Effectiveness and safety of guselkumab for the treatment of psoriasis in real-world settings at 24 weeks : A retrospective, observational, multicentre study by the Spanish Psoriasis Group

Altres ajuts: Acord transformatiu CRUE-CSICData on the effectiveness and safety of a drug in real-world clinical practice complement the evidence from clinical trials, which are carried out in a different setting. Little has been published on the effectiveness and safety of guselkumab in the treatment of psoriasis in clinical practice. The ojective of this study was to assess the effectiveness and safety of guselkumab at 24 weeks in patients with moderate to severe plaque psoriasis in routine clinical practice. A retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis treated with guselkumab for at least 24 weeks was carried out in Spain. We studied 343 patients, 249 of whom were followed for 24 weeks. By week 24, the mean (SD) psoriasis area severity index (PASI) had decreased from 11.1 (7.3) to 1.7 (2.8) (−9.3; [−10.2;-8.4]), 85.9% of the patients had achieved PASI score of 4 or less and 77.9% a PASI score of 2 or less. In terms of relative PASI response, 59.4% of the patients achieved a PASI-90 response and 49.0% a PASI-100 response. On multivariate analysis, two factors reduced the probability of a PASI of 2 or less at 24 weeks: a BMI ≥30 (OR, 0.44; 95% CI, 0.22-0.88) and a greater previous exposure to biologic therapy (OR, 0.69; 95% CI, [0.56-0.84]). Adverse events were rare (9.9%) and led to withdrawal from treatment in only nine patients (2.6%) by the end of the follow-up period. The results of this study confirm the high efficacy and safety of guselkumab indicated by the clinical trial data. In clinical practice, the absolute PASI score appears to be a better marker of response to treatment than the relative value

VETTONIA PROJECT: A VIRTUAL ENVIRONMENT FOR THE EDUCATIONAL DISSEMINATION OF THE IRON AGE

The VETTONIA project aims to disseminate the rich heritage from the Iron Age of the western Iberian Peninsula and the archaeological investigations carried out on this topic in recent years. The project utilizes new technologies such as virtual tours, 3D models, and impressions to create interactive and stimulating ways to access the results of the most recent archaeological research. Using these resources, lectures and seminars are being given in various forums with diverse types of audiences to present the virtual tours and the rest of the dissemination initiatives. In addition, the project presents its different initiatives during the annual archaeological interventions developed in the oppidum of Ulaca (Solosancho, Ávila, Spain), with good reception by the attending public. The VETTONIA project represents a pioneering dissemination experience that takes advantage of the educational opportunities offered by new technologies. In the future, tools such as virtual tours to archaeological sites may prove essential in classroom teaching at different levels and could promote sustainable tourism in fragile natural environments such as those that constitute the major settlements of the Late Iron Age (ca. 400–50 BC)

Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Gastrojejunal anastomosis stricture after laparoscopic gastric bypass: Our experience with 62 patients Estenosis de la anastomosis gastroyeyunal en el bypass gástrico laparoscópico: Nuestra experiencia con 62 pacientes

Objective: gastrojejunal stricture (GYS), not only is a common complication after laparoscopic gastric bypass (LGBP), but its frequency is about 15% according to bibliography. Our aim is to present our experience after 62 LGBP. Patients and method: from January 2004 to September-2006, we performed 62 consecutive laparoscopic gastric bypass (Wittgrove's technique). The gastrojejunal anastomosis is performed with auto suture material type CEAA No 21 termino-lateral (ILS, Ethicon). In 4 cases (6.45%) was converted to laparotomy, perform the anastomosis in the same way. Monitoring has a range of 3-35 months, conducted in 61 patients because one patient died of pulmonary thromboembolism in the immediate postoperative period after reoperation, after two weeks of gastric bypass, by necrosis of a small fragment of the remnant gastric. In all patients with persistent feeding intolerance were performed barium transit and/or gastroscopy. When gastrojejunal stricture showed proceeded to endoscopic pneumatic dilation (recommending dilate the anastomosis to a maximum 1.5 cm). Results: five cases (8.1%) developed a gastrojejunal stricture, in 4 of these cases the initial diagnosis was made by barium transit and in 1 case by endoscopy. Two patients had a history of digestive bleeding that required endoscopic sclerosis of the bleeding lesion (circumferentially sclerosis within 48 hours of surgery and sclerosis of bleeding points). All cases were resolved by endoscopic dilatation. At follow-up has not been detected re-stricture. Conclusion: Clinically, gastrojejunal stricture results in a progressive oral intolerance, revealing stenosis between 1 and 3 months postoperatively. The situations of sclerosis of the bleeding lesions favor, especially in cases of extensive sclerosis. In cases of suspected barium transit offers us a high diagnostic yield. Endoscopic dilatation resolved, so far, all cases.<br>Objetivo: la estenosis de la anastomosis gastroyeyunal representa una complicación nada desdeñable en la cirugía bariátrica por laparoscopia, llegándose, en algunas series, a alcanzar el 15%. Presentamos nuestra casuística en una serie de 62 casos consecutivos y el manejo realizado. Pacientes y método: desde enero-2004 a septiembre-2006 hemos realizado de manera consecutiva 62 bypass gástricos por laparoscopia según técnica de Wittgrove modificada. La anastomosis gastroyeyunal se realiza con material de autosutura tipo CEAA nº 21 término-lateral (ILS; Ethicon) y después de comprobar la estanqueidad anastomótica se dan dos puntos de válvula tipo Hoffmeister a cada lado de la anastomosis. En 4 casos (6,45%) se reconvirtió a laparotomía, realizándose la anastomosis de la misma manera. El seguimiento tiene un rango de 3-35 meses, realizado en 61 enfermos, pues un paciente falleció por tromboembolismo pulmonar en el postoperatorio inmediato tras reintervención, a las dos semanas del bypass gástrico, por necrosis de un pequeño fragmento del remanente gástrico. En todos los pacientes con intolerancia persistente a la alimentación se realizó tránsito baritado y/o gastroscopia. Cuando se evidenció estenosis gastroyeyunal se procedió a dilatación neumática endoscópica (recomendando dilatar la anastomosis hasta como máximo 1,5 cm). Resultados: en 5 casos (8,1%) se desarrolló una estenosis gastroyeyunal, en 4 de estos casos el diagnóstico inicial fue por tránsito baritado y en 1 caso por endoscopia. Dos pacientes tenían antecedentes de HDA que precisaron esclerosis endoscópica de la lesión sangrante (esclerosis circunferencial a las 48 horas de la cirugía y esclerosis de puntos sangrantes). Todos los casos se resolvieron mediante dilatación endoscópica, precisando en dos casos dos sesiones de dilatación y el resto una. En el seguimiento no se han detectado re-estenosis. Conclusión: la estenosis gastroyeyunal es consecuencia de realizar una anastomosis de pequeño calibre (con vistas a evitar así el rápido vaciamiento del bolsón gástrico), hecho también favorecido por la anastomosis circular. Clínicamente se traduce en una intolerancia oral progresiva, evidenciándose la estenosis entre el 1er y 3 er mes postoperatorios. Las situaciones de esclerosis de lesiones sangrantes la favorecen, sobre todo en aquellos casos de esclerosis amplias. En aquellos casos de sospecha el tránsito baritado nos ofrece un alto rendimiento diagnóstico. La dilatación endoscópica ha resuelto, hasta la fecha, todos los casos

Moderate to Severe Psoriasis in Pediatric and Young Patients: The BIOBADADERM Registry Experience

Childhood-onset psoriasis generally follows an indolent course but patients with moderate or severe disease may require systemic treatment. The aim of this study was to determine the relative proportion of children and young people aged up to 21 years with moderate to severe psoriasis in the BIOBADADERM registry and to analyze the characteristics of these patients, treatments used, and adverse events. Of the 3946 patients in the registry, 24 were aged 21 years or younger. The mean age of this group when they started treatment upon registration on Biobadaderm was 16.1 years and the mean Psoriasis Area and Severity Index was 9.4. In 67% the first treatment recorded was with a conventional systemic drug. Treatment was discontinued in 14 patients (58%) due to adverse events or a loss or lack of effectiveness. In conclusion, the BIOBADADERM registry shows that young people account for a small proportion of psoriasis patients receiving systemic treatment, and they are more likely to be treated using conventional systemic drugs. (C) 2021 AEDV. Published by Elsevier Espana, S.L.U