Efectos adversos cutáneos inmunomediados por los anti-TNF: revisión de 30 casos / Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases

Introducción Los fármacos biológicos inhibidores del factor de necrosis tumoral (TNF) alfa son usados para tratar diferentes enfermedades inflamatorias. A pesar de su adecuado perfil de seguridad, se han descrito reacciones paradójicas asociadas a estos tratamientos. Material y método Se ha realizado una revisión retrospectiva de los pacientes en tratamiento con un anti-TNF que hubiesen presentado una reacción paradójica con afectación cutánea visitados en el Servicio de Dermatología del Hospital Universitari Parc Taulí de Sabadell. Resultados Registramos 30 pacientes en tratamiento con un anti-TNF que desarrollaron un efecto adverso cutáneo inmunomediado en forma de psoriasis (90%), alopecia (6,7%) o dermatitis neutrofílica (3,3%). Adalimumab fue el fármaco más implicado (56,7%), seguido de infliximab (40%). La morfología de la reacción psoriasiforme más descrita es la generalizada en placas (62,9%), seguida de la pustulosis palmo-plantar (37%). El 43,3% de los pacientes mantuvieron el anti-TNF, y de ellos el 92,3% obtuvieron una resolución total y parcial. De los 5 pacientes que iniciaron otro anti-TNF, ninguno obtuvo una resolución total. De los 8 pacientes que cambiaron a un tratamiento biológico diferente al anti-TNF, el 62,5% obtuvieron una resolución total o parcial. Discusión La aparición de una reacción paradójica no siempre obliga al cambio de tratamiento biológico, puesto que se ha observado la resolución de las lesiones cutáneas con un tratamiento tópico y/o sistémico adicional en más de la mitad de los pacientes, sin necesidad de suspender el anti-TNF. Si la afectación es grave, se debe plantear el cambio de tratamiento biológico, siendo más eficaz iniciar un fármaco dirigido a una diana terapéutica distinta al anti-TNF (AU)

Background Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. Material and methods Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. Results We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. Conclusions Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases (AU)

[Translated article] Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases / Efectos adversos cutáneos inmunomediados por los anti-TNF: revisión de 30 casos

Background Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. Material and methods Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. Results We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. Conclusions Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases (AU)

Introducción Los fármacos biológicos inhibidores del factor de necrosis tumoral (TNF) alfa son usados para tratar diferentes enfermedades inflamatorias. A pesar de su adecuado perfil de seguridad, se han descrito reacciones paradójicas asociadas a estos tratamientos. Material y método Se ha realizado una revisión retrospectiva de los pacientes en tratamiento con un anti-TNF que hubiesen presentado una reacción paradójica con afectación cutánea visitados en el Servicio de Dermatología del Hospital Universitari Parc Taulí de Sabadell. Resultados Registramos 30 pacientes en tratamiento con un anti-TNF que desarrollaron un efecto adverso cutáneo inmunomediado en forma de psoriasis (90%), alopecia (6,7%) o dermatitis neutrofílica (3,3%). Adalimumab fue el fármaco más implicado (56,7%), seguido de infliximab (40%). La morfología de la reacción psoriasiforme más descrita es la generalizada en placas (62,9%), seguida de la pustulosis palmo-plantar (37%). El 43,3% de los pacientes mantuvieron el anti-TNF, y de ellos el 92,3% obtuvieron una resolución total y parcial. De los 5 pacientes que iniciaron otro anti-TNF, ninguno obtuvo una resolución total. De los 8 pacientes que cambiaron a un tratamiento biológico diferente al anti-TNF, el 62,5% obtuvieron una resolución total o parcial. Discusión La aparición de una reacción paradójica no siempre obliga al cambio de tratamiento biológico, puesto que se ha observado la resolución de las lesiones cutáneas con un tratamiento tópico y/o sistémico adicional en más de la mitad de los pacientes, sin necesidad de suspender el anti-TNF. Si la afectación es grave, se debe plantear el cambio de tratamiento biológico, siendo más eficaz iniciar un fármaco dirigido a una diana terapéutica distinta al anti-TNF (AU)

Presence of Epstein-Barr virus (EBV) antigens detected by sensitive methods has no influence on local immune environment in diffuse large B cell lymphoma.

EBV+ diffuse large B cell lymphoma (DLBCL) not otherwise specified (NOS) is a new entity confirmed by the World Health Organization (WHO) in 2017. In this new entity, the virus may contribute to a tolerogenic microenvironment. Traces of the virus have been described in DLBCL with more sensitive methods, in cases that were originally diagnosed as negative. The aim of this study was to analyze the expression of immune response genes in the tumor microenvironment to disclose the role of the virus and its traces in DLBCL. In 48 DLBCL cases, the expression of immune response genes and the presence of molecules that induce tolerance, such as TIM3, LAG3 and PDL1 by immunohistochemistry (IHC), were studied. To broaden the study of the microenvironment, tumor-associated macrophages (TMAs) were also explored. No significant differences were observed in the expression of immune response genes in the EBV+ DLBCL and those cases that were EBV- DLBCL but that exhibited viral traces, assessed by ViewRNA assay. Only the EBV+ DLBCL cases displayed a significantly higher increase in the expression of CD8 and cytotoxic T cells detected by gene expression analysis, and of PDL1 in tumor cells and in the expression of CD68 in the tumor microenvironment detected by IHC, not observed in those cases with viral traces. The increase in CD8 and cytotoxic T cells, PDL1 and CD68 markers only in EBV+ DLBCL may indicate that traces of viral infection might not have influence in immune response markers.

[Translated article] Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases.

BACKGROUND: Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. MATERIAL AND METHODS: Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. RESULTS: We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. CONCLUSIONS: Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.

Immune-Mediated Skin Reactions to Tumor Necrosis α Inhibitors: A Review of 30 Cases. / Efectos adversos cutáneos inmunomediados por los anti-TNF: revisión de 30 casos.

BACKGROUND: Tumor necrosis factor α (TNF) inhibitors are used to treat different inflammatory diseases. Although these biologics have an adequate safety profile, they have been associated with paradoxical reactions. MATERIAL AND METHODS: Retrospective review of patients on TNF inhibitor therapy who developed a paradoxical skin reaction and were seen at the dermatology department of Hospital Universitari Parc Taulí in Sabadell, Spain. RESULTS: We collected data on 30 patients under treatment with a TNF inhibitor who developed an immune-mediated skin reaction in the form of psoriasis (90%), alopecia (6.7%), or neutrophilic dermatitis (3.3%). The most common drugs involved were adalimumab (56.7%) and infliximab (40%). Psoriasiform reactions mostly manifested as generalized plaques (62.9%) or palmoplantar pustulosis (37%). Thirteen patients (43.3%) continued on the same TNF inhibitor and 12 of them (92.3%) achieved partial or complete resolution of lesions. Five patients were switched to a different TNF inhibitor, but none of them achieved complete resolution. Eight patients were switched to a biologic with a different target, and 5 of them (62.5%) achieved partial or complete resolution. CONCLUSIONS: Paradoxical reactions during TNF inhibitor therapy do not always require a change of treatment. In our series, the addition of a topical and/or systemic treatment resolved the skin lesions in more than half of the patients, and switching to a drug with a different target was more effective. A change of strategy should be contemplated in more serious cases.

Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

Estudio de mortalidad de pacientes en tratamiento con digoxina y trazodona / Study of mortality on patients with digoxin and trazodone treatment

Objetivos: Analizar la influencia de trazodona en la mortalidad de pacientes en tratamiento con digoxina. Material y métodos: Estudio observacional retrospectivo comparativo de mortalidad de pacientes en tratamiento concomitante con digoxina y trazodona versus digoxina. El período de estudio fue de un año (1 de mayo de 2020 hasta 30 de abril de 2021). Las variables recogidas fueron edad, sexo, indicación, dosis de digoxina y trazodona, fecha de inicio de trazodona, fecha fin de digoxina y trazodona, número total de fármacos prescritos, éxitus y fecha de éxitus. El análisis estadístico se realizó mediante la aplicación Stata®. Versión 14.2. Resultados: Se incluyeron 644 pacientes en tratamiento con digoxina, 73 en el grupo con trazodona y 571 en el grupo sin trazodona. Al final del periodo estudiado se registraron 73 muertes, observándose una mortalidad del 34,3% en el grupo de digoxina y trazodona, y del 8,4% en el grupo de digoxina. Las variables relacionadas con el riesgo de muerte fueron tratamiento con tradozona, edad y número de tratamientos prescritos. Conclusiones: Los resultados del estudio sugieren un incremento del riesgo de mortalidad en pacientes de edad avanzada en tratamiento con digoxina y trazodona. La falta de evidencia de uso de trazodona como hipnótico, la interacción farmacocinética entre ambos fármacos y el perfil de seguridad de trazodona, hace necesario una estrecha monitorización de los pacientes o valorar alternativas con mayores evidencias de seguridad.(AU)

Objectives: To evaluate the trazodone influence on the mortality of patients treated with digoxin. Material and methods: Retrospective, observational, comparative study that included patients receiving trazodone and digoxin concomitantly and patients on digoxin treatment without trazodone between April 2020-April 2021. Age, sex, drug indication, digoxin and trazodone dosage, start and end dates of trazodone use, digoxin end date, number of prescribed drugs and death date were the variables we paid attention to. Statistical analysis was performed using the Stata® application. Version 14.2. Results: 644 patients were included, 73 in the group digoxin with trazodone and 571 in the group without trazodone. At the end of the study period, 73 deaths were recorded. Mortality in the digoxin and trazodone group were 34.3% and 8.4% in the digoxin group. The variables related to the risk of death were treatment with trazodone, age and number of prescribed treatments. Conclusions: The results of the study suggest an increased risk of mortality in elderly patients in treated with digoxin and trazodone. The lack of evidence in the use of trazodone as a hypnotic, the pharmacokinetic interaction between both drugs and the safety profile of trazodone, makes it necessary to closely monitor patients or assess therapeutic alternatives with more evidence to be sure its use is safe.(AU)

Expression of two major isoforms of MYO7A in the retina: Considerations for gene therapy of Usher syndrome type 1B.

Usher syndrome type 1B (USH1B) is a deaf-blindness disorder, caused by mutations in the MYO7A gene, which encodes the heavy chain of an unconventional actin-based motor protein. Here, we examined the two retinal isoforms of MYO7A, IF1 and IF2. We compared 3D models of the two isoforms and noted that the 38-amino acid region that is present in IF1 but absent from IF2 affects the C lobe of the FERM1 domain and the opening of a cleft in this potentially important protein binding domain. Expression of each of the two isoforms of human MYO7A and pig and mouse Myo7a was detected in the RPE and neural retina. Quantification by qPCR showed that the expression of IF2 was typically âˆ¼ 7-fold greater than that of IF1. We discuss the implications of these findings for any USH1B gene therapy strategy. Given the current incomplete knowledge of the functions of each isoform, both isoforms should be considered for targeting both the RPE and the neural retina in gene augmentation therapies.

Cost-effectiveness analysis of dyevert™ Power XT in patients with chronic kidney disease undergoing percutaneous coronary intervention procedures in Spain.

OBJECTIVE: To assess the efficiency of Dyevert™ Power XT compared to the standard clinical practice when used for percutaneous coronary interventions (PCI). METHODS: A Markov model was developed to estimate, over 3-month cycles and a lifetime time horizon, the cumulative costs and health outcomes (life years gained [LYG] and quality-adjusted life years [QALY]) in a hypothetical cohort of 1,000 patients with chronic kidney disease (CKD) 3b-4 and an average age of 72 years. The incidence of contrast-induced acute kidney injury for these patients is 18.89% in routine practice and 7.78% with Dyevert. QALYs were estimated by applying utilities by health state. Transitions between states and utilities were obtained from the literature. Overall all-cause and state-specific mortality were considered. The total cost (€2,022) estimated with the National Health System perspective included cost of the procedure and of CKD management. The parameters were validated by a panel of experts. A discount rate (3% per year) was applied to costs and outcomes. RESULTS: The use of Dyevert yielded more health benefits (34.60 LYG and 5.69 QALYs) compared to the current standard practice (33.11 LYG and 5.38 QALYs). Lifetime cost accumulated at the end of the simulation resulted €30,211/patient with Dyevert and €33,895/patient with current standard clinical practice. CONCLUSIONS: The use of Dyevert™ Power XT resulted dominant option, due to its higher effectiveness and lower cost as compared to standard clinical practice and, therefore, a preferred option in patients with CKD stages 3b-4 undergoing PCI in Spain.

Randomized clinical trial on the usefulness of 3D printing in intra-articular fractures of the distal radius. / Ensayo clínico aleatorizado sobre la utilidad de la impresión 3D en las fracturas intraarticulares de radio distal.

OBJECTIVES: We evaluated the utility of 3D printing technology for preoperative planning in the treatment of intra-articular fractures of the distal radius in relation to the improvement of surgical technique, radiological and clinical results. MATERIAL AND METHODS: A total of 30 patients with 2B and C fractures of the AO classification were operated on by a single surgeon with a volar plate, randomly divided into two groups, 15 of them with conventional planning (Rx and CT) and 15 adding a 3D model of the fracture and the previous simulation of the intervention. Simulation time, surgical time in minutes, radioscopy time in minutes, loss of material expressed in lost screws were recorded. Clinical evaluation based PRWE questionnaire and full radiographic analysis was done for all patients with a mean follow-up of 6 months by an independent, blinded observed. RESULTS: No statistically significant differences were observed in the PRWE questionnaire (p=0.22), nor were we observed differences in the radiological values, except in relation to the articular step (p=0.028), which represents statistical significance, but in both groups the median was of 0.0 (0.0-0.0). We also did not see statistically significant differences in surgical times (p=0.745), radioscopy (p=0.819) or in the loss of synthesis material (p=0.779). CONCLUSIONS: 3D printing has not improved the parameters studied in relation to routinely operated patients.

Educación, ejercicio terapéutico y terapia manual en el dolor orofacial. Estudio de casos / Education, therapeutic exercise, and manual therapy approaches in orofacial pain. Case reports

Introducción Los trastornos temporomandibulares son la causa más común de dolor crónico orofacial. Intervenciones pasivas como la terapia manual (TM) es de las herramientas más utilizadas. Sin embargo, este tipo de abordajes puede resultar insuficiente. La investigación de nuevas estrategias, ahora de naturaleza activa, como son el ejercicio o la educación, es necesaria para generar un cambio en la práctica clínica de los profesionales sanitarios y brindar una atención completa al paciente con dolor crónico. Objetivos Analizar el efecto de tres abordajes principales de forma combinada sobre el dolor, factores psicosociales, variables funcionales y biomecánicas. Métodos Se siguió un diseño de estudio de casos compuesto por tres sujetos divididos en tres modelos de intervención: educación para el dolor y terapia manual (PEdu+TM), ejercicio terapéutico y terapia manual (PEjerc+TM) y terapia manual cervical y orofacial (PTM). El periodo de intervención duró 3-4 semanas; las medidas fueron tomadas en tres momentos: preintervención, postintervención inmediata y 45 días postintervención. Dolor, características psicosociales y funcionalidad del paciente fueron evaluadas con diferentes herramientas validadas. Resultados Los resultados mostraron a corto plazo una mejora en todas las variables analizadas en el PEdu+TM y en el PEjerc+TM, pero no en el PTM. A medio plazo (45 días postintervención), el PEdu+TM mostró beneficios en todas las variables estudiadas mientras que el PEjerc+TM generó cambios positivos en las mismas variables excluyendo el dolor. Conclusión El tratamiento combinado podría ser una intervención más eficaz que la terapia manual a solas, siendo necesarios ensayos clínicos aleatorizados que corroboren dichos hallazgos (AU)

Introduction Temporomandibular disorders are the most common cause of chronic orofacial pain. Passive interventions such us manual therapy (MT) is being one of the most used tools. However, this type of approach may be insufficient. The investigation of new strategies, now of an active nature such as exercise or education, it is necessary to generate a change in the clinical practice of health professionals and provide comprehensive care to patients with chronic pain. Objectives To analyze the effect of three main approaches in combination on pain, psychosocial factors, functional and biomechanical variables. Methods A case study design was followed consisting of three subjects divided into three intervention models: pain education and manual therapy (PEdu+TM), therapeutic exercise and manual therapy (PExer+TM), and cervical and orofacial manual therapy (PTM). The intervention period lasted 3-4 weeks, the measurements were taken at three moments: pre-intervention, immediate post-intervention and 45 days post-intervention. Pain, psychosocial characteristics and functionality of the patient were evaluated with different validated tools. Results The results showed in the short-term an improvement in all the variables analyzed in the PEdu+TM and in the PExer+TM, but not in the PTM. In the medium term (45 days post-intervention), the PEdu+TM showed benefits in all the variables studied, while the PExer+TM generated positive changes in the same variables, excluding pain. Conclusion Combined treatment could be a more effective intervention than manual therapy alone, requiring randomized clinical trials to corroborate these findings (AU)

Single-cell transcriptome analysis of xenotransplanted human retinal organoids defines two migratory cell populations of nonretinal origin.

Human retinal organoid transplantation could potentially be a treatment for degenerative retinal diseases. How the recipient retina regulates the survival, maturation, and proliferation of transplanted organoid cells is unknown. We transplanted human retinal organoid-derived cells into photoreceptor-deficient mice and conducted histology and single-cell RNA sequencing alongside time-matched cultured retinal organoids. Unexpectedly, we observed human cells that migrated into all recipient retinal layers and traveled long distances. Using an unbiased approach, we identified these cells as astrocytes and brain/spinal cord-like neural precursors that were absent or rare in stage-matched cultured organoids. In contrast, retinal progenitor-derived rods and cones remained in the subretinal space, maturing more rapidly than those in the cultured controls. These data suggest that recipient microenvironment promotes the maturation of transplanted photoreceptors while inducing or facilitating the survival of migratory cell populations that are not normally derived from retinal progenitors. These findings have important implications for potential cell-based treatments of retinal diseases.

Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice.

Many patients with diabetic eye disease respond inadequately to anti-VEGF therapies, implicating additional vasoactive mediators in its pathogenesis. We demonstrate that levels of angiogenic proteins regulated by HIF-1 and -2 remain elevated in the eyes of people with diabetes despite treatment with anti-VEGF therapy. Conversely, by inhibiting HIFs, we normalized the expression of multiple vasoactive mediators in mouse models of diabetic eye disease. Accumulation of HIFs and HIF-regulated vasoactive mediators in hyperglycemic animals was observed in the absence of tissue hypoxia, suggesting that targeting HIFs may be an effective early treatment for diabetic retinopathy. However, while the HIF inhibitor acriflavine prevented retinal vascular hyperpermeability in diabetic mice for several months following a single intraocular injection, accumulation of acriflavine in the retina resulted in retinal toxicity over time, raising concerns for its use in patients. Conversely, 32-134D, a recently developed HIF inhibitor structurally unrelated to acriflavine, was not toxic to the retina, yet effectively inhibited HIF accumulation and normalized HIF-regulated gene expression in mice and in human retinal organoids. Intraocular administration of 32-134D prevented retinal neovascularization and vascular hyperpermeability in mice. These results provide the foundation for clinical studies assessing 32-134D for the treatment of patients with diabetic eye disease.

Brain system segregation and pain catastrophizing in chronic pain progression.

Pain processing involves emotional and cognitive factors that can modify pain perception. Increasing evidence suggests that pain catastrophizing (PC) is implicated, through pain-related self-thoughts, in the maladaptive plastic changes related to the maintenance of chronic pain (CP). Functional magnetic resonance imaging (fMRI) studies have shown an association between CP and two main networks: default mode (DMN) and dorsoattentional (DAN). Brain system segregation degree (SyS), an fMRI framework used to quantify the extent to which functional networks are segregated from each other, is associated with cognitive abilities in both healthy individuals and neurological patients. We hypothesized that individuals suffering from CP would show worst health-related status compared to healthy individuals and that, within CP individuals, longitudinal changes in pain experience (pain intensity and affective interference), could be predicted by SyS and PC subdomains (rumination, magnification, and helplessness). To assess the longitudinal progression of CP, two pain surveys were taken before and after an in-person assessment (physical evaluation and fMRI). We first compared the sociodemographic, health-related, and SyS data in the whole sample (no pain and pain groups). Secondly, we ran linear regression and a moderation model only in the pain group, to see the predictive and moderator values of PC and SyS in pain progression. From our sample of 347 individuals (mean age = 53.84, 55.2% women), 133 responded to having CP, and 214 denied having CP. When comparing groups, results showed significant differences in health-related questionnaires, but no differences in SyS. Within the pain group, helplessness (ß = 0.325; p = 0.003), higher DMN (ß = 0.193; p = 0.037), and lower DAN segregation (ß = 0.215; p = 0.014) were strongly associated with a worsening in pain experience over time. Moreover, helplessness moderated the association between DMN segregation and pain experience progression (p = 0.003). Our findings indicate that the efficient functioning of these networks and catastrophizing could be used as predictors of pain progression, bringing new light to the influence of the interplay between psychological aspects and brain networks. Consequently, approaches focusing on these factors could minimize the impact on daily life activities.

Coloides perioperatorios: de la teoría a la práctica / Perioperative colloids: From theory to practice

Introducción: La administración intravenosa de fluidos constituye un elemento fundamental en la reanimación de pacientes con hipovolemia. Las guías clínicas restringen el uso de coloides en favor de los cristaloides. Actualmente, no conocemos con exactitud cuál es la práctica clínica habitual al respecto durante el periodo perioperatorio. El objetivo del presente estudio es describir el uso perioperatorio de coloides y analizar las posibles causas que motivan su utilización. Material y métodos: Estudio observacional, transversal, multicéntrico. Subanálisis del estudio Fluid Day. Se incluyeron todos los pacientes mayores de 18 años sometidos a cirugía durante las 24h de los 2 días del estudio (18 y 20 de febrero de 2019). Se registraron datos demográficos, comorbilidades, datos referentes al acto anestésico y el procedimiento quirúrgico, fluidos administrados, sangrado perioperatorio y tipo de monitorización utilizado durante el periodo perioperatorio. Resultados: Se analizaron 5.928 casos. Un total de 542 pacientes (9,1%) recibieron algún tipo de coloides, siendo el hidroxietilalmidón el más utilizado (5,1%). Los pacientes que recibieron coloides tuvieron intervenciones más prolongadas (150 [90-255] vs. 75 [45-120] min), fueron intervenidos de urgencia (13,7 vs. 7,5%) y se clasificaron como de alto riesgo (22 vs. 4,8%) más frecuentemente. Su recuperación inmediata mayoritariamente transcurrió en unidades de críticos (45,1 vs.15,8%). Los pacientes que presentaron una hemorragia menor de 500ml recibieron coloides en un 5,9% frente al 45,9% cuando se superó esta cifra. Los pacientes que recibieron coloides presentaban anemia más frecuentemente: 29,4 vs. 16,3%. La administración de coloides supuso un mayor riesgo de transfusión (OR 15,7). La monitorización avanzada también aumentó la probabilidad de administrar coloides (OR 9,43). Conclusiones: En nuestro medio y en condiciones de práctica clínica habitual, la utilización de los coloides es escasa...(AU)

Introduction: Fluid administration is the cornerstone in hypovolemic patient's reanimation. Clinical guidelines restrict colloid administration favouring crystalloids. Currently, we don’t know exactly which is the daily clinical practice during the perioperative period. The objective of this study is to describe perioperative use of colloids analysing possible reasons aiming to use them. Material and Methods: Prospective, cross-section, national, multicentre observational study. Fluid Day sub-study. We enrolled all patient's older than 18 years old who underwent surgery during the 24h of the 2-days study (February, 2019, 18th and 20th). We registered demographic data, comorbidities, anaesthetic and surgical procedure data, fluids administered, perioperative bleeding and monitoring type used during the perioperative period. Results: A total of 5928 cases were analysed and 542 patients (9.1%) received any type of colloids, being hydroxiethyl-starch the most frequently used (5.1%). Patients receiving colloids suffered more longing surgery (150 [90-255] vs. 75 [45-120] min), were urgently operated (13.7 vs. 7.5%) and were more frequent classified as high risk (22 vs. 4.8%). Their recovery was mostly in critical care units (45.1 vs.15.8%). Patients with bleeding less than 500mL received colloids in a percentage of 5.9 versus 45.9% when this figure was overcome. Patients who received colloids were anaemic more frequently: 29.4 vs. 16.3%. Colloids administration had a higher risk for transfusion (OR 15.7). Advanced monitoring also increased the risk for receiving colloids (OR 9.43). Conclusions: In our environment with routine clinical practice, colloids administration is limited and close linked to perioperative bleeding.(AU)

Perioperative colloids: From theory to practice.

INTRODUCTION: Fluid administration is the cornerstone in hypovolemic patient's reanimation. Clinical guidelines restrict colloid administration favouring crystalloids. Currently, we don't know exactly which is the daily clinical practice during the perioperative period. The objective of this study is to describe perioperative use of colloids analysing possible reasons aiming to use them. MATERIAL AND METHODS: Prospective, cross-section, national, multicentre observational study. Fluid Day sub-study. We enrolled all patient's older than 18 years old who underwent surgery during the 24 h of the 2-days study (February, 2019, 18th and 20th). We registered demographic data, comorbidities, anaesthetic and surgical procedure data, fluids administered, perioperative bleeding and monitoring type used during the perioperative period. RESULTS: A total of 5928 cases were analysed and 542 patients (9.1%) received any type of colloids, being hydroxiethyl-starch the most frequently used (5.1%). Patients receiving colloids suffered more longing surgery (150 [90-255] vs. 75 [45-120] min), were urgently operated (13.7 vs. 7.5%) and were more frequent classified as high risk (22 vs. 4.8%). Their recovery was mostly in critical care units (45.1 vs.15.8%). Patients with bleeding less than 500 ml received colloids in a percentage of 5.9 versus 45.9% when this figure was overcome. Patients who received colloids were anaemic more frequently: 29.4 vs. 16.3%. Colloids administration had a higher risk for transfusion (OR 15.7). Advanced monitoring also increased the risk for receiving colloids (OR 9.43). CONCLUSIONS: In our environment with routine clinical practice, colloids administration is limited and close linked to perioperative bleeding.