RISalud-ANDALUCÍA
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Optical Behavior of Human Skin Substitutes: Absorbance in the 200-400 nm UV Range
No full textThe most recent generation of bioengineered human skin allows for the efficient treatment of patients with severe skin defects. Despite UV sunlight can seriously affect human skin, the optical behavior in the UV range of skin models is still unexplored. In the present study, absorbance and transmittance of the UGRSKIN bioartificial skin substitute generated with human skin cells combined with fibrin-agarose biomaterials were evaluated for: UV-C (200-280 nm), -B (280-315 nm), and -A (315-400 nm) spectral range after 7, 14, 21 and 28 days of ex vivo development. The epidermis of the bioartificial skin substitute was able to mature and differentiate in a time-dependent manner, expressing relevant molecules able to absorb most of the incoming UV radiation. Absorbance spectral behavior of the skin substitutes showed similar patterns to control native skin (VAF > 99.4%), with values 0.85-0.90 times lower than control values at 7 and 14- days and 1.05-1.10 times the control values at 21- and 28-days. UV absorbance increased, and UV transmission decreased with culture time, and comparable results to the control were found at 21 and 28 days. These findings support the use of samples corresponding to 21 or 28 days of development for clinical purposes due to their higher histological similarities with native skin, but also because of their absorbance of UV radiation
In Vitro Activity of Cefepime-Taniborbactam against Carbapenemase-Producing Enterobacterales and Pseudomonas aeruginosa Isolates Recovered in Spain.
No full textNovel β-lactam-β-lactamase inhibitor combinations currently approved for clinical use are poorly active against metallo-β-lactamase (MBL)-producing strains. We evaluated the in vitro activity of cefepime-taniborbactam (FTB [formerly cefepime-VNRX-5133]) and comparator agents against carbapenemase-producing Enterobacterales (n = 247) and carbapenem-resistant Pseudomonas species (n = 170) clinical isolates prospectively collected from different clinical origins in patients admitted to 8 Spanish hospitals. FTB was the most active agent in both Enterobacterales (97.6% MICFTB, ≤8/4 mg/L) and Pseudomonas (67.1% MICFTB, ≤8/4 mg/L) populations. The MICFTB was >8 mg/L in 6/247 (2.4%) Enterobacterales isolates (3 KPC-producing Klebsiella pneumoniae isolates, 1 VIM-producing Enterobacter cloacae isolate, 1 IMP-producing E. cloacae isolate, and 1 NDM-producing Escherichia coli isolate) and in 56/170 (32.9%) Pseudomonas isolates, 19 of them carbapenemase producers (15 producers of VIM, 2 of GES, 1 of GES+VIM, and 1 of GES+KPC). Against the Enterobacterales isolates with meropenem MICs of >2 mg/L (138/247), FTB was the most active agent against both serine-β-lactamases (107/138) and MBL producers (31/138) (97.2 and 93.5% MICFTB, ≤8/4 mg/L, respectively), whereas the activity of comparators was reduced, particularly against the MBL producers (ceftazidime-avibactam, 94.4 and 12.9%, meropenem-vaborbactam, 85.0 and 64.5%, imipenem-relebactam, 76.6 and 9.7%, ceftolozane-tazobactam, 1.9 and 0%, and piperacillin-tazobactam, 0 and 0%, respectively). Among the meropenem-resistant Pseudomonas isolates (163/170; MIC, >2 mg/L), the activities of FTB against serine-β-lactamase (35/163) and MBL (43/163) producers were 88.6 and 65.1%, respectively, whereas the susceptibilities of comparators were as follows: ceftazidime-avibactam, 88.5 and 16.0%, meropenem-vaborbactam, 8.5 and 7.0%, imipenem-relebactam, 2.9 and 2.3%, ceftolozane-tazobactam, 0 and 2.3%, and piperacillin-tazobactam, 0 and 0%, respectively. Microbiological results suggest FTB as a potential therapeutic option in patients infected with carbapenemase-producing Enterobacterales and carbapenem-resistant Pseudomonas isolates, including MBL producers.This project was sponsored by Venatorx Pharmaceuticals and has been funded in wholeor in part with federal funds from the Department of Health and Human Services, Office ofthe Assistant Secretary for Preparedness and Response, Biomedical Advanced Research andDevelopment Authority, under contract no. HHSO100201900007C. This study was alsosupported by Plan Nacional de I1D 1 i 2013–2016 and Instituto de Salud Carlos III,Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio deEconomía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases(RD16/0016/0001, RD16/0016/0004, RD16/0016/0006, RD16/0016/0007, RD16/0016/0008,RD16/0016/0010, and REIPI RD16/0016/0011), cofinanced by the European DevelopmentRegional Fund “A Way to Achieve Europe” (ERDF), operative program Intelligent Growth2014–2020 and CIBER en Enfermedades Infecciosas (CIBERINF) (CB21/13/00084).S
Aripiprazole and Risperidone Present Comparable Long-Term Metabolic Profiles: Data From a Pragmatic Randomized Controlled Trial in Drug-Naïve First-Episode Psychosis.
No full textAripiprazole and risperidone are 2 of the most used second-generation antipsychotics (SGAs) worldwide. Previous evidence shows a similar effect of these SGAs on weight and metabolic changes in the short term. However, a longer period is necessary for a better assessment of the SGA´s metabolic profile. We aimed to compare the long-term (1-year) metabolic profile of these 2 antipsychotics on a sample of drug-naïve first episode-psychosis (FEP) patients. A total 188 drug-naïve patients, suffering from a first episode of non-affective psychosis (FEP), were randomly assigned to treatment with either aripiprazole or risperidone. Weight and glycemic/lipid parameters were recorded at baseline and after 1-year follow-up. We observed significant weight increments in both groups (9.2 kg for aripiprazole and 10.5 kg for risperidone) after 1 year of treatment. Despite this, weight and body mass index changes did not significantly differ between treatment groups (P > .05). Similarly, both treatment groups presented similar metabolic clinical impact with a comparable increase in the proportion of participants meeting criteria for metabolic disorders such as obesity or hypercholesterolemia, but not for metabolic syndrome (Δ9.2% vs Δ4.3%) or hypertriglyceridemia (Δ21.9% vs Δ8.0%), where aripiprazole showed worse outcomes than risperidone. This study shows that aripiprazole and risperidone share a similar long-term metabolic profile. After 1 year of antipsychotic treatment, drug-naïve FEP patients in both treatment groups presented a significant increase in weight and metabolic changes, leading to a greater prevalence of metabolic disorders.S
European consensus-based interdisciplinary guideline for melanoma. Part 2: Treatment - Update 2022.
No full textA unique collaboration of multidisciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO), and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cutaneous melanoma diagnosis and treatment, based on the systematic literature reviews and the experts' experience. Cutaneous melanomas are excised with one to 2-cm safety margins. Sentinel lymph node dissection shall be performed as a staging procedure in patients with tumor thickness ≥1.0 mm or ≥0.8 mm with additional histological risk factors, although there is as yet no clear survival benefit for this approach. Therapeutic decisions in stage III/IV patients should be primarily made by an interdisciplinary oncology team ("tumor board"). Adjuvant therapies can be proposed in stage III/completely resected stage IV patients and are primarily anti-PD-1, independent of mutational status, or alternatively dabrafenib plus trametinib for BRAF mutant patients. In distant metastases (stage IV), either resected or not, systemic treatment is always indicated. For first-line treatment particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies shall be considered. In stage IV melanoma with a BRAF-V600 E/K mutation, first-line therapy with BRAF/MEK inhibitors can be offered as an alternative to immunotherapy. In patients with primary resistance to immunotherapy and harboring a BRAF-V600 E/K mutation, this therapy shall be offered as second-line therapy. Systemic therapy in stage III/IV melanoma is a rapidly changing landscape, and it is likely that these recommendations may change in the near future.S
Progress and Hurdles of Therapeutic Nanosystems against Cancer.
No full textNanomedicine against cancer, including diagnosis, prevention and treatment, has increased expectations for the solution of many biomedical challenges in the fight against this disease. In recent decades, an exhaustive design of nanosystems with high specificity, sensitivity and selectivity has been achieved due to a rigorous control over their physicochemical properties and an understanding of the nano-bio interface. However, despite the considerable progress that has been reached in this field, there are still different hurdles that limit the clinical application of these nanosystems, which, along with their possible solutions, have been reviewed in this work. Specifically, physiological processes as biological barriers and protein corona formation related to the administration routes, designing strategies to overcome these obstacles, promising new multifunctional nanotherapeutics, and recent clinical trials are presented in this review
A brownish erythematous patch in the nipple-areola complex.
No full textAn 85-year-old woman presented with a 9-month history of pruritus in the left breast and unremarkable medical history. On examination, a brownish erythematous patch was observed in the nipple-areola complex (Figure 1). Skin-punch biopsy revealed single cells and small clusters of neoplastic cells throughout the epidermis and granular layer, with abundant pale cytoplasm, intraglandular extension, and chronic infl ammation in the papillary dermis (Figure 2), resulting in the diagnosis of Paget disease of the breast.N
Are infections in children with juvenile idiopathic arthritis more frequent than in healthy children? A prospective multicenter observational study.
No full textChildren with juvenile idiopathic arthritis (JIA) might be at a higher risk of infection. Our objectives are to describe and compare infection rates in patients with JIA vs. healthy patients. A prospective, multicenter observational study was performed in Spain from January 2017 to June 2019. Patients with JIA from 7 participating hospitals and children without JIA (siblings of patients with JIA, and non-JIA children from primary health centers) were followed up with quarterly questionnaires to record infection episodes. Tuberculosis, herpes zoster, and infections requiring hospital admission were considered severe infections. Rates of infection (episodes/patient/year) were compared using a generalized estimating equations model. A total of 371 children (181 with and 190 without JIA) were included. The median age was 8.8 years (IQR 5.5-11.3); 75% of the patients with JIA received immunosuppressive treatment (24% methotrexate, 22% biologic, 26% both). A total of 667 infections were recorded; 15 (2.2%) were considered severe. The infection rate was 1.31 (95%CI 1.1-1.5) in JIA and 1.12 (95%CI 0.9-1.3) in non-JIA participants (p = 0.19). Age We found no differences in the infection rate or infection severity between patients with and without JIA. Most infections were mild. An age younger than 4 years increased the infection risk in both groups. Higher disease activity was associated with a higher infection rate.S
Real-Life Early Anthropometric, Lipid and Liver Changes after Direct-Acting Antiviral Therapy in PLWHIV with HCV Co-Infection.
No full textTreatment with interferon-free direct-acting antivirals (DAA) has become the gold standard in chronic hepatitis C virus (HCV) infection. Nevertheless, little research about the metabolic impact of achieving sustained virological response (SVR) is available in HCV/HIV co-infected patients. This research aimed to evaluate early anthropometric, lipid and liver parameters changes after achieving SVR 12 weeks after treatment (SVR12). A real-life retrospective descriptive before-after study assessed 128 DAA treatment episodes from 2015 to 2019 in HCV/HIV co-infected patients. Anthropometric parameters (weight, body mass index), lipid profile, genotype (GT) and viral load, liver data (basics laboratory necroinflammatory parameters and transient elastography (TE)) were collected before treatment with DAA (baseline), and when SVR12 was achieved. Significant increases (
COVID-19 vaccination in patients receiving allergen immunotherapy (AIT) or biologicals-EAACI recommendations.
No full textImmune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen-specific manner via allergen immunotherapy (AIT) or in an endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)-5 and IL-4/IL-13 or non-type 2 response: anti-cytokine antibodies and B-cell depletion via anti-CD20. Coronavirus disease 2019 (COVID-19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.S
Immersive Virtual Reality and Vestibular Rehabilitation in Multiple Sclerosis: Case Report.
No full textDizziness and imbalance are common and disabling symptoms in patients with multiple sclerosis (MS) and are caused by a central, peripheral, or mixed vestibulopathy. Central vestibular disorder is the most frequently reported vestibular problem in the MS population due to demyelination. Vestibular rehabilitation ameliorates these symptoms and their repercussions and improves quality of life. Immersive virtual reality (VRi) is an emerging tool in this field; however, no previous research has been performed studying its effects in MS. The aim of this study was to apply a VRi vestibular training protocol to a patient with MS and assess the effects induced by the experimental intervention. This case study included a 54-year-old woman with relapsing-remitting MS. We developed a standardized VRi exercise protocol for vestibular rehabilitation based on the gold-standard Cawthorne-Cooksey vestibular training protocol. The 20-session intervention was made up of 10 initial sessions and 10 advanced sessions. Each 50-minute session was performed two to three times per week for 7 weeks. Four evaluations were carried out over the study period: at baseline (T0), between initial and advances phases (T1), postintervention (T2), and 1 month after the experimental procedure (T3). The research outcomes were dizziness, balance, gait, impact of fatigue, quality of life, repercussions in muscular tone, and usability of the head-mounted display device. After implementing the VRi vestibular protocol, improvements were seen in the following patient parameters: Dizziness Handicap Inventory score (62 points at T0; 4 points at T2); Berg Balance Scale score (47 points at T0; 54 points at T2); instrumented Timed Up and Go time (8.35 seconds at T0; 5.57 seconds at T2); muscular tone of the erector spinae, rectus femoris, and soleus; Modified Fatigue Impact Scale score (61 points at T0; 37 points at T2); and Multiple Sclerosis Quality of Life-54 values (67.16% in the physical health area at T2; 33.56% in the mental health area at T2). The patient rated the usability of the system as 90%, based on the System Usability Scale, and gave the system a grade of A. Although further research is needed, this study provided initial evidence that the first VRi vestibular protocol for the MS population can improve dizziness, balance, gait, impact of fatigue, quality of life, and muscular tone through an exergame intervention. This study may help establish a standardized VRi protocol for vestibular rehabilitation