Artículos de revista (CUN)
Permanent URI for this collectionhttps://hdl.handle.net/10171/70263
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- Double subcutaneous island pedicle flap for reconstruction of large upper and central chin defects(John Wiley & Sons, 2024) Gómez Arias, P. (Pedro); Salido-Vallejo, R. (Rafael); Antoñanzas-Perez, J. (Javier); Aguado, L. (Leyre)Chin reconstruction poses a significant task for dermatologic surgeons due to its unique contour and shape, as well as the fact that it features the thickest skin on the face, resulting in typically poorer scarring in this area compared to other facial locations.There are numerous reconstructive options employed for the closure of oncological surgical defects in the chin region, ranging from advancement, transposition or rotation flaps to much more complex choices like free flaps. We present a case of a surgical defect in the midportion of the chin successfully reconstructed using a double island advancement flap.
- Proteomic and biological analysis of an in vitro human endothelial system in response to drug anaphylaxis(Frontiers, 2021) Oliva, T. (Tamara); Alvarez-Llamas, G. (Gloria); Goikoetxea-Lapresa, M.J. (María José); López, J.A. (Juan A.); Esteban, V. (Vanesa); Laguna, J.J. (José Julio); Martin-Lorenzo, M. (Marta); Betancor, D. (Diana); Yuste-Montalvo, A. (Alma); Pastor-Vargas, C. (Carlos); Fernandez-Bravo, S. (Sergio); Cuesta-Herranz, J. (Javier)Anaphylaxis is a life-threatening systemic hypersensitivity reaction. During anaphylaxis, mediator release by effector cells causes endothelial barrier breakdown, increasing vascular permeability and leakage of fluids, which may lead to tissue edema. Although endothelial cells (ECs) are key players in this context, scant attention has been paid to the molecular analysis of the vascular system, and further analyses of this cell type are necessary, especially in humans. The protein expression pattern of human microvascular ECs was analyzed in response to sera from anaphylactic patients (EC-anaphylaxis) and sera from non-allergic subjects (EC-control) after 2 hours of contact. Firstly, a differential quantitative proteomic analysis of the protein extracts was performed by mass spectrometry using an isobaric labeling method. Second, the coordinated behavior of the identified proteins was analyzed using systems biology analysis (SBA). The proteome of the EC-anaphylaxis system showed 7,707 proteins, of which 1,069 were found to be significantly altered between the EC-control and EC-anaphylaxis groups (p-value < 0.05). Among them, a subproteome of 47 proteins presented a high rate of change (|ΔZq| ≥ 3). This panel offers an endothelial snapshot of the anaphylactic reaction. Those proteins with the highest individual changes in abundance were hemoglobin subunits and structural support proteins. The interacting network analysis of this altered subproteome revealed that the coagulation and complement systems are the main biological processes altered in the EC-anaphylactic system. The comprehensive SBA resulted in 5,512 functional subcategories (biological processes), 57 of which were significantly altered between EC-control and EC-anaphylaxis. The complement system, once again, was observed as the main process altered in the EC system created with serum from anaphylactic patients. Findings of the current study further our understanding of the underlying pathophysiological mechanisms operating in anaphylactic reactions. New target proteins and relevant signaling pathways operating in the in vitro endothelial-serum system have been identified. Interestingly, our results offer a protein overview of the micro-EC-anaphylaxis environment. The relevance of the coagulation, fibrinolytic, contact and complement systems in human anaphylaxis is described. Additionally, the untargeted high-throughput analysis used here is a novel approach that reveals new pathways in the study of the endothelial niche in anaphylaxis.
- Mobile app/web platform for monitoring food oral immunotherapy in children: longitudinal clinical validation study(JMIR, 2024) López-de-Calle, M. (Marta); Sánchez-Fernández, S. (Sergio); Goikoetxea-Lapresa, M.J. (María José); Lasa, E.M. (Eva María); Cabrera-Freitag, P. (Paula); Terrados, S. (Soledad); Martínez-Molina, S. (Sara); Sola-Martínez, F.J. (Francisco Javier)Background: Milk and egg allergies significantly impact the quality of life, particularly in children. In this regard, food oral immunotherapy (OIT) has emerged as an effective treatment option; however, the occurrence of frequent adverse reactions poses a challenge, necessitating close monitoring during treatment. Objective: This study aims to evaluate the ability of a new mobile/web app called OITcontrol to monitor milk and egg OIT. Methods: Patients undergoing milk or egg OIT were recruited and divided into 2 groups: the active group used the OITcontrol app in conjunction with standard written monitoring methods, whereas the control group relied solely on written diaries. Investigators documented hospital doses, hospital reactions, and administered treatments on the website. Patients recorded their daily allergen home-dose intake, home reactions, and administered treatments using the app. The following variables were compared between both groups: number and severity of hospital and reported home reactions, patient's adhesion to the OITcontrol app or written diary or both in terms of daily home-dose intake and home reactions recording, and treatment and dose adjustment compliance at home in case of reaction. Results: Sixteen patients were assigned to be monitored using the OITcontrol app along with additional written methods (active group), while 14 patients relied solely on a written paper diary (control group). A similar distribution was observed in terms of sex, age, basal characteristics, allergen treated in OIT, premedication, and sensitization profile. Active patients reported a comparable number of hospital and home reactions compared with the control group. In terms of recording system usage, 13/16 (81%) active patients used the OITcontrol app, while 10/14 (71%) control patients relied on the written diary. Among active patients, 6/16 (38%) used both methods, and 1 active patient used only written methods. However, control patients recorded home reactions more frequently than active patients (P=.009). Among active patients, the app was the preferred method for recording reactions (59/86, 69%), compared with the written diary (15/86, 17%) or both methods (12/86, 14%; P<.001). Treatment compliance in home-recorded reactions was similar between both groups (P=.15). However, treatment indications after an adverse reaction were more frequently followed (P=.04) in reactions recorded solely in the app (36/59, 61%) than in the written diary (29/71, 41%) or both systems (4/12, 33%). Moreover, compliance with dose adjustments after a moderate-severe reaction in home-recorded reactions was higher in the active group than in the control group (P<.001). Home reactions recorded only in the app (16/19, 84%) were more likely to follow dose adjustments (P<.001) than those recorded in the written diary (3/20, 15%) or using both methods (2/3, 67%). Conclusions: The OITcontrol app appears to be a valuable tool for monitoring OIT treatment in children with food allergies. It proves to be a suitable method for recording daily home dose intakes and reactions, and it seems to enhance adherence to treatment indications following an adverse reaction as well as compliance with dose adjustments in home reactions. However, additional studies are necessary to comprehensively grasp the benefits and limitations of using the OITcontrol app in the management of OIT.
- Timing and duration of omalizumab response in patients with chronic idiopathic/spontaneous urticaria(Elsevier, 2016) Omachi, T.A. (Theodore A.); Zazzali, J.L. (James L.); Rosén, K. (Karin); Khalil, S. (Sam); Kaplan, A.P. (Allen .P); Trzaskoma, B. (Benjamin); Bernstein, J.A. (Jonathan A.); Raimundo, K. (Karina); Ferrer-Cardona, M. (Marta); Antonova, E. (Evgeniya)Background: Few data are available that describe response patterns in patients with chronic idiopathic urticaria (CIU)/chronic spontaneous urticaria (CSU) treated with omalizumab. Objective: We sought to describe response patterns by using data from the 3 pivotal omalizumab CIU/CSU trials. Methods: Every 4 weeks, randomized patients received dosing with placebo or 75, 150, or 300 mg of omalizumab (ASTERIA I: n = 318, 24 weeks; ASTERIA II: n = 322, 12 weeks) or placebo or 300 mg of omalizumab (GLACIAL: n = 335, 24 weeks). Response was defined as well-controlled urticaria (weekly Urticaria Activity Score [UAS7] ≤ 6) or complete response (UAS7 = 0). Results: Response rates were dose dependent and highest with 300 mg of omalizumab. Some patients responded early (before week 4). At week 12, a higher proportion of patients treated with 300 mg of omalizumab reported a UAS7 ≤ 6 (26.0% [75 mg of omalizumab], 40.0% [150 mg of omalizumab], 51.9% [300 mg of omalizumab], and 11.3% [placebo] for ASTERIA I; 26.8% [75 mg of omalizumab], 42.7% [150 mg of omalizumab], 65.8% [300 mg of omalizumab], and 19.0% [placebo] for ASTERIA II; and 52.4% [300 mg of omalizumab] and 12.0% [placebo] for GLACIAL) or a UAS7 = 0 (11.7% [75 mg of omalizumab], 15.0% [150 mg of omalizumab], 35.8% [300 mg of omalizumab], and 8.8% [placebo] for ASTERIA I; 15.9% [75 mg of omalizumab], 22.0% [150 mg of omalizumab], 44.3% [300 mg of omalizumab], and 5.1% [placebo] for ASTERIA II; and 33.7% [300 mg of omalizumab] and 4.8% [placebo] for GLACIAL). In patients receiving 300 mg of omalizumab with 24 weeks of treatment, median time to achieve a UAS7 ≤ 6 was 6 weeks (ASTERIA I and GLACIAL) and median time to achieve a UAS7 = 0 was 12 or 13 weeks (ASTERIA I and GLACIAL, respectively). Some patients who achieved well-controlled urticaria or complete response sustained response throughout the treatment period. Conclusion: Benefits of omalizumab treatment were evident early (before week 4) in some patients and persisted to week 24. Use of 300 mg of omalizumab demonstrated best results in controlling CIU/CSU symptoms.
- Omalizumab efficacy in cases of chronic spontaneous urticaria is not explained by the inhibition of sera activity in effector cells(Nature Publishing Group, 2017) Serrano-Candelas, E. (Eva); Gastaminza, G. (Gabriel); Audicana, M.T. (María T.); Martínez-Aranguren, R. (Rubén); Bartra, J. (Joan); Martín, M. (Margarita); Algorta, J. (Jaime); Vega, O. (Olga); Ferrer-Cardona, M. (Marta); Nuñez-Cordoba, J.M. (Jorge M.); Valero-Santiago, A. (Antonio)Omalizumab (OmAb) is a humanized anti-IgE antibody approved for the treatment of chronic spontaneous urticaria (CSU). OmAb's mechanism of action is known to include actions on free IgE and on pre-bound IgE. However, OmAb is equally and rapidly effective against autoimmune and non-autoimmune urticaria where IgE involvement is not clear, suggesting the involvement of additional mechanisms of action. In this study, we sought to investigate the ability of OmAb to inhibit mast cell and basophil degranulation induced by sera from CSU patients. For this purpose, we performed a comparison between the in vitro incubation of sera from CSU patients treated with OmAb and the in vivo administration of OmAb in a clinical trial. We found that OmAb added in vitro to sera from CSU patients did not modify the ability of the sera to induce cell degranulation. Similarly, the sera from patients treated with OmAb in the context of the clinical trial who had a good clinical outcome maintained the capacity to activate mast cells and basophils. Thus, we conclude that the beneficial activity of OmAb does not correlate with the ability of patient sera to induce cell degranulation.
- Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA²LEN position paper(Wiley-Blackwell, 2022) Brockow, K. (Knut); Arasi, S. (Stefania); Ebisawa, M. (Motohiro); Galvin, A.D. (Audrey Dunn); Arshad, H. (Hasan); Cianferoni, A. (Antonella); Bousquet, J.J. (Jean J.); Bindslev-Jensen, C. (Carsten); Angier, E. (Elizabeth); Custovic, A. (Adnan); Bégin, P. (Philippe); Dörr, T. (Tamara); Jong, N. (Nicolette) de; Cork, M.J. ( Michael J.); Aberer, W. (Werner); Alvaro, M. (Montserrat); Bartra, J. (Joan); Deschildre, A. (Antoine); Beck, L. (Lisa); Deleanu, D. (Diana); Giacco, S. (Stefano) del; Zuberbier, T. (Torsten); Fernández-Rivas, M. (Montserrat); Bush, A. (Andrew); Bislimovska, J. (Jovanka); Darsow, U. (Ulf); Ballmer-Weber, B. (Barbara); Ferrer-Cardona, M. (Marta)Background: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. Conclusion: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.
- Biomarkers predicting the controller dose of omalizumab in patients with chronic spontaneous urticaria(Blackwell Scientific Publications, 2024) Testera-Montes, A. (A.); Torres-Jaén, M.J. (María Josefa); Eguiluz-Gracia, I. (I.); Vega-Chicote, J.M. (J. M.); Zubiaga-Fernandez, L. (L.); Bartra, J. (Joan); Gómez-Pérez, F. (Francisca); Rondon, C. (C.); Perez-Sanchez, N. (N.); Ferrer-Cardona, M. (Marta)Background: Clinical trials showed the efficacy of 300 mg/4 weeks of omalizumab (OMA) during 6 months in patients with severe chronic spontaneous urticaria (CSU). Nevertheless, in real life, many patients require higher doses and/or longer treatment. This study assesses the real-life performance of OMA in severe CSU and identifies factors associated with the response. Methods: CSU patients eligible for OMA were recruited prospectively. Clinical data and a blood test were collected before OMA initiation. Urticaria Activity Score 7 (UAS7) was calculated at baseline and every 3 months during OMA treatment. CSU control was defined as UAS7 <7 points. This work was partially sponsored by OMA manufacturer. Results: Eighty-nine adults (19.1% males) with severe CSU were recruited. Median duration of CSU prior to OMA initiation was 2 years, and median severity by UAS7 at baseline was 24 points (range 10-42 points). OMA controlled 94.4% of patients, but 17.9% of responders required doses >300 mg/4 weeks. A blood basophil count >20 cells/μL (OR 13.33; 95% CI 3.32-52.63; p < .001) and the absence of hypothyroidism (OR 3.65; 95% CI 0.78-16.95; p = .099) were identified as predictive factors to achieve control with 300 mg/4 weeks. Twelve patients were able to stop OMA during the study (responders in remission, RR). RR had received OMA for a median of 29 months (12-53 months). Conversely, 32 patients had been on OMA for >29 months at the end of the study (active responders, AR). AR had received OMA for a median of 45 months (30-100 months). There were no significant differences in clinical or analytical factors between RR and AR patients. Conclusions: Low blood basophil count and the presence of hypothyroidism might serve as biomarkers for the controller dose of OMA in severe CSU patients.
- Unveiling chronic spontaneous urticaria pathophysiology through systems biology(Elsevier, 2023) Artigas, L. (Laura); Gómez. J. (Jessica); Smeets, S. (Serge); Savic, S. (Sinisa); Segu-Verges, C. (Cristina); Terradas-Montana, P. (Pau); Ferrer-Cardona, M. (Marta)Background: Chronic spontaneous urticaria (CSU) is a rare, heterogeneous, severely debilitating, and often poorly controlled skin disease resulting in an itchy eruption that can be persistent. Antihistamines and omalizumab, an anti-IgE mAb, are the only licensed therapies. Although CSU pathogenesis is not yet fully understood, mast cell activation through the IgE:high-affinity IgE receptor (FcεRI) axis appears central to the disease process. Objective: We sought to model CSU pathophysiology and identify in silico the mechanism of action of different CSU therapeutic strategies currently in use or under development. Methods: Therapeutic performance mapping system technology, based on systems biology and machine learning, was used to create a CSU interactome validated with gene expression data from patients with CSU and a CSU model that was used to evaluate CSU pathophysiology and the mechanism of action of different therapeutic strategies. Results: Our models reflect the known role of mast cell activation as a central process of CSU pathophysiology, as well as recognized roles for different therapeutic strategies in this and other innate and adaptive immune processes. They also allow determining similarities and differences between them; anti-IgE and Bruton tyrosine kinase inhibitors play a more direct role in mast cell biology through abrogation of FcεRI signaling activity, whereas anti-interleukins and anti-Siglec-8 have a role in adaptive immunity modulation. Conclusion: In silico CSU models reproduced known CSU and therapeutic strategies features. Our results could help advance understanding of therapeutic mechanisms of action and further advance treatment research by patient profile.
- Autoimmune diseases are linked to type IIb autoimmune chronic spontaneous urticaria(Korean Academy of Asthma, Allergy and Clinical Immunology, Korean Academy of Pediatric Allergy and Respiratory Disease, 2021) Altrichter, S. (Sabine); Sussman, G. (Gordon); Kinaciyan, T. (Tamar); Makris, M. (Michael); Zhang, K. (Ke); Asero, R. (Riccardo); Daschner, A. (Alvaro); Kolkhir, P. (Pavel); Metz, M. (Martin); Kromminga, A. (Arno); Skov, P.S. (Per Stahl); Jakob, T. (Thilo); Konstantinou, G.N. (George N.); Maurer, M. (Marcus); Hawro, T. (Tomasz); Gimenez-Arnau, A. (Ana); Staubach, P. (Petra); Ferrer-Cardona, M. (Marta)Purpose: Patients with chronic spontaneous urticaria (CSU) have an increased risk for comorbid autoimmune diseases. In this retrospective multicenter study of CSU patients, we evaluated clinical and laboratory features of CSU associated with a higher risk of comorbid autoimmune diseases. Methods: We analyzed records of CSU patients (n = 1,199) for a history or presence of autoimmune diseases. Patients were diagnosed with type IIb autoimmune CSU (aiCSU) if all 3 tests were positive: autologous serum skin test (ASST), basophil histamine release assay (BHRA) and/or basophil activation test (BAT), and IgG autoantibodies against FcεRIα/IgE detected by immunoassay. Results: Twenty-eight percent of CSU patients had at least 1 autoimmune disease. The most prevalent autoimmune diseases were Hashimoto's thyroiditis (HT) (≥ 21%) and vitiligo (2%). Two percent of CSU patients had ≥ 2 autoimmune diseases, most frequently HT plus vitiligo. Comorbid autoimmune diseases, in patients with CSU, were associated with female sex, a family history of autoimmune diseases, and higher rates of hypothyroidism and hyperthyroidism (P < 0.001). Presence of autoimmune diseases was linked to aiCSU (P = 0.02). The risks of having autoimmune diseases were 1.7, 2.9 and 3.3 times higher for CSU patients with a positive ASST, BHRA and BAT, respectively. In CSU patients, markers for autoimmune diseases, antinuclear antibodies and/or IgG anti-thyroid antibodies were associated with non-response to omalizumab treatment (P = 0.013). Conclusions: In CSU, autoimmune diseases are common and linked to type IIb autoimmune CSU. Our results suggest that physicians assess and monitor all adult patients with CSU for signs and symptoms of common autoimmune diseases, especially HT and vitiligo.
- Improvement of drug prescribing in acute kidney injury with a nephrotoxic drug alert system(BMJ, 2019) Idoate, A. (Antonio); Garcia-Fernandez, N. (Nuria); Aquerreta, I. (Irene); Arias-Pou, P. (Paloma)Electronic alert systems have shown their capacity for improving the detection of acute kidney injury (AKI). The aim of this study was to design and implement a clinical decision support system (CDSS) for improving drug selection and reducing nephrotoxic drug use in patients with AKI.