Classification and treatment of angioedema without wheals: A spanish delphi consensus

Introduction Problems in the defnition and classifcation of angioedema, leading to difculties in its diagnosis and treatment, have been identifed; therefore, an improvement in the current classifcation of angioedema is required. Objective The aim of this study was to propose a practical classifcation of angioedema without wheals that helps to establish a diferential diagnosis and take appropriate therapeutic decisions. Methods An initial proposal of classifcation of angioedema without wheals was agreed by a scientifc committee of experts and was subsequently validated by a panel of experts by means of consensus based on the Delphi methodology. Forty-fve items on the classifcation, diagnosis, and treatment of angioedema without wheals were proposed for the survey. Results Most items (93.8%) were agreed after two rounds. All panelists agreed with the proposed classifcation, as well as with most of the clinical and treatment characteristics. The angioedema without wheals classifcation established three groups: histamine-mediated, bradykinin-mediated, and unknown mechanism angioedema. The clinical characteristics of the proposed types of angioedema were also agreed, except for the allergic histamine-mediated and unknown mechanism angioedema, which generated debate. Regarding treatments, although there was broad agreement with the proposed items, a lack of knowledge about some treatments in this pathology was observed. Conclusion The proposed classifcation of angioedema without wheals was accepted with a high degree of agreement; however, knowledge of available treatments needs to be increased and the defnition of angioedema of unknown mechanism needs to be improved

Favoring alkane primary carbon-hydrogen bond functionalization in supercritical carbon dioxide as reaction medium

The selectivity of a catalytic alkane functionalization process can be modified just changing the reaction medium from neat alkane to supercritical carbon dioxide (scCO2). A silica supported copper complex bearing an Nheterocyclic carbene ligand promotes the functionalization of carbon-hydrogen bonds of alkanes by transferring the CHCO2Et group from N2=CHCO2Et (ethyl diazoacetate, EDA). In neat hexane only 3% of the primary C-H bonds (ethyl heptanoate being the product) are functionalized in that manner, whereas the same reaction carried out in scCO2 provides a 30% yield in this linear ester. Such effect seems to be induced by an electronic density flux from the NHC ligand to the surrounding carbon dioxide molecules.We thank MINECO (CTQ2017-82893-C2-1-R, CTQ2014- 52769-C3-R-2 and CTQ2014-57761-R) and Junta de Andalucía for Grant P12-FQM-1765. J.T.S. thanks MINECO for a FPI fellowship. We acknowledge the SCSIE (Universidad de Valencia) for access to instrumental facilities. We thank Prof. Jesús de la Rosa (Centro de Investigación en Química Sostenible, Universidad de Huelva, Spain) for ICP-MS data

Hereditary angioedema: quality of life in Brazilian patients

OBJECTIVE: Hereditary angioedema is a serious medical condition caused by a rare autosomal dominant genetic disorder and it is associated with deficient production or dysfunction of the C1 esterase inhibitor. In most cases, affected patients experience unexpected and recurrent crises of subcutaneous, gastrointestinal and laryngeal edema. The unpredictability, intensity and other factors associated with the disease impact the quality of life of hereditary angioedema patients. We evaluated the quality of life in Brazilian hereditary angioedema patients. METHODS: Patients older than 15 years with any severity of hereditary angioedema and laboratory confirmation of C1 inhibitor deficiency were included. Two questionnaires were used: a clinical questionnaire and the SF-36 (a generic questionnaire). This protocol was approved by the Ethics Committee of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. RESULTS: The SF-36 showed that 90.4% (mean) of all the patients had a score below 70 and 9.6% had scores equal to or higher than 70. The scores of the eight dimensions ranged from 51.03 to 75.95; vitality and social aspects were more affected than other arenas. The internal consistency of the evaluation was demonstrated by a Cronbach's alpha value above 0.7 in seven of the eight domains. CONCLUSIONS: In this study, Brazilian patients demonstrated an impaired quality of life, as measured by the SF-36. The most affected domains were those related to vitality and social characteristics. The generic SF-36 questionnaire was relevant to the evaluation of quality of life; however, there is a need for more specific instruments for better evaluation

Concepciones culturales del VIH/Sida de adolescentes de Bolivia, Chile y México

OBJETIVO: Comprender las dimensiones culturales del VIH/Sida de estudiantes adolescentes. MÉTODOS: Estudio antropológico cognitivo. Realizado en Cochabamba (Bolivia), Talca (Chile) y Guadalajara (México) entre 2007 y 2008. Un total de 184 jóvenes (de 14 y 19 años de edad) fueron seleccionados por muestreo propositivo en centros de estudios de educación media superior de cada país. Fueron utilizadas las técnicas de listados libres y el sorteo de montones. Se indagaron términos asociados al concepto VIH/Sida y grupos de dimensiones conceptuales. Posteriormente se aplicó análisis de consenso mediante factorización de componentes principales y análisis dimensional mediante conglomerados jerárquicos y escalas multidimensionales. RESULTADOS: Las diferencias entre los contextos fueron en el grado de consenso en relación al término de VIH/Sida, ya que fue mayor en Cochabamba. En Talca y Guadalajara los jóvenes mencionaron metáforas de lucha frente a la enfermedad, mientras en Cochabamba se refirieron a la ayuda, apoyo y amor que las personas infectadas deberían recibir. Las coincidencias entre las conceptualizaciones de los jóvenes de los tres países fueron: los riesgos (las prácticas sexuales desprotegidas y el contacto con algunos grupos poblacionales específicos), las consecuencias (muerte física y social, entendida ésta última como el rechazo de la sociedad hacia los enfermos) y la prevención de la enfermedad (con base en la información así como uso del condón). CONCLUSIONES: Para los estudiantes adolescentes el VIH/Sida es una enfermedad causada por prácticas sexuales y consumo de drogas que implica daño, dolor y muerte. Los programas preventivos del VIH/Sida para los adolescentes deben promover la búsqueda de información sobre el tema con bases científicas, y no centrarse en las consecuencias emocionales y sociales de la enfermedad.OBJETIVO: Compreender as dimensões culturais do HIV/Aids por estudantes adolescentes. MÉTODOS: Estudo antropológico cognitivo realizado em Cochabamba (Bolívia), Talca (Chile) e Guadalajara (México), entre 2007 e 2008. O total de 184 jovens (de 14 e 19 anos de idade) foi selecionado por amostragem propositiva em centros de estudos de educação média superior de cada país. Foram utilizadas técnicas de listas livres e classificação da pilha. Foi feita a indagação de termos associados ao conceito HIV/Aids e grupos de dimensões conceituais. Posteriormente, fez-se análise de consenso mediante a fatorização dos componentes principais e análise dimensional mediante conglomerados hierárquicos e escalas multidimensionais. RESULTADOS: As diferenças entre os contextos foram no grau de consenso em relação ao termo HIV/Aids, que foi maior em Cochabamba. Em Talca e Guadalajara os jovens mencionaram metáforas de luta diante da doença, enquanto em Cochabamba eles referiram ajuda, apoio e amor que as pessoas infectadas deveriam receber. As coincidências entre as conceitualizações dos jovens dos três países foram: os riscos (as práticas sexuais desprotegidas e o contato com alguns grupos populacionais específicos), as conseqüências (morte física e social, entendida esta última como o rechaço da sociedade aos doentes) e a prevenção da doença (com base na informação e no uso do preservativo). CONCLUSIONES: Para os estudantes adolescentes, o HIV/Aids é uma doença causada por práticas sexuais e uso de drogas que envolve dano, dor e morte. Os programas preventivos do HIV/Aids para os e as adolescentes devem promover a busca de informação com bases científicas sobre o tema, e não só a que se centra nas conseqüências emocionais e sociais da doença.OBJECTIVE: To understand the cultural dimensions of HIV/AIDS among adolescent students. METHODS: A cognitive anthropological study was undertaken in Cochabamba (Bolivia), Talca (Chile) and Guadalajara (Mexico), during 2007 and 2008. A total of 184 teenagers (from 14 to 19 years old) were selected by purposeful sampling at secondary schools in each country. Free association lists and pile sorts were utilized. Terms associated with the concept of HIV/AIDS and groups of conceptual dimensions were investigated. Subsequently, consensus analysis was performed using factorial principal components and dimensional analysis through hierarchical clusters and multidimensional scales. RESULTS: The differences between the country contexts were in the degree of consensus in relation to the term HIV/AIDS, which was greater in Cochabamba. In Talca and Guadalajara the youths mentioned metaphors of fighting against HIV/AIDS, while in Cochabamba participants talked about help, support and love that infected people should receive. The similarities among conceptions by youth from the three countries were: the risk factors (unprotected sexual practice and contact with specific population groups), the consequences (physical and social death, being the latter understood as social rejection of people living with HIV/AIDS) and the prevention of illness (based on information and condom use). CONCLUSIONS: For adolescent students, HIV/AIDS is a disease caused by sexual practices and drug use and involves harm, pain and death. HIV/AIDS prevention programs for adolescents should promote science based information on the topic and not concentrate only on the emotional and social consequences of HIV/AIDS

Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals

Background and aims: Hepatic ischemia-reperfusion injury (IRI) is the leading cause of early posttransplantation organ failure as mitochondrial respiration and ATP production are affected. A shortage of donors has extended liver donor criteria, including aged or steatotic livers, which are more susceptible to IRI. Given the lack of an effective treatment and the extensive transplantation waitlist, we aimed at characterizing the effects of an accelerated mitochondrial activity by silencing methylation-controlled J protein (MCJ) in three preclinical models of IRI and liver regeneration, focusing on metabolically compromised animal models. Approach and results: Wild-type (WT), MCJ knockout (KO), and Mcj silenced WT mice were subjected to 70% partial hepatectomy (Phx), prolonged IRI, and 70% Phx with IRI. Old and young mice with metabolic syndrome were also subjected to these procedures. Expression of MCJ, an endogenous negative regulator of mitochondrial respiration, increases in preclinical models of Phx with or without vascular occlusion and in donor livers. Mice lacking MCJ initiate liver regeneration 12 h faster than WT and show reduced ischemic injury and increased survival. MCJ knockdown enables a mitochondrial adaptation that restores the bioenergetic supply for enhanced regeneration and prevents cell death after IRI. Mechanistically, increased ATP secretion facilitates the early activation of Kupffer cells and production of TNF, IL-6, and heparin-binding EGF, accelerating the priming phase and the progression through G1 /S transition during liver regeneration. Therapeutic silencing of MCJ in 15-month-old mice and in mice fed a high-fat/high-fructose diet for 12 weeks improves mitochondrial respiration, reduces steatosis, and overcomes regenerative limitations. Conclusions: Boosting mitochondrial activity by silencing MCJ could pave the way for a protective approach after major liver resection or IRI, especially in metabolically compromised, IRI-susceptible organs.Funding information: Supported by grants from Ministerio de Ciencia, Innovación y Universidades MICINN (PID2020-117116RB-100, RTI2018-096759-A-100, RTI2018-095114-B-I00, PID2019-108977RB-100 and RTI2018-095700-B100, integrado en el Plan Estatal de Investigación Científica y Técnica y Innovación, cofinanciado con Fondos FEDER, to M.L.M.-C., T.C.D., C.P., P.M.-S., and N.G.A.A., respectively), Subprograma Retos Colaboración RTC2019-007125-1; Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M.-C.); Asociación Española contra el Cáncer (to T.C.D. and M.S.-M); La Caixa Foundation Program (HR17-00601, to M.L.M.-C.), Proyectos Investigación en Salud DTS20/00138 (to M.L.M.-C.); Departamento de Industria del Gobierno Vasco (to M.L.M.-C.); Departamento de Educación del Gobierno Vasco (to N.G.-U. and J.S.); Acción Estratégica Ciber Emergentes 2018 (Ciberehd-ISCIII) and Gilead Sciences International Research Scholars Program in Liver Disease (to M.V.-R.); Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos IIIAcknowledgments: We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644). We acknowledge Begoña Rodríguez Iruretagoyena for the technical support provided

Factor analysis of the Zung self-rating depression scale in a large sample of patients with major depressive disorder in primary care

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the symptomatic dimensions of depression in a large sample of patients with major depressive disorder (MDD) in the primary care (PC) setting by means of a factor analysis of the Zung self-rating depression scale (ZSDS).</p> <p>Methods</p> <p>A factor analysis was performed, based on the polychoric correlations matrix, between ZSDS items using promax oblique rotation in 1049 PC patients with a diagnosis of MDD (DSM-IV).</p> <p>Results</p> <p>A clinical interpretable four-factor solution consisting of a <it>core depressive </it>factor (I); a <it>cognitive </it>factor (II); an <it>anxiety </it>factor (III) and a <it>somatic </it>factor (IV) was extracted. These factors accounted for 36.9% of the variance on the ZSDS. The 4-factor structure was validated and high coefficients of congruence were obtained (0.98, 0.95, 0.92 and 0.87 for factors I, II, III and IV, respectively). The model seemed to fit the data well with fit indexes within recommended ranges (GFI = 0.9330, AGFI = 0.9112 and RMR = 0.0843).</p> <p>Conclusion</p> <p>Our findings suggest that depressive symptoms in patients with MDD in the PC setting cluster into four dimensions: <it>core depressive, cognitive, anxiety </it>and <it>somatic</it>, by means of a factor analysis of the ZSDS. Further research is needed to identify possible diagnostic, therapeutic or prognostic implications of the different depressive symptomatic profiles.</p

Impact of measurable residual disease by decentralized flow cytometry: a PETHEMA real-world study in 1076 patients with acute myeloid leukemia

The role of decentralized assessment of measurable residual disease (MRD) for risk stratification in acute myeloid leukemia (AML) remains largely unknown, and so it does which methodological aspects are critical to empower the evaluation of MRD with prognostic significance, particularly if using multiparameter flow cytometry (MFC). We analyzed 1076 AML patients in first remission after induction chemotherapy, in whom MRD was evaluated by MFC in local laboratories of 60 Hospitals participating in the PETHEMA registry. We also conducted a survey on technical aspects of MRD testing to determine the impact of methodological heterogeneity in the prognostic value of MFC. Our results confirmed the recommended cutoff of 0.1% to discriminate patients with significantly different cumulative-incidence of relapse (-CIR- HR:0.71, P < 0.001) and overall survival (HR: 0.73, P = 0.001), but uncovered the limited prognostic value of MFC based MRD in multivariate and recursive partitioning models including other clinical, genetic and treatment related factors. Virtually all aspects related with methodological, interpretation, and reporting of MFC based MRD testing impacted in its ability to discriminate patients with different CIR. Thus, this study demonstrated that “real-world” assessment of MRD using MFC is prognostic in patients at first remission, and urges greater standardization for improved risk-stratification toward clinical decisions in AML.This study was supported by the Centro de Investigación Biomédica en Red – Área de Oncología - del Instituto de Salud Carlos III (CIBERONC; CB16/12/00369, CB16/12/00233, CB16/12/00284 and CB16/12/00400), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS No. PI16/01661, PI16/00517 and PI18/01946), Gerencia Regional de Salud de CyL (GRS 1346/A/16) and the Plan de Investigación de la Universidad de Navarra (PIUNA 2014-18). This study was supported internationally by the Cancer Research UK, FCAECC and AIRC under the Accelerator Award Program EDITOR

SF3B1, RUNX1 and TP53 Mutations Significantly Impact the Outcome of Patients With Lower-Risk Myelodysplastic Syndrome

[Introduction] Prognosis of patients with myelodysplastic syndrome (MDS), particularly the group with lower-risk disease (LR-MDS) is very heterogeneous. Several studies have described the prognostic value of recurrent somatic mutations in MDS including all risk categories. Recently, the incorporation of genomic data to clinical parameters defined the new Molecular International Prognostic Scoring System (IPSS-M).[Materials and Methods] In this study, we evaluated the impact of molecular profile in a series of 181 patients with LR-MDS and non-proliferative chronic myelomonocytic leukemia.[Results] Epigenetic regulators (TET2, ASXL1) and splicing (SF3B1) were the most recurrent mutated pathways. In univariate analysis, RUNX1 or TP53 mutations correlated with lower median overall survival (OS). In contrast, SF3B1 mutation was associated with prolonged median OS [95 months (95% IC, 32-157) vs. 33 months (95% CI, 19-46) in unmutated patients (P < 0.01)]. In a multivariate Cox regression model, RUNX1 mutations independently associated with shorter OS, while SF3B1 mutation retained its favorable impact on outcome (HR: 0.24, 95% CI, 0.1-0.5; P = 0.001). In addition, TP53 or RUNX1 mutations were identified as predictive covariates for the probability of leukemic progression (P < 0.001).[Conclusion] Incorporation of molecular testing in LR-MDS identified a subset of patients with expected poorer outcome, either due to lower survival or probability of leukemic progression.Peer reviewe