) domain with its two invariant CCHC zinc fingers flanked by unfolded basic sequences is thought to direct genomic RNA selection, dimerization and packaging during virus assembly. To further investigate the role of NC domain, we analyzed the assembly of Gag with deletions in the NC domain in parallel with that of wild-type Gag using fluorescence lifetime imaging microscopy combined with Förster resonance energy transfer in HeLa cells. We found that, upon binding to nucleic acids, the NC domain promotes the formation of compact Gag oligomers in the cytoplasm. Moreover, the intracellular distribution of the population of oligomers further suggests that oligomers progressively assemble during their trafficking toward the plasma membrane (PM), but with no dramatic changes in their compact arrangement. This ultimately results in the accumulation at the PM of closely packed Gag oligomers that likely arrange in hexameric lattices, as revealed by the perfect match between the experimental Förster resonance energy transfer value and the one calculated from the structural model of Gag in immature viruses. The distal finger and flanking basic sequences, but not the proximal finger, appear to be essential for Gag oligomer compaction and membrane binding. Moreover, the full NC domain was found to be instrumental in the kinetics of Gag oligomerization and intracellular trafficking. These findings further highlight the key roles played by the NC domain in virus assembly.
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•Human immunodeficiency virus type 1 Gag oligomerization starts in the cytoplasm and Gag progressively accumulates at the PM.•Zinc fingers of the NC domain of Gag are required for the compaction of Gag oligomers.•Zinc fingers are instrumental for the spatiotemporal distribution of Gag in cells.
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