Efectividad de guselkumab en pacientes con hidradenitis supurativa en condiciones de práctica clínica: estudio retrospectivo y multicéntrico en España

Biologics; Hidradenitis suppurativa; GuselkumabProductos biológicos; Hidradenitis supurativa; GuselkumabBiològics; Hidradenitis supurativa; GuselkumabBackground: Hidradenitis suppurativa (HS) is a chronic skin condition causing lesions in which high levels of interleukin (IL)-23 and T-helper 17 cells are found. Adalimumab remains the only approved treatment. Guselkumab, an antibody targeting the p19 protein subunit of extracellular IL-23, is approved for the treatment of moderate-severe psoriasis, but evidence on its efficacy in treating HS is limited. Objectives: To assess the effectiveness and safety of guselkumab in treating moderate-severe HS under clinical practice conditions. Methods: A multicentre retrospective observational study was carried out in 13 Spanish Hospitals including adult HS patients treated with guselkumab within a compassionate use programme (March 2020-March 2022). Data referred to patient demographic and clinical characteristics at treatment initiation (baseline), patient-reported outcomes (Numerical Pain Rating Scale [NPRS] and Dermatology Life Quality Index [DLQI]), physician scores (International Hidradenitis Suppurativa Severity Score System [IHS4], HS Physical Global Score [HS-PGA] and Hidradenitis Suppurativa Clinical Response [HiSCR]) were recorded at baseline and at 16, 24, and 48 weeks of treatment. Results: A total of 69 patients were included. Most (84.10%) had severe HS (Hurley III) and had been diagnosed for over ten years (58.80%). The patients had been subjected to multiple non-biological (mean 3.56) or biological (mean 1.78) therapies, and almost 90% of those treated with biologics had received adalimumab. A significant decrease in IHS4, HS-PGA, NPRS, and DLQI scores was observed from baseline to 48 weeks of guselkumab treatment (all p<0.01). HiSCR was achieved in 58.33% and 56.52% of the patients at 16 and 24 weeks, respectively. Overall, 16 patients discontinued treatment, mostly due to inefficacy (n=7) or loss of efficacy (n=3). No serious adverse events were observed. Conclusions: Our results indicate that guselkumab may be a safe and effective therapeutic alternative for patients with severe HS that fail to respond to other biologics

The older, the wiser? profiles of string instrument teachers with different experience according to their conceptions of teaching, learning, and evaluation

When posting or re-using the article, you should provide a link/URL from the article posted to the SAGE Journals Online site where the article is published: http://online.sagepub.com and please make the following acknowledgment: ‘The final, definitive version of this paper has been published in , Vol/Issue, Month/Year by SAGE Publications Ltd, All rights reserved. © [The Author(s)]Recent research on music teaching and the curricula proposed in different countries increasingly insists on moving towards teaching centered on managing students' mental processes according to the constructivist approach. However, studies on conceptions and practices of teaching-learning show that these still largely focus on transmitting the musical and technical knowledge needed to produce the correct sound. Our main aim was to study the conceptions of teaching-learning held by 53 string teachers at elementary levels, and to test how they are affected by the variable teaching experience (in three groups: [a] less than 7 years; [b] 7-14 years; and [c] more than 14 years). We also wanted to determine whether these conceptions give rise to consistent profiles in three pedagogical dimensions: teaching, learning, and evaluation. We collected data by means of a multiple-choice questionnaire, and applied cluster analysis, correlations, analysis of variance (ANOVA), and post hoc tests. Agreeing with prior research, we found three distinct profiles in the answers to the questionnaire: direct, interpretative, and constructive. Teachers' beliefs were more constructive regarding teaching and evaluation than regarding learning, although younger teachers held more complex positions regarding teaching and learning music, in contrast to much research on teaching-expertise

The Inflammatory Response After Ischemic Stroke: Targeting β\u3csub\u3e2\u3c/sub\u3e and β\u3csub\u3e1\u3c/sub\u3e Integrins

Ischemic stroke is a leading cause of death and disability with limited therapeutic options. Resulting inflammatory mechanisms after reperfusion (removal of the thrombus) result in cytokine activation, calcium influx, and leukocytic infiltration to the area of ischemia. In particular, leukocytes migrate toward areas of inflammation by use of integrins, particularly integrins β1 and β2. Integrins have been shown to be necessary for leukocyte adhesion and migration, and thus are of immediate interest in many inflammatory diseases, including ischemic stroke. In this review, we identify the main integrins involved in leukocytic migration following stroke (αLβ2, αDβ2, α4β1, and α5β1) and targeted clinical therapeutic interventions

The Road Less Traveled: Regulation of Leukocyte Migration Across Vascular and Lymphatic Endothelium by Galectins

Leukocyte entry from the blood into inflamed tissues, exit into the lymphatics, and migration to regional lymph nodes are all crucial processes for mounting an effective adaptive immune response. Leukocytes must cross two endothelial cell layers, the vascular and the lymphatic endothelial cell layers, during the journey from the blood to the lymph node. The proteins and cellular interactions which regulate leukocyte migration across the vascular endothelium are well studied; however, little is known about the factors that regulate leukocyte migration across the lymphatic endothelium. Here, we will summarize evidence for a role for galectins, a family of carbohydrate-binding proteins, in regulating leukocyte migration across the vascular endothelium and propose that galectins are also involved in leukocyte migration across the lymphatic endothelium

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Reproducibility of Transcranial Doppler ultrasound in the middle cerebral artery

Abstract Background Transcranial Doppler ultrasound remains the only imaging modality that is capable of real-time measurements of blood flow velocity and microembolic signals in the cerebral circulation. We here assessed the repeatability and reproducibility of transcranial Doppler ultrasound in healthy volunteers and patients with symptomatic carotid artery stenosis. Methods Between March and August 2017, we recruited 20 healthy volunteers and 20 patients with symptomatic carotid artery stenosis. In a quiet temperature-controlled room, two 1-h transcranial Doppler measurements of blood flow velocities and microembolic signals were performed sequentially on the same day (within-day repeatability) and a third 7–14 days later (between-day reproducibility). Levels of agreement were assessed by interclass correlation co-efficient. Results In healthy volunteers (31±9 years, 11 male), within-day repeatability of Doppler measurements were 0.880 (95% CI 0.726–0.950) for peak velocity, 0.867 (95% CI 0.700–0.945) for mean velocity, and 0.887 (95% CI 0.741–0.953) for end-diastolic velocity. Between-day reproducibility was similar but lower: 0.777 (95% CI 0.526–0.905), 0.795 (95% CI 0.558–0.913), and 0.674 (95% CI 0.349–0.856) respectively. In patients (72±11 years, 11 male), within-day repeatability of Doppler measurements were higher: 0.926 (95% CI 0.826–0.970) for peak velocity, 0.922 (95% CI 0.817–0.968) for mean velocity, and 0.868 (95% CI 0.701–0.945) for end-diastolic velocity. Similarly, between-day reproducibility revealed lower values: 0.800 (95% CI 0.567–0.915), 0.786 (95% CI 0.542–0.909), and 0.778 (95% CI 0.527–0.905) respectively. In both cohorts, the intra-observer Bland Altman analysis demonstrated acceptable mean measurement differences and limits of agreement between series of middle cerebral artery velocity measurements with very few outliers. In patients, the carotid stenoses were 30–40% (n = 9), 40–50% (n = 6), 50–70% (n = 3) and > 70% (n = 2). No spontaneous embolisation was detected in either of the groups. Conclusions Transcranial Doppler generates reproducible data regarding the middle cerebral artery velocities. However, larger studies are needed to validate its clinical applicability. Trial registration ClinicalTrial.gov (ID NCT 03050567), retrospectively registered on 15/05/2017

Estudio del sistema nervioso central en pacientes con anemia drepanocítica Study of the central nervous system in patients with drepanocytic anemia

Se estudiaron 35 pacientes adultos con anemia drepanocítica. Se establecieron 2 grupos: grupo 1: 24 enfermos sin antecedentes de crisis del sistema nervioso central (15 hombres; 9 mujeres) y grupo 2: 11 casos con antecedentes de crisis (6 hombres; 5 mujeres). El promedio de edad fue de 31 años en el sexo masculino y de 29 años en el femenino. Todos los enfermos estaban en condiciones basales. El tiempo transcurrido entre la crisis y el estudio fue de 4,7 años. No hubo diferencia significativa en las cifras de hemoglobina y los reticulocitos entre ambos grupos. Se encontró aumento significativo de la velocidad sanguínea cerebral en todos los pacientes del grupo 1 y del grupo 2 (p < 0,05 y p < 0,001, respectivamente). En 13 pacientes del grupo 1 (54,1 %) el flujo sanguíneo cerebral presentó modificación, mientras que en todos los pacientes del grupo 2 se encontró alterado. En 13 casos del grupo 1 (76,4 %) el electroencefalograma fue normal y en el 87,5 % de los enfermos del grupo 2 estaba alterado. En 4 pacientes del grupo 1 (23,5 %) la actividad eléctrica cerebral presentó alguna modificación. En 19 individuos del grupo 1 (95 %) la tomografía axial computarizada fue normal y en 3 casos del grupo 2 (37,5 %) se observó alguna alteración.<br>35 adult patients with drepanocytic anemia were studied. They were divided into 2 groups: group 1 was composed of 24 patients without history of central nervous system crisis (15 males and 9 females), whereas group 2 included 11 cases with crisis history (6 males and 5 females). Average age was 31 years old for males and 29 for females. All the patients were under basal conditions. The time elapsed between the crisis and the study was 4.7 years. No significant differences were observed between the hemoglobin figures and the reticulocytes of both groups. A marked increase of the brain blood velocity was found in all the patients from group 1 and group 2 (p < 0.05 y p < 0.001, respectively). In 13 patients from group 1 (54.1 %) the brain blood flow presented modifications, whereas it was altered in all patients from group 2. In 13 cases from group 1 (76.4 %) the electroencephalogram was normal, but it was altered in 87.5 % of the patients from group 2. In 4 patients from group 1 (23.5 %), the brain electrical activity showed some modification. Computerized axial tomography was normal in 19 patients from group 1. Some alteration was detected in 3 cases from group 2 (37.5 %)