Measurement assessment of Minimal Disease Activity in psoriasis in Spain: a national cross-sectional study. / Valoración de la medida de Actividad Mínima de Enfermedad en Psoriasis en España: estudio transversal nacional.

INTRODUCTION: in 2017, the Spanish Academy of Dermatology and Venereology Psoriasis Working Group (PWG) designed the Minimal Disease Activity (MDA) criteria to determine the level of disease activity. We hereby present the results of an observational, cross-sectional, multicenter study of the nationwide application of these criteria. MATERIAL AND METHODS: we conducted a non-randomized sampling, stratified to achieve autonomic and provincial representation of consecutive patients with psoriasis (Ps) vulgaris without active arthritis. A total of 830 patients were included: 493 men (59.5%), with a mean age of 51.4 years (SD, 14.2), from all autonomous regions of Spain (except for Ceuta and Melilla) and 44 (88%) out of the 50 provinces. A questionnaire was obtained with demographic data, DLQI, subjective assessment-on a scale from 0 to 10-of itching, erythema, desquamation, visibility, and the patients' PASI and BSA. RESULTS: more than 50% failed to meet the MDA criteria (491; 59.2%), with significant differences being reported by region, sex, and age. Additionally, significant differences were reported based on the therapy used (p < 0.001). The use of biological therapies was associated with higher MDA compliance compared to other therapies (59.4% vs 23.3%). No differences were reported among various biological therapies. CONCLUSIONS: the overall rate of MDA compliance is low, with differences being based on geographic location, sex, age, and drug used, yet none of these factors separately justify them.

Uncovering the neural control of laryngeal activity and subglottic pressure in anaesthetized rats: insights from mesencephalic regions.

To assess the possible interactions between the dorsolateral periaqueductal gray matter (dlPAG) and the different domains of the nucleus ambiguus (nA), we have examined the pattern of double-staining c-Fos/FoxP2 protein immunoreactivity (c-Fos-ir/FoxP2-ir) and tyrosine hydroxylase (TH) throughout the rostrocaudal extent of nA in spontaneously breathing anaesthetised male Sprague-Dawley rats during dlPAG electrical stimulation. Activation of the dlPAG elicited a selective increase in c-Fos-ir with an ipsilateral predominance in the somatas of the loose (p < 0.05) and compact formation (p < 0.01) within the nA and confirmed the expression of FoxP2 bilaterally in all the domains within the nA. A second group of experiments was made to examine the importance of the dlPAG in modulating the laryngeal response evoked after electrical or chemical (glutamate) dlPAG stimulations. Both electrical and chemical stimulations evoked a significant decrease in laryngeal resistance (subglottal pressure) (p < 0.001) accompanied with an increase in respiratory rate together with a pressor and tachycardic response. The results of our study contribute to new data on the role of the mesencephalic neuronal circuits in the control mechanisms of subglottic pressure and laryngeal activity.

[Synthetic indicator of compliance with standards for Quality Units of health centers and multicenter prospective pilot study]. / Indicador sintético de cumplimiento de estándares para Unidades de Calidad de centros sanitarios y estudio de pilotaje prospectivo multicéntrico.

BACKGROUND AND OBJECTIVE: In Spain, Quality Units play a key and unique role in advising healthcare centers on the methodology of healthcare quality. The objectives of the study were to develop computer algorithms to obtain a synthetic indicator of standard compliance for Quality Units and to pilot its functioning in these units. MATERIALS AND METHODS: The Excel program was used to establish evaluation algorithms, and quantitatively interrelate and weight various categories of standards, as a computer evaluation tool, to build a continuous improvement cycle system, and offer a global synthetic indicator of compliance. The tool was tested in a prospective multicenter pilot study, in which coordinators of Quality Units from different health centers and care settings participated, to evaluate the usefulness of the tool and compliance with the standards, in addition to analyzing the content validity of each standard. RESULTS: The formulas for the structured computer algorithms were developed, consecutively, in a «PLAN-DO-CHECK-ACT¼ improvement cycle for the 9 categories of standards, resulting in a single synthetic indicator of compliance. Twenty-one Quality Units participated in the piloting. The overall average compliance rate for the synthetic indicator was 55.63% with differences between centers (P=.002) and between categories (P<.0001), but not by autonomous communities (P=.86) or by areas (P=.97). Content validity was ensured through the variable of «understanding¼ of the standards (P<.001), and through their «justification¼ with documentary evidence (P<.001). CONCLUSIONS: The computer tool with the synthetic indicator have allowed for the evaluation of standard compliance in Quality Units of healthcare centers.

Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas. / [Artículo traducido] Experiencia con bexaroteno en linfoma cutáneo de células T: un estudio del Grupo Español de Linfomas Cutáneos (GELC).

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

Real-world Safety and Efficacy of Risankizumab in Psoriatic Patients: A Multicenter, Retrospective, and Not-interventional Study.

BACKGROUND AND OBJECTIVE: Risankizumab - a humanized monoclonal antibody that targets the p19 subunit of IL-23 - has been recently approved to treat moderate-to-severe plaque psoriasis. Real-world data based on a representative pool of patients are currently lacking. OBJECTIVE: To assess the mid- and long-term safety and efficacy profile of risankizumab in patients with moderate-to-severe psoriasis in the routine clinical practice. METHODS: This was a retrospective and multicenter study of consecutive psoriatic patients on risankizumab from April 2020 through November 2022. The primary endpoint was the number of patients who achieved a 100% improvement in their Psoriasis Area and Severity Index (PASI) (PASI100) on week 52. RESULTS: A total of 510 patients, 198 (38.8%) women and 312 (61.2%) men were included in the study. The mean age was 51.7±14.4 years. A total of 227 (44.5%) study participants were obese (body mass index [BMI] >30kg/m2). The mean baseline PASI score was 11.4±7.2, and the rate of patients who achieved PASI100 on week 52, 67.0%. Throughout the study follow-up, 21%, 50.0%, 59.0%, and 66% of the patients achieved PASI100 on weeks 4, 16, 24, and 40, respectively. The number of patients who achieved a PASI ≤2 was greater in the group with a BMI ≤30kg/m2 on weeks 4 (P=.04), 16 (P=.001), and 52 (P=.002). A statistically significantly greater number of patients achieved PASI100 in the treatment-naïve group on weeks 16 and 52 (P=.001 each, respectively). On week 16 a significantly lower number of participants achieved PASI100 in the group with psoriatic arthropathy (P=.04). Among the overall study sample, 22 (4.3%) patients reported some type of adverse event and 20 (3.9%) discontinued treatment. CONCLUSIONS: Risankizumab proved to be a safe and effective therapy for patients with moderate-to-severe psoriasis in the routine clinical practice.

Formation of intraneuronal iron deposits following local release from nanostructured silica injected into rat brain parenchyma.

Nanostructured materials with controllable properties have been used to cage and release various types of compounds. In the present study, iron-loaded nanostructured sol-gel SiO2-Fe materials were prepared and injected into the rat brain to develop a method for gradual iron delivery into the neurons with the aims to avoid acute iron toxicity and develop an animal model of gradual, metal-induced neurodegeneration. Nanoparticles were prepared by the traditional method of hydrolysis and condensation reactions of tetraethyl orthosilicate at room temperature and subsequent heat treatment at 200 °C. FeSO4 was added in situ during the silica preparation. The resulting materials were characterized by UV-VIS and infrared spectroscopies, X-ray diffraction, and N2 adsorption-desorption. An in vitro ferrous sulfate release test was carried out in artificial cerebrospinal fluid as the release medium showing successful ferrous sulfate loading on nanostructured silica and sustained iron release during the test time of 10 h. Male Wistar rats administered with SiO2-Fe nanoparticles in the substantia nigra pars compacta (SNpc) showed significant intraneuronal increase of iron, in contrast to the animals administered with FeSO4 that showed severe neuronal loss, 72 h post-treatment. Both treatments induced lipid fluorescent product formation in the ventral midbrain, in contrast to iron-free SiO2 and PBS-only injection controls. Circling behavior was evaluated six days after the intranigral microinjection, considered as a behavioral end-point of brain damage. The apomorphine-induced ipsilateral turns in the treated animals presented significant differences in relation to the control groups, with FeSO4 administration leading to a dramatic phenotype, compared to a milder impact in SiO2-Fe administrated animals. Thus, the use of SiO2-Fe nanoparticles represents a slow iron release system useful to model the gradual iron-accumulation process observed in the SNpc of patients with idiopathic Parkinson's disease.

Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas.

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

Comparing the Use of Topical Therapy Along with Anti-IL-17 and Anti-IL-23 to Treat Moderate-to-Severe Psoriasis in the Routine Clinical Practice. / Comparación del uso de la terapia tópica combinada con anti-interleucina-17 y anti-interleucina-23 en la psoriasis moderada grave en la práctica clínica.

BACKGROUND: Combinations of topical (TT) and biological therapies (BT) are a common thing in the routine clinical practice. However, the scientific medical literature on how TT is, actually, used after the initiation of BT is scarce, particularly in combination with anti-IL17, or anti-IL23. OBJECTIVES: To describe the frequency of the concomitant use of TT + BT at baseline and after a 6-month course of several drugs (anti-IL17, ustekinumab, and anti-IL23). Our secondary endpoints are to describe the type of topical therapy used, compare the frequency of use of TT among the different groups of BT, describe the survival of topical therapy in these patients, and identify the factors that can impact the use or discontinuation of topical therapy in these patients (clinical response, quality of life, type of drug, etc.). MATERIALS AND METHODS: This was a retrospective, observational, and single-center study of patients with moderate-to-severe psoriasis treated with anti-IL17 (secukinumab, ixekizumab), anti-IL17R (brodalumab), ustekinumab, and guselkumab from January 2015 through December 2020. RESULTS: We included a total of 138 patients. When treatment started, 82.7% were on TT (55% daily), and after 6 months, 86.6% had discontinued TT. Regarding the analysis by type of drug, at 6 months, we found that 100% of the patients with BRO had discontinued topical treatment. We did not find any significant differences in the frequency of use of TT based on the BT used during the 6-month course of treatment. The estimated mean course of TT was 4.3 months (SD, 6.7). Also, the estimated mean course of TT was significantly shorter in the group of patients who achieved PASI100 (2.8 months vs. 8.1 months). CONCLUSIONS: In our cohort, we saw a significant decrease in the frequency of use of TT at 6 months after starting BT in the routine clinical practice. This reduction occurred earlier in patients who improved their objective clinical response and quality of life.

Family Planning Concerns Among Women With Psoriasis: A Descriptive, Cross-Sectional, Multicenter Study. / Percepción de la mujer con psoriasis en la planificación familiar: Estudio descriptivo, transversal y multicéntrico.

BACKGROUND AND OBJECTIVE: A significant proportion of women of childbearing age have psoriasis. The aim of this study was to examine family planning concerns in this population. MATERIAL AND METHODS: Observational, descriptive, cross-sectional, multicenter study conducted between March 2020 and October 2021. We collected sociodemographic data and analyzed responses to a family planning questionnaire administered to women aged 18 to 45 years with plaque psoriasis who were candidates for systemic treatment. RESULTS: We studied 153 patients (mean [SD] age, 35.4 [8.0] years; mean disease duration, 16.7 years) being treated at 11 Spanish hospitals. Overall, 38.4% of women were considered to have moderate to severe psoriasis by their physicians; perceived severity ratings were significantly higher among women. Psoriasis affected the women's desire to become pregnant or led to their delaying pregnancy in 1 in 3 respondents. They were concerned that their condition might worsen if they had to discontinue or switch treatment or that the treatment might harm the baby. Approximately half of the women had not received family planning counseling from their physicians, and this was more likely to be the case among never-pregnant women. Women on biologic therapy (58.7%) had better psoriasis control and a better quality of life than women on other treatments. Their sexual health was also less affected. CONCLUSIONS: Women with psoriasis have numerous family planning concerns, which in some cases can lead them to delay pregnancy or affect their desire to become pregnant. Dermatologists need to receive better training regarding family planning in women with psoriasis so that they can provide their patients with more and better information.

[Neurological evolution in traumatic spinal cord injury according to the size of the intraparenchymal hemorrhage]. / Evolución neurológica en la lesión medular traumática en función del tamaño de la hemorragia intraparenquimatosa.

INTRODUCTION AND OBJECTIVES: The presence of spinal cord hemorrhage is considered as a poor prognostic factor in traumatic spinal cord injury (SCI). However, it has been suggested in published works that the prognosis of small hemorrhages is not so negative. The aim of this paper is to assess the neurological evolution in individuals with intraparenchymal hemorrhage according to its size. MATERIAL AND METHODS: Retrospective observational study. Selected all the patients admitted for acute traumatic SCI between 2010 and 2018 with early magnetic resonance study and spinal cord hemorrhage. Two groups were established depending on the size of the bleeding: microhemorrhages (less than 4mm) and macrohemorrhages (greater than 4mm). The neurological examination at admission and discharge was compared according to the AIS grade and the motor score (MS). RESULTS: Forty-six cases collected, 17 microhemorrhages and 29 macrohemorrhages. 70.6% of the microhemorrhages were AIS A while among macrohemorrhages the percentage was 89.6%. At the time of discharge, an improvement in the AIS grade was observed in 40.0% of the microhemorrhages compared to 4.0% of the macrohemorrhages (P=.008). Initial MS was similar, 45.2±22.2 in the microhemorrhages and 40.9±20.4 in the macrohemorrhages (P=.459), but at discharge it was higher in the first group: 60.4±20.5 for 42.7±22.8 (P=.033). Eight patients (17.4%) died during admission. CONCLUSIONS: There is a relationship between the size of the intraparenchymal hemorrhage and the neurological prognosis of SCI, with hemorrhages smaller than 4mm presenting a better evolution.

[Translated article] Family Planning Concerns Among Women With Psoriasis: A Descriptive, Cross-Sectional, Multicenter Study.

BACKGROUND AND OBJECTIVE: A significant proportion of women of childbearing age have psoriasis. The aim of this study was to examine family planning concerns in this population. MATERIAL AND METHODS: Observational, descriptive, cross-sectional, multicenter study conducted between March 2020 and October 2021. We collected sociodemographic data and analyzed responses to a family planning questionnaire administered to women aged 18 to 45 years with plaque psoriasis who were candidates for systemic treatment. RESULTS: We studied 153 patients (mean [SD] age, 35.4 [8.0] years; mean disease duration, 16.7 years) being treated at 11 Spanish hospitals. Overall, 38.4% of women were considered to have moderate to severe psoriasis by their physicians; perceived severity ratings were significantly higher among women. Psoriasis affected the women's desire to become pregnant or led to their delaying pregnancy in 1 in 3 respondents. They were concerned that their condition might worsen if they had to discontinue or switch treatment or that the treatment might harm the baby. Approximately half of the women had not received family planning counseling from their physicians, and this was more likely to be the case among never-pregnant women. Women on biologic therapy (58.7%) had better psoriasis control and a better quality of life than women on other treatments. Their sexual health was also less affected. CONCLUSIONS: Women with psoriasis have numerous family planning concerns, which in some cases can lead them to delay pregnancy or affect their desire to become pregnant. Dermatologists need to receive better training regarding family planning in women with psoriasis so that they can provide their patients with more and better information.

Transdiagnostic inflammatory and oxidative biomarkers with predictive capacity of self-injurious behavior in impulsive and unstable disorders.

INTRODUCTION: Alterations in inflammatory processes have previously been reported in impulsive and unstable disorders, as well as in other psychiatric conditions. In order to investigate transdiagnostic biomarkers associated with various phenotypic features of these disorders, this study is designed to identify biomarkers of inflammatory and oxidative endophenotypes related to autolytic behavior. METHODS: Peripheral blood mononuclear cells were collected from 35 patients with borderline personality disorder (BPD), 29 patients with restrictive eating disorder (rED), 21 patients with purging eating disorder (pED) and 23 control subjects. Plasma levels of different inflammatory and oxidative factors were measured by ELISA and the expression of selected proteins was by Western Blot. Principal component analysis (PCA) was performed to categorize the different inflammatory factors. Additionally, Ancova was performed to observe the differences in the principal components among the different groups and logistic regression analysis was conducted to assess the predictive capacity of these components for autolytic behaviors. RESULTS: We found two inflammatory/oxidative components were associated with BPD, characterized by high levels of JNK and ERK and low levels of GPx, SOD and Keap1; and two other inflammatory/oxidative components were linked to pED, associated with more JNK, TBARS and TNF-α and less GPx and SOD. Two components, with more JNK and ERK and less GPx, SOD and Keap1, predicted non-suicidal self-injury and three components, with higher JNK, TBARS and TNF-α levels and lower GPx, SOD and iNOS levels, predicted suicide attempts. CONCLUSIONS: These results strongly support the endophenotypic characterization of impulsivity and the identification of transdiagnostic inflammatory/oxidative biomarkers relevant to autolytic behavior in impulsive and unstable disorders. These dates lay the groundwork for developing of screening tests for these biomarker components to rapidly detect biological risk factors for specific impulse control disorders and future self-injurious behaviors.

Decreased oxytocin plasma levels and oxytocin receptor expression associated with aggressive behavior in aggressive-impulsive disorders.

INTRODUCTION: This study aims to enhance the understanding of the association between the phenotypic and endophenotypic characteristics of impulsive-aggressive disorders, through the study of plasma oxytocin (OXT) and oxytocin receptor (OXTR) levels in patients with borderline personality disorder (BPD) and patients with eating disorders (ED), as well as to examine the relationship of OXT system with aggressive behavior in these disorders. METHODS: 68 patients with BPD, 67 patients with ED and 57 healthy control subjects were examined for plasma oxytocin levels and protein expression of OXTR in blood mononuclear cells. Aggressive behavior was assessed using the State-Trait Anger Expression Inventory (STAXI-2). Other self and hetero-aggressive behaviors were also evaluated through interviews. RESULTS: BPD and ED patients exhibited significantly lower plasma oxytocin levels than control subjects. Furthermore, BPD patients demonstrated significantly reduced expression of OXTR compared to controls. Plasma oxytocin levels negatively correlated with verbal aggression, while OXTR expression was inversely associated with the STAXI trait subscale. CONCLUSIONS: The findings validate the existence of oxytocin system dysfunction in impulsive-aggressive disorders. They also support the link between low OXT levels in plasma and OXTR expression and the impulsive-aggressive behavior that characterizes these patients in both state and trait situations.

Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real-life clinical practice.

BACKGROUND: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. OBJECTIVE: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. METHODS: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. RESULTS: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. CONCLUSION: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.

[Development and validation of standards for quality units of health centers]. / Desarrollo y validación de estándares para unidades de calidad de centros sanitarios.

OBJECTIVE: In Spain, the Quality Units advise health centres, services and professionals on the methodology of continuous improvement of the quality of care. A system based on good practice standards could provide these units with a tool to improve their results and value their work. The objective was to develop, agree on and validate standards, to properly guide and orient the functions, results and continuous improvement of the Quality Units in health centers. MATERIAL AND METHODS: A qualitative-quantitative, prospective and cross-sectional study was carried out, applying the Metaplan method, the e-Delphi technique and a simulation study. The participants were coordinators of these units, belonging to 14 Spanish Autonomous Communities and distributed in four experts' panels. They agreed on the standards to be used and evaluated the different types of validity. RESULTS: The 204 standards proposed by the scientific committee were reduced to 157 with Metaplan, to 110 with e-Delphi, and to 96 with the committee's final review (87.3% consensus, content validity). The construct validity showed a Cronbach's alpha >0.7 (P<.001); the validity of content was reaffirmed in the simulation workshop (80% "understood" each other, P<.001; and there was "documentary evidence" in 84%, P<.001); face validity was accepted (75% "related to quality dimensions", P<.001); and the validity of the criteria was verified with a sensitivity of 84.2%, a specificity of 98.3%, and a kappa index of 0.84. CONCLUSIONS: Valid standards have been developed for Quality Units in health centers.