Do NPM1 and FLT3-ITD mutations modify prognosis in patients treated with non-intensive regimens?

FLT3-ITD and NPM1 mutations are key to defining the genetic risk profile of acute myeloid leukemia (AML). We aimed to assess the prognostic features of the FLT3-ITD and NPM1 mutations in old and/or unfit individuals with AML treated with non-intensive therapies in the era before azacitidine-venetoclax approbation. The results of various non-intensive regimens were also compared. We conducted a retrospective analysis that included patients treated with different non-intensive regimens, between 2007 and 2020 from PETHEMA AML registry. We compiled 707 patients with a median age of 74 years and median follow-up time of 37.7 months. FLT3-ITD patients (N = 98) showed a non-significant difference in overall survival (OS) compared to FLT3-ITD negative-patients (N = 608) (P = 0.17, median OS was 5 vs 7.3 months respectively). NPM1-mutated patients (N = 144) also showed a non-significant difference with NPM1 wild type (N = 519) patients (P = 0.25, median OS 7.2 vs 6.8 respectively). In the Cox regression analysis neither NPM1 nor FLT3-ITD nor age were significant prognostic variables for OS prediction. Abnormal karyotype and a high leukocyte count showed a statistically significant deleterious effect. Azacitidine also showed better survival compared to FLUGA (low dose cytarabine plus fludarabine). NPM1 and FLT3-ITD seem to lack prognostic value in older/unfit AML patients treated with non-intensive regimens other than azacitidine-venetoclax combination.

Efficacy of omalizumab for the treatment of bullous pemphigoid: Spanish multicentre real-world experience.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Most patients are older and have associated multiple comorbidities. Topical and systemic corticosteroids are considered the first-line treatment for BP, and immunosuppressants are used as steroid-sparing treatments. However, both have side-effects and contraindications, which are even more common in this older population. New treatments targeting interleukins and receptors related to BP pathogenesis have been proposed to decrease these side-effects while achieving equal or better effectiveness and response rates. Omalizumab is a monoclonal antibody that targets IgE and has been proposed for the treatment of BP due to the evidence that IgE autoantibodies play an essential role in BP pathogenesis. OBJECTIVES: To assess the efficacy and safety of omalizumab for the treatment of BP. METHODS: We carried out a multicentre, retrospective, observational study including patients diagnosed with BP who received omalizumab for ≥ 3 months from 15 tertiary hospitals in Spain. IgE levels prior to treatment were measured, and we evaluated the possible correlation with clinical response. We excluded patients treated with omalizumab for < 3 months, as we consider this duration to be insufficient for a comprehensive assessment of its efficacy. To evaluate the effectiveness of the treatment, we used the percentage of body surface area improvement. RESULTS: We included 36 patients. The vast majority had associated multiple comorbidities, and all patients had used other systemic therapies apart from corticosteroids before omalizumab. In total, 83% experienced some kind of treatment response and 42% of all patients treated achieved complete response. We did not find any correlation between higher IgE levels and a better response (P = 0.2). All patients tolerated omalizumab without reported side-effects. CONCLUSIONS: Omalizumab is a good therapeutic alternative for BP as it provided clinical response in most patients, and nearly one-half of the cases achieved complete response. It showed no side-effects, which is crucial in older patients with BP.

Real-world experience of secukinumab dose optimization in moderate-to-severe psoriasis. Retrospective, single-center series of 11-patients. / Experiencia en la práctica clínica tras la optimización de la dosis del secukinumab en la psoriasis moderada-severa. Serie retrospectiva de 11 casos.

Psoriasis is a chronic immune-mediated inflammatory systemic disease that mainly affects skin. Secukinumab is an anti-interleukin-17A agent approved for the treatment of moderate-to-severe psoriasis that has probed efficacy and safety both in clinical trials and in real-world practice. Secukinumab data sheet dose approved in maintenance response phase for adults with psoriasis is 300mg monthly. Recently, dose optimization for biologic therapies in psoriasis has been proposed in order to individualise the treatment looking for better treatment adherence and better cost-effectiveness due to their high costs. In this scenario, we report our real-world experience in dose optimization for patients with moderate-to-severe psoriasis treated with Secukinumab.

52-Week Mid-term Efficacy of Tildrakizumab in Moderate-to-severe Psoriasis: A Real-life Multicenter Experience. / [Artículo traducido] Eficacia a medio plazo (52 semanas) de tildrakizumab en el tratamiento de la psoriasis moderada a severa: un estudio multicéntrico de práctica clínica.

Tildrakizumab is an IL-23-inhibitor that has been approved to treat plaque psoriasis. However, few reports have become available on its efficacy profile in the real-world. Our objective was to study the mid-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the Spanish routine clinical practice setting. This was a retrospective multicenter study that included a total of 91 psoriatic patients on tildrakizumab. The mean Psoriasis Area and Severity Index (PASI) was 9.09 (SD, 5.30). The overall tildrakizumab survival rate was 93.47% for a mean treatment exposure of 30.18 weeks (SD, 16.57). No drug discontinuation was associated with drug tolerability, or adverse reactions. Absolute PASI ≤3 was reached by 91.3% and 96.5% of the patients on weeks 28 and 52, respectively. Response was not impacted by weight, age (>65), metabolic syndrome, presence of arthritis, or previous number of biological therapies used. Based on our own experience tildrakizumab is an effective strategy to treat plaque psoriasis and difficult-to-treat-areas.

52-Week Mid-term Efficacy of Tildrakizumab in Moderate-to-severe Psoriasis: A Real-life Multicenter Experience.

Tildrakizumab is an IL-23-inhibitor that has been approved to treat plaque psoriasis. However, few reports have become available on its efficacy profile in the real-world. Our objective was to study the mid-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the Spanish routine clinical practice setting. This was a retrospective multicenter study that included a total of 91 psoriatic patients on tildrakizumab. The mean Psoriasis Area and Severity Index (PASI) was 9.09 (SD, 5.30). The overall tildrakizumab survival rate was 93.47% for a mean treatment exposure of 30.18 weeks (SD, 16.57). No drug discontinuation was associated with drug tolerability, or adverse reactions. Absolute PASI ≤3 was reached by 91.3% and 96.5% of the patients on weeks 28 and 52, respectively. Response was not impacted by weight, age (>65), metabolic syndrome, presence of arthritis, or previous number of biological therapies used. Based on our own experience tildrakizumab is an effective strategy to treat plaque psoriasis and difficult-to-treat-areas.

Determinant Factors of Disease Severity for Patients With Hidradenitis Suppurativa Evaluated in a Spanish Hospital Over a 5-Year Period.

It is necessary to identify which factors or comorbidities are associated with more severe hidradenitis suppurativa, aiming to identify which patients may benefit more from early systemic treatment or a more aggressive approach. A retrospective study was conducted, including patients diagnosed with HS at the dermatology department of a Spanish hospital over a 5-year period. A total of 322 patients were included. A relationship was found between diagnostic delay, the presence of acne conglobata, pilonidal sinus, cardiovascular risk factors (hypertension, dyslipidemia, and/or diabetes mellitus) and more severe HS. No significant relationship was found between psychiatric comorbidities and the severity of the HS. The presence of perianal or truncal involvement was significantly associated with severe HS. Female sex and the presence of a family history of HS were associated with an earlier onset of the disease.

Upadacitinib effectiveness in moderate-to-severe atopic dermatitis: A real-life multicentre and retrospective study.

This was an observational and retrospective multicentre study conducted on adolescents and adults diagnosed with moderate-to-severe atopic dermatitis (AD) and treated with upadacitinib. Disease severity was measured by Eczema Area and Severity Index (EASI), validated investigator global assessment for AD and pruritus Numerical Rating Scale (NRS) at baseline and Weeks 4, 16, 24 and 52 (when available). Twenty-one patients were included. All patients had previously received topical and systemic corticosteroids. Rapid response to upadacitinib was observed: Mean (SD) EASI score was 19.8 (6.5) at baseline, and 3.1 (4.2), 0.9 (1.4), 0.6 (0.6) and 0.6 (0.6) at the Weeks 4, 16, 24 and 52, respectively. Itch was controlled at Week 4 in all patients (mean [SD] NRS score 7.6 [1.9] baseline, 1.5 [1.3] W4). Severe infections or major adverse cardiovascular events were not reported. We highlight effectiveness and rapid response of upadacitinib in achieving itch control even in long-standing recalcitrant cases.

Congenital and Infantile Hemangiomas: Epidemiological, Clinical, and Treatment Characteristics Based on 3 Years' Experience at a Tertiary Care Hospital - A Retrospective Case Comparison and Review of the Literature. / Características clínico-epidemiológicas y consideraciones terapéuticas de los hemangiomas congénitos e infantiles de un hospital de tercer nivel durante un periodo de 3 años: estudio comparativo y revisión de la literatura.

Distinguishing between congenital and infantile hemangiomas is challenging, but essential for appropriate treatment. The immunohistochemical marker glucose transporter type 1 is helpful, but biopsies are uncommon in this setting. The aim of this retrospective study was to describe and compare epidemiological, clinical, and treatment characteristics of congenital and infantile hemangiomas diagnosed at a tertiary care hospital over 3 years. We studied 107 hemangiomas: 34 congenital hemangiomas (rapidly involuting, partially involuting, and noninvoluting), 70 infantile hemangiomas, and 3 hemangiomas pending classification. Superficial infantile hemangiomas of the head and neck were the most prevalent tumors. Congenital hemangiomas were most often located on the trunk. Studied risk factors were more common in patients with infantile hemangiomas. In this group of patients, treatment response was independent of sex, in vitro fertilization, lesion depth and location, and type of treatment.

Mathematical modeling and quality parameters of Salicornia fruticosa dried by convective drying.

The effect of convective drying at 50, 60 and 70 °C on the drying kinetics and quality parameters of Salicornia fruticosa was investigated. To estimate the equilibrium moisture content a desorption isotherm was performed using five empirical models: Halsey, Caurie, Henderson, Smith and Oswin. The experimental data was also fitted to different drying kinetic models (Logarithmic, Two-Terms, Midilli-Kucuk and Exponential Two-Terms). A numerical simulation using the Finite Volume Method allowed us to describe the evolution of temperature and moisture content distributions during drying. The Henderson model was found to be the most suitable for predicting the equilibrium moisture content of S. fruticosa, with values of X we in the drying process of 1.51; 1.54 and 1.36 g water/g d.m for 50, 60 and 70 °C, respectively. A good agreement was found between the numerical and experimental results of temperature and moisture during Salicornia drying. The Midilli-Kucuk model presented the best fitting to the drying curves. The effects of drying on S. fruticosa were significant in two quality parameters. Antioxidant capacity decreased in ca. 45% and lightness (> L*) significantly increased at a drying temperature of 70 °C, compared to the fresh samples. The optimum drying temperature where drying time and nutrients loss was minimum was 70 °C. These results can be used to estimate the best drying conditions for producing dehydrated Salicornia. The use of halophytes as sustainable crops is promising, and the vision of their commercial production must be evaluated and considered, given water scarcity in many areas of the planet.

Biphasic Computational Fluid Dynamics Modelling of the Mixture in an Agricultural Sprayer Tank.

Agitation inside agricultural sprayer tanks can be studied while using an international standard procedure, based on obtaining internal samples of liquid. However, in practice, this test is not easy to perform. Herein, we propose the explicit study of the mixing procedure with biphasic computer simulations using Computational Fluid Dynamics (CFD). An experimental test was performed on a 3000 L tank of a commercial air-assisted sprayer, with two different agitation system configurations, in order to compare the results of several theoretical physical models of biphasic flows for CFD, both Eulerian and Lagrangian. From the analysis of these theoretical models, we conclude that the Volume of Fluid model is not viable and the Discrete Phase Model produces erroneous results, while the Eulerian and Mixture models can both be useful. However, the results obtained suggest that complex streams generated by real-world agitation systems produce more errors in calculations. Both models can be conducted in the design phase, prior to the implementation of the machine. In addition, the computer simulations allow for researchers to analyse the mixing process in detail, making it possible to evaluate the efficiency of an agitation system according to the time that is required to reach mixture homogeneity.

Overactive bladder symptom bother and health-related quality of life in patients with systemic lupus erythematosus and primary Sjögren syndrome.

OBJECTIVE: The objective of this paper is to assess overactive bladder (OAB) symptom bother (SB) and health-related quality of life (HRQL) among patients with systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS). METHODS: We recruited adult SLE and pSS patients and two groups of age- and sex-matched controls. We applied the OAB questionnaire-short form (OABq-SF) to all participants to assess SB and HRQL and collected clinical information relevant for OAB. We compared the OABq-SF scores for SB and HRQL between patients and controls using univariate and multivariate linear regression analysis. RESULTS: We recruited 95 rheumatic patients (68 SLE, 27 pSS) and 231 controls. Compared to controls SLE patients showed higher OABq-SF SB scores (22.6 ± 20.4 vs 14.7 ± 17.0, p = 0.004) and lower HRQL scores (89.8 ± 15.8 vs 93.8 ± 11.4, p = 0.044). On multivariate analysis SLE was significantly associated with a higher SB score (ß-coefficient 7.13, p = 0.008) and tended to be associated with worse HRQL values (ß-coefficient -3.53, p = 0.055). Patients with pSS had numerically higher mean SB scores (22.8 ± 22.5 vs 16.2 ± 18.0, respectively, p = 0.107) and lower HRQL scores (91.0 ± 10.7 vs 93.2 ± 11.6, respectively, p = 0.369), although these differences were not statistically significant. Diagnosis of pSS was not significantly associated with SB or HRQL scores on univariate or multivariate analysis. CONCLUSIONS: Patients with SLE have significantly worse OAB-SB and poorer HRQL compared to controls. A similar trend was seen for pSS patients, especially for SB. These findings suggest that clinically subtle OAB symptoms may be present in rheumatic patients for whom, later on, bladder pain syndrome may occur.

Preventing the recurrence of depression with a Mediterranean diet supplemented with extra-virgin olive oil. The PREDI-DEP trial: study protocol.

BACKGROUND: The role of dietary patterns in the prevention of unipolar depression has been analyzed in several epidemiological studies. The primary aims of this study are to determine the effectiveness of an extra-olive oil-enriched Mediterranean diet in reducing the recurrence of depression and improving the symptoms of this condition. METHODS: Multicenter, two-arm, parallel-group clinical trial. Arm 1, extra-virgin olive oil Mediterranean diet; Arm 2, control group without nutritional intervention. Dieticians are in charge of the nutritional intervention and regular contact with the participants. Contacts are made through our web platform ( https://predidep.es/participantes/ ) or by phone. Recurrence of depression is assessed by psychiatrists and clinical psychologists through clinical evaluations (semi-structured clinical interviews: Spanish SCID-I). Depressive symptoms are assessed with the Beck Depression Inventory. Information on quality of life, level of physical activity, dietary habits, and blood, urine and stool samples are collected after the subject has agreed to participate in the study and once a year. DISCUSSION: To the best of our knowledge, the PREDI-DEP trial is the first ongoing randomized clinical trial designed to assess the role of the Mediterranean diet in the prevention of recurrent depression. It could be a cost-effective approach to avoid recurrence and improve the quality of life of these patients. TRIAL REGISTRATION: The study has been prospectively registered in the U.S. National Library of Medicine ( https://clinicaltrials.gov ) with NCT number: NCT03081065.

Self-perceived level of competitiveness, tension, and dependency and lifestyles in the 'Seguimiento Universidad de Navarra' cohort study.

OBJECTIVE: The objective of this study is to assess the differences in lifestyles according to levels of self-perceived competitiveness, psychological tension, and dependency in a Mediterranean cohort of university graduates. STUDY DESIGN: Levels of personality traits, food consumption, nutrient intake, eating attitudes, physical activity, sedentary lifestyle, and alcohol and tobacco consumption were assessed through a questionnaire administered at baseline. This was a cross-sectional study in the context of the Seguimiento Universidad de Navarra cohort. Participants are 15,346 Spanish adults. RESULTS: Participants with a high level of self-perceived competitiveness consumed more vegetables and fish but less refined grains; they had higher protein intake and healthier eating attitudes. They were more physically active and less likely to be smokers. Participants with a high level of tension or dependency were less physically active, and participants more dependent also had poorer adherence to the Mediterranean diet. CONCLUSIONS: Self-perceived personality traits, especially the trait of competitiveness, are likely to be associated with healthier dietary patterns, better nutrient profile, better eating attitudes, physical activity, and less exposure to smoking. The use of short questions about self-perceived levels of competitiveness, psychological tension, and dependency can contribute to add additional information when assessing lifestyles and diet in adults.

Application of an Acoustic Doppler Velocimeter to Analyse the Performance of the Hydraulic Agitation System of an Agricultural Sprayer.

An acoustic Doppler velocimeter (ADV) was used to analyse the impact of an agricultural sprayer's agitation system settings on fluid velocities inside the tank. A 3000 L capacity sprayer equipped with a 4-nozzle hydraulic agitation system was used. ADV measurements were carried at 32 points inside the tank under the following settings: circuit pressures of 8, 10, or 12 bar; water level in the tank of 1000, 2000, or 3000 L; 2 or 4 active nozzles. An agitation test with a concentration of 0.4% copper oxychloride was employed to analyse the concentration of active matter as a function of tank fill level and number of active nozzles. All parameters significantly affected the fluid velocity, which increased with increasing pressure, but decreased with increasing water level in the tank and an increased number of active nozzles. Concentration tests showed greater active matter concentrations when higher velocities were recorded by the ADV. The ADV was shown to be a useful tool for the rapid assessment of fluid velocities; in the future, it could be used to validate the design of agitation systems, and to estimate their capacity to ensure an adequate level of active matter concentration in the fluid.