Caracterización del uso de tofacitinib como tratamiento para COVID-19 / si

Objetivo: El propósito principal de este estudio es caracterizar y comparar la población que recibió tofacitinib con aquella que no fue tratada con este fármaco para la COVID-19 en la Clínica Unión Médica del Norte, durante el año 2020. Métodos: Se realizó un estudio de tipo observacional, retrospectivo transversal de tipo exploratorio y de fuente secundaria. Se analizaron las características de los participantes y su tratamiento en relación con los parámetros de laboratorio y las características clínicas. Resultados: Se incluyeron 507 pacientes ingresados en la unidad de COVID-19 de la Clínica Unión Médica del Norte. Se determinó que las defunciones fueron menores en el grupo que se medicó con tofacitinib (6,45%) en comparación con el grupo que no utilizó dicho fármaco. Asimismo, los medicados con esta terapia ameritaron en menos proporción soporte ventilatorio, sin embargo, hubo más proporción de ingresos a la Unidad de Cuidados Intensivos. Además, se identificó una reducción mayor en la glucemia en aquellos pacientes medicados con tofacitinib, aunque mayores niveles de ferritina y dímero D. Conclusiones: El fármaco tofacitinib puede actuar de manera beneficiosa en relación con la mortalidad y la reducción del uso de ventilación mecánica. En adición, podría colaborar con la evolución de los pacientes. No obstante, nuestra investigación no es concluyente. Es necesario realizar futuras investigaciones confirmatorias de la eficacia de la terapia con tofacitinib para los pacientes con COVID-19.

Objective: The main purpose of this study is to characterize and compare the population that received tofacitinib with those that were not treated with the drug for COVID-19 at the Clínica Unión Médica del Norte, in 2020. Methods: An observational, retrospective, cross-sectional, exploratory, and secondary source study was conducted. A comparison was made between clinical and sociodemographic characteristics, laboratory results and their treatment option. Results: Five hundred and seven patients admitted to the COVID-19 unit of the Clínica Unión Médica del Norte were included. It was determined that lower death rates were registered in the group that received tofacitinib (6.45%) compared to the group that did not use the drug. Likewise, those receiving this therapy required less mechanical ventilation, however, a higher proportion of these patients were admitted to the Intensive Care Unit. In addition, a greater reduction in glycaemia was identified in the patients receiving tofacitinib, but they had higher levels of ferritin and D-dimer. Conclusions: Tofacitinib may be beneficial in terms of mortality rates and reduction in the use of mechanical ventilation. Furthermore, it is promising with respect to positive patient progression. However, our research is not conclusive. Future confirmatory research is needed on the efficacy of tofacitinib therapy for COVID-19 patients.

Detection of Wheat Lipid Transfer Protein (Tri a 14) Sensitization: Comparison between Currently Available Diagnostic Tools.

BACKGROUND: Wheat lipid transfer protein (LTP; Tri a 14) and ω5-gliadin have been described as major allergens in wheat allergy (WA) and relevant in wheat-induced anaphylaxis, frequently associated with cofactors. OBJECTIVE: The objective of this study was to compare tools currently available in routine diagnosis to detect Tri a 14 sensitization, its clinical relevance, and cosensitization to ω5-gliadin and other LTPs. METHODS: One hundred eighteen adults sensitized to rTri a 14 by ImmunoCAP® (cutoff ≥0.1 kUA/L) identified among 210 LTP allergic patients were included. We evaluated (1) wheat skin prick test (SPT), (2) specific IgE (sIgE) to wheat, rTri a 14, rTri a 19, peach, apple, walnut, hazelnut, and peanut LTPs using ImmunoCAP® and microarray ImmunoCAP®ISAC (cutoff ≥0.3I SU), and (3) wheat-related symptoms. RESULTS: Wheat SPT and sIgE were positive in 31% and 85% of subjects, respectively. rTri a 14 by microarray was detected in 25%. Eight percent showed cosensitization to ω5-gliadin. Thirty percent referred symptoms (gastrointestinal [13%], urticaria [11%], and anaphylaxis [8%]). Cofactors (45%) were significantly associated with systemic reactions. CONCLUSION: WA due to Tri a 14 is frequently related with systemic reactions and because are frequently related to cofactors, the culprit may not be suspected. Together with the poor performance to identify Tri a 14 sensitization of the current routine diagnostic tools based on the analysis of whole wheat extract, such as wheat SPT or sIgE, there is a high risk that WA may be overlooked. Thus, when WA is suspected, sIgE Tri a 14 assessment is recommended, together with wheat and ω5-gliadin, preferably in the singleplex format, and carefully evaluated considering ≥0.1 kUA/L as a cutoff.

Mutation in KARS: A novel mechanism for severe anaphylaxis.

BACKGROUND: Anaphylaxis is a severe allergic reaction that can be lethal if not treated adequately. The underlying molecular mechanisms responsible for the severity are mostly unknown. OBJECTIVE: This study is based on a clinical case of a patient with extremely severe anaphylaxis to paper wasp venom. This patient has a mutation in the KARS gene, which encodes lysyl-tRNA synthetase (LysRS), a moonlight protein with a canonical function in protein synthesis and a noncanonical function in antigen dependent-FcεRI activation in mast cells. In this study, the objective was to characterize the mutation at the molecular level. METHODS: Analysis of the KARS mutation was carried out using biochemical and functional approaches, cell transfection, Western blot, confocal microscopy, cell degranulation, prostaglandin D2 secretion, and proteases gene transcription. Structural analysis using molecular dynamics simulations and well-tempered metadynamics was also performed. RESULTS: The mutation found, P542R (proline was replaced by arginine at aminoacid 542), affects the location of the protein as we show in biochemical and structural analyses. The mutation resembles active LysRS and causes a constitutive activation of the microphthalmia transcription factor, which is involved in critical mast cell functions such as synthesis of mediators and granule biogenesis. Moreover, the structural analysis provides insights into how LysRS works in mast cell activation. CONCLUSIONS: A link between the aberrant LysRS-P542R function and mast cell-exacerbated activation with increase in proinflammatory mediator release after antigen-IgE-dependent response could be established.

Artificial Intelligence and Machine Learning in Radiology: Opportunities, Challenges, Pitfalls, and Criteria for Success.

Worldwide interest in artificial intelligence (AI) applications, including imaging, is high and growing rapidly, fueled by availability of large datasets ("big data"), substantial advances in computing power, and new deep-learning algorithms. Apart from developing new AI methods per se, there are many opportunities and challenges for the imaging community, including the development of a common nomenclature, better ways to share image data, and standards for validating AI program use across different imaging platforms and patient populations. AI surveillance programs may help radiologists prioritize work lists by identifying suspicious or positive cases for early review. AI programs can be used to extract "radiomic" information from images not discernible by visual inspection, potentially increasing the diagnostic and prognostic value derived from image datasets. Predictions have been made that suggest AI will put radiologists out of business. This issue has been overstated, and it is much more likely that radiologists will beneficially incorporate AI methods into their practices. Current limitations in availability of technical expertise and even computing power will be resolved over time and can also be addressed by remote access solutions. Success for AI in imaging will be measured by value created: increased diagnostic certainty, faster turnaround, better outcomes for patients, and better quality of work life for radiologists. AI offers a new and promising set of methods for analyzing image data. Radiologists will explore these new pathways and are likely to play a leading role in medical applications of AI.

Watershed-scale assessment of background concentrations and guidance values for heavy metals in soils from a semiarid and coastal zone of Brazil.

Determining heavy metal background concentrations in soils is fundamental in order to support the monitoring of potentially contaminated areas. This is particularly important to areas submitted to high environmental impact where an intensive and local monitoring is required. To this end, the aim of this study was to establish background concentrations and quality reference values (QRVs) for the heavy metals Cd, Cr, Cu, Fe, Mn, Ni, Pb, Zn, As, and Hg in an environmentally impacted watershed from Brazil. Geochemical associations among Fe, Mn, and trace elements were also assessed to provide an alternative tool for establishing background concentrations. A total of one hundred and four samples comprised twenty-six composite soil samples from areas of native forest or minimal anthropic influence. Samples were digested (USEPA method 3051A), and the metals were determined by ICP-OES, except for As and Hg measured by atomic absorption spectrophotometer. Background concentrations of heavy metals in soils had the following decreasing order: Fe > Mn > Zn > Cr > Pb > Ni > Cu > As > Cd > Hg. These values were usually lower than those observed in the international and national literature. The QRVs for Ipojuca watershed followed the order (mg kg(-1)) Fe (13,020.40) > Mn (91.80) > Zn (30.12) > Cr (15.00) > Pb (13.12) > Cu (3.53) > Ni (3.30) > As (0.51) > Cd (0.08) > Hg (0.04). Significant correlation among Fe, Mn, and heavy metals shows that solubilization by the method 3051A provides a reasonable estimate for predicting background concentrations for Cd, Cr, and Cu as well as Zn, Cr, Cu, and Ni.

Ischemic colitis: spectrum of CT findings, sites of involvement and severity.

To summarize the frequency of findings on IV contrast, enhanced computer tomography (CT) in 335 patients with pathologically proven ischemic colitis (IC) determine the most frequent locations and patterns of involvement and establish the correlation of these findings with the severity of IC. 231 patients were excluded for not having a concomitant CT or for having underlying comorbidities. 104 cases were analyzed. Scans were evaluated for abnormal wall enhancement (AE), bowel wall thickening (BWT), bowel dilatation (DIL), mesenteric fat stranding (FS), venous engorgement (VE), pericolonic free fluid (FF), and pneumatosis (PN) and portomesenteric venous gas. Segmental versus pancolonic involvement was noted. Severity was determined by histopathology criteria. Data obtained are as follows: female to male incidence, 69 % (70) vs. 31 % (34); average age, 64.5; and positive CT, 102/104 (98.1 %). The most frequent findings include FS (88 %), BWT (88 %), and AE (82 %) regardless of severity of involvement. Statistically significant increased risk ratio and likelihood of severe ischemia for PN, DIL, and FF individually. BWT, DIL, FS, FF, VE, and PN together have a probability for severe IC of 91.8 %. A correlation between fewer findings and milder IC was found (R (2) = 0.6771). The most frequently involved segments: descending (64 %) and sigmoid colon (54 %). Splenic flexure (SF) was infrequently involved (n = 8, 7.84 %). Females had two times higher incidence of IC. The most frequent CT findings in IC are FS, BWT, and AE regardless of the severity. PN is suggestive of severe IC. Segmental involvement is the predominant pattern. The distal colon is more frequently involved. SF contrary to the conventional literature is not disproportionately involved in IC.