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Detecting the association of genetic variants to the response of biological therapy represents an important advance in developing a personalized therapy. The aim of this work was to study the association of polymorphisms with an optimal response to tildrakizumab in patients with psoriasis in a real-life clinical practice. Ninety patients with plaque psoriasis recruited from-Spanish hospitals receiving tildrakizumab for at least 24 weeks were genotyped for 180 polymorphisms. Optimal response to tildrakizumab was evaluated by absolute PASI ≤1 at 6 and 12 months. Polymorphisms corrected for weight and disease duration with an FDR <0.15 were included in a multiple regression model. Sixty three percent of patients achieved an absolute PASI ≤1 at 6 months, while 71% did so after 12 months. Disease duration (>27 years) and weight (>76 kg) were associated with treatment response; after correcting by these factors, no association (FDR >0.15) was found for any polymorphism and response to tildrakizumab at 6 months. The analysis at 12 months identified the genotype GG for rs610604 (TNFAIP3), CT for rs9373839 (ATG5), and delCTGT/delCTGT for rs72167053 (PDE4D) as risk factors to not achieve an optimal response (PASI ≤1), while CT for rs708567 (IL17RC) was protective, independently of weight and disease duration (FDR <0.15). The final multivariable model at 12 months showed an AUC of 0.90 (95% CI 0.82 to -0.98). We identified a set of polymorphisms that could be helpful to identify psoriatic patients with an optimal response to tildrakizumab at 12 months in real-world practice conditions.
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Anticuerpos Monoclonales Humanizados , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Femenino , Masculino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto , Polimorfismo de Nucleótido Simple , Resultado del Tratamiento , Genotipo , Anciano , Polimorfismo GenéticoRESUMEN
BACKGROUND AND OBJECTIVE: Burnout syndrome is a mental health disorder due to chronic occupational stress. Both burnout and associated comorbidities are prevalent among health care professionals, being medical residents a vulnerable group. Despite this, the scientific medical literature currently available on this issue in dermatology residents is scarce. The aim of this study was to analyze the prevalence of the burnout syndrome, anxiety, and depression in dermatology residents, and the associated risk factors. MATERIAL AND METHOD: This was a cross-sectional trial designed to include dermatology residents from Spain (from December 2022 through June 2023). A self-administered form was sent via online messaging applications, including validated scales to study professional quality of life, burnout syndrome, anxiety, and depression. RESULTS: A total of 48 dermatology residents were included in the study, 50% of whom (24/48) were women, with a mean age of 27 years (1.25). A total of 58.33% (28/48) of the residents had some degree of anxiety, 22.9% (11/48) some degree of depression, and 23.4% a moderate risk of burnout (11/48). Workload was the main risk factor associated with the 3 disorders studied, while managerial support or intrinsic motivation seem to play a protective role. CONCLUSIONS: Burnout syndrome and its comorbidities are both prevalent in dermatology residents in Spain and closely related to each other.
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BACKGROUND: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. OBJECTIVE: To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. MATERIAL & METHODS: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. RESULTS: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. CONCLUSIONS: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future.
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COVID-19 , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Pandemias , COVID-19/epidemiología , Estudios TransversalesRESUMEN
BACKGROUND: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. OBJECTIVE: To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. MATERIAL & METHODS: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. RESULTS: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. CONCLUSIONS: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future.
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COVID-19 , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/patología , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/cirugía , Neoplasias Cutáneas/patología , Pandemias , COVID-19/epidemiología , Estudios TransversalesRESUMEN
BACKGROUND AND OBJECTIVE: Quality of professional life (QPL) is defined as a sense of well-being derived from a balance between the challenges of work and the resources available to deal with them. Impaired QPL can contribute to burnout. The aim of this study was to evaluate QPL in Spanish dermatologists using a validated questionnaire. MATERIAL AND METHODS: We designed a cross-sectional study in which Spanish dermatologists were invited to complete an online questionnaire sent out by messaging applications. The dermatologists were asked to provide sociodemographic information, answer 3 open questions, and complete the 35-item Spanish QPL questionnaire (Spanish abbreviation, CVP-35). RESULTS: We analyzed the information submitted by 106 dermatologists (62 women, 58%) with a mean age of 41 years (95% CI, 43.3-38.8 years). Women and department heads scored significantly higher in the workload domain of the questionnaire (P=.02 and P=.005, respectively). A heavy caseload was mentioned as the main factor contributing to impaired QPL and the main change in the wake of the COVID-19 pandemic. CONCLUSIONS: Female dermatologists reported heavier workloads. Heavy caseloads and more remote work were the main changes identified after the COVID-19 pandemic. Heavy caseloads have a significant impact on the QPL of dermatologists in Spain. Reducing caseloads would improve general job satisfaction and quality of care provision.
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Agotamiento Profesional , COVID-19 , Humanos , Femenino , Adulto , Dermatólogos , Estudios Transversales , Pandemias , COVID-19/epidemiología , Satisfacción en el Trabajo , Encuestas y Cuestionarios , Agotamiento Profesional/epidemiologíaRESUMEN
INTRODUCTION: Neutral argon plasma (NAP) system could meet the requirements to achieve oncological cytoreduction of peritoneal carcinomatosis with miliary lesions, minimizing the associated morbidity. This phase I/II trial aims to establish the desirable dose that is safe and effective in eliminating tumor cells with lower penetration. METHODS: Patients diagnosed with different origins for peritoneal carcinomatosis and miliary implants were selected for the study. The safe and potentially effective dose (desirability) of NAP was evaluated according to three factors: distance (mm), application time (s) and power (%), to evaluate the response variables such as the presence of tumor cells (Y/N) and the depth of penetration. RESULTS: Ten patients and 120 samples were evaluated and treated with NAP. There was no vascular or organ injury intraoperative using a pre-established dose of 100% (coagulation mode) at a distance of 2-3 cm. The distance was found to be correlated with the presence of the tumor cells in ex-vivo analysis, with an OR of 15.4 (4.0-111.4). The time and energy used were protective factors to eliminate tumor cells with an OR of 0.4 (0.1-0.9) and 0.8 (0.8-0.9), respectively. The safest and most effective desirability results were as follows i) energy 80% during 2-4 s with a distance of 2 cm (0.89), and ii) energy 100% during 2-4 s with a distance of 3 cm (0.90). CONCLUSIONS: The use of NAP during a CRS and HIPEC is safe and effective for eradicating tumor cells on the peritoneal surface at suggested doses of energy, distance and duration. TRIAL IDENTIFICATION: ClinicalTrials.gov Identifier: NCT04904042.
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Hipertermia Inducida , Neoplasias Peritoneales , Gases em Plasma , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Neoplasias Peritoneales/cirugía , Tasa de SupervivenciaRESUMEN
BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare malignant disease. Adding of the Ki67 proliferation index to the PSOGI PMP classification provided two different subcategories of the extensive HG-PMP group (HG-PMP ≤15% and HG-PMP >15%) with different survival in a previous unicentric study. This study aims to carry out an external and multicentre validation of this new proposed classification. METHOD: It was a prospective analysis of samples from a historical and international cohort of patients. A representative area with higher cellular density was used to determine the Ki67%. The Ki67 proliferation index (%) was determined in all the HG-PMP patients. A Cox proportional hazard models and multivariable COX models were used. The Kaplan-Meier method and the two-tailed log-rank test were used to analyse the effect of different PSOGI-Ki67 categories on OS and DFS. Its predictive accuracy was analysed using Harrel's C-index and the ROC curve. The calibration was performed using the calibration plots matching. RESULTS: After exclusions, 349 patients were available for analysis. The 5-years OS were 86% for LG-PMP, 59% for HG-PMP≤15, 38% for HG-PMP>15 and 42% for SRC-PMP (p = 0.0001). The 5-years DFS were 49% for LG-PMP, 35% for HG-PMP≤15, 16% for HG-PMP>15 and 18% SRC-PMP (p = 0.0001). The discrimination capability of PSOGI-Ki67 was validated. CONCLUSION: the PSOGI-Ki67 classification discriminates and predicts the OS and DFS in patients with PMP dividing the HG-PMP category into two well-defined sub-categories. The Ki67 proliferation index should be incorporated routinely in the pathology report for these patients.
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Neoplasias Peritoneales , Seudomixoma Peritoneal , Humanos , Seudomixoma Peritoneal/patología , Antígeno Ki-67 , Neoplasias Peritoneales/patología , Pronóstico , Modelos de Riesgos Proporcionales , Estudios RetrospectivosRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global pandemic that has spread all over the word. To avoid the virus transmission, healthcare workers must wear adequate personal protective equipment (PPE). PPE is associated with several side events, including skin reactions. The objective of this study was to summarize the prevalence, type and risk factors for cutaneous adverse events related to PPE and prevention measures to avoid them. A systematic review and meta-analysis was conducted using MEDLINE, Scopus and EMBASE databases from conception to 21 January 2021. All types of epidemiological studies regarding skin adverse events related to PPE were included. The literature search identified 1007 references, 35 of them met the eligible criteria and were included for analysis, representing 31 453 participants. The media of skin side events related to PPE was 75.13%. The rate of cutaneous adverse events related to mask was 57.71%, and those associated with gloves and hand hygiene products was 49.16%. Most common skin adverse events were contact dermatitis, acne and itching. The most damaged anatomical regions were the nasal bridge, the cheeks and the hands. The duration of PPE wearing was the most common risk factor. Frequent handwashing, gloves and masks were the agents most frequently related to skin reactions. N95 respirators were the most harmful mask type for the skin. Hydrocolloid use prevented from developing skin adverse events related to masks. In conclusion, the rate of cutaneous adverse events related to PPE use is high. A longer duration of PPE wearing was the most common risk factor. Using hydrocolloid could prevent from skin injuries related to mask use.
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COVID-19 , Equipo de Protección Personal , Personal de Salud , Humanos , Pandemias , SARS-CoV-2RESUMEN
The aim was to produce PEG-coated nanoparticles (NP-PEG), with mucus-permeating properties, for oral drug delivery purposes by using simple procedures and regulatory-approved compounds in order to facilitate a potential clinical development. For this purpose, zein nanoparticles were prepared by desolvation and, then, coated by incubation with PEG 35,000. The resulting nanocarriers displayed a mean size of about 200 nm and a negative zeta potential. The presence of PEG on the surface of nanoparticles was evidenced by electron microscopy and confirmed by FTIR analysis. Likely, the hydrophobic surface of zein nanoparticles (NP) was significantly reduce by their coating with PEG. This increase of the hydrophilicity of PEG-coated nanoparticles was associated with an important increase of their mobility in pig intestinal mucus. In laboratory animals, NP-PEG (fluorescently labelled with Lumogen® Red 305) displayed a different behavior when compared with bare nanoparticles. After oral administration, NP appeared to be trapped in the mucus mesh, whereas NP-PEG were capable of crossing the protective mucus layer and reach the epithelium. Finally, PEG-coated zein nanoparticles, prepared by a simple and reproducible method without employing reactive reagents, may be adequate carriers for promoting the oral bioavailability of biomacromolecules and other biologically active compounds with low permeability properties.
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Nanopartículas , Zeína , Administración Oral , Animales , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Moco , Tamaño de la Partícula , PorcinosAsunto(s)
Dermatología , Internado y Residencia , Dermatología/educación , España , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To optimize radiolabeling with 99mTc and 67Ga of albumin nanoparticles coated with 4 differents synthetic polymers and to evaluate their stability in vivo and in vitro, as well as their biodistribution in vivo after intravenous administration. MATERIAL AND METHODS: The nanoparticles were prepared using albumin and NOTA-modified albumin by the desolvation method and coated with 4 different polymers; HPMC, GMN2, GPM2 and GTM2. They were purified, lyophilized and characterized. Radiolabelling with 99mTc was perfomed with 74 MBq of 99mTc sodium pertechnetate, previously reduced with and acid solution of tin chloride at different concentrations (0.003, 0.005, 0.007, 0.01, 0.05 and 0.1mg/ml) and at different times (5, 10, 15, 30 and 60minutes) and temperatures (room temperature, 40°C and 60°C). Radiolabelling with 67Ga was perfomed by incubation of the nanoparticles with 37 MBq of 67Gallium chloride (obtained from commercial gallium-67 citrate) at different times (10 and 30minutes) and temperatures (room temperature, 30°C and 60°C), and posterior purification with microconcentrators. The radiochemical purity was evaluated by TLC. Stability studies of radiolabeled nanoparticles in physiological serum and blood plasma were perfomed. Biodistribution studies of nanoparticles coated with GPM2 polymer were carried out in Wistar rats after intravenous administration of the nanoparticles. Control animals were carried out with 99mTc sodium pertechnetate and 67Ga chloride. To do so, the animals were killed and activity in organs was measured in a gamma counter. RESULTS: 99mTc labeling was carried out optimally with a tin concentration of 0.007mg/ ml for the GPM2 nanoparticles and 0.005mg / ml for the rest of the formulations, with a radiolabelling time of 10minutes at room temperature. In the case of 67Ga the label was optimized at 30° C temperature and 30minutes of incubation. In both cases the radiochemical purity obtained was greater than 97%. The nanoparticles showed high stability in vitro after 48hours of labeling (70% nanoparticles labeled with 99mTc and 90% those labeled with 67Ga). Biodistribution studies of nanoparticles 99mTc -GPM2 and 67Ga -NOTA-GPM2 showed a high accumulation of activity in the liver at 2 and 24hours after intravenous administration. CONCLUSION: The labeling procedure with 99mTc and 67Ga of albumin and albumin modified with NOTA nanoparticles allows obtaining nanoparticles with high labeling yields and adequate in vitro stability, allowing their use for in vivo studies.
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Radioisótopos de Galio/farmacocinética , Galio/farmacocinética , Marcaje Isotópico/métodos , Nanopartículas/administración & dosificación , Poliaminas/química , Radiofármacos/farmacocinética , Albúmina Sérica Humana/farmacocinética , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , Tecnecio/farmacocinética , Tiamina/química , Animales , Cromatografía en Capa Delgada , Estabilidad de Medicamentos , Femenino , Galio/administración & dosificación , Galio/análisis , Radioisótopos de Galio/administración & dosificación , Radioisótopos de Galio/análisis , Compuestos Heterocíclicos con 1 Anillo , Derivados de la Hipromelosa , Inyecciones Intravenosas , Nanopartículas/análisis , Polietilenglicoles , Radiofármacos/administración & dosificación , Radiofármacos/análisis , Ratas , Ratas Wistar , Albúmina Sérica Humana/administración & dosificación , Albúmina Sérica Humana/análisis , Tecnecio/administración & dosificación , Tecnecio/análisis , Temperatura , Compuestos de Estaño , Distribución TisularRESUMEN
BACKGROUND: There is not an ideal biomaterial for tissue-engineered skin substitutes (TESSs), and most of the studies or existing therapies use xenogeneic origin natural biomaterials or biosynthetic scaffolds. OBJECTIVE: To analyse clinical, histological integration and homeostasis parameters of a human TESS manufactured with fibrin-hyaluronic acid biomaterial (HA-Skin), grafted in immunodeficient mice for 8 weeks, and compared with the gold standard treatment (Autograft), a human TESS manufactured with fibrin-agarose biomaterial (AG-Skin) and secondary wound healing dressings. METHODS: Human TESSs and autografts were implanted into BALB/c mice after surgical excision. Secondary wound healing approach was achieved with biosynthetic collagen wound dressing (Biobrane® ) and fibrin-hyaluronic acid or fibrin-agarose biomaterial without cells (Total N = 44). Clinical integration and homeostasis parameters were evaluated every two weeks for two months. Histological and immunohistochemical analyses were performed four and eight weeks after grafting. RESULTS: HA-Skin, AG-Skin and Autograft groups showed a proper clinical integration and epithelization eight weeks later. Scar evaluation revealed better results for Autograft and HA-Skin. Homeostasis analysis indicated similar values of transepidermal water loss and elasticity between HA-Skin (6.42 ± 0.75 g/h/m2 , 0.42 ± 0.08 AU), Autograft (6.91 ± 1.28 g/h/m2 , 0.40 ± 0.08 AU) and healthy mouse skin (6.40 ± 0.43 g/h/m2 , 0.35 ± 0.03 AU). Histological results showed that human TESSs and autografts presented better skin structuration and higher expression of cytokeratins. CONCLUSIONS: This study suggests that human TESS based on fibrin-hyaluronic acid biomaterial could be suitable for clinical application in the treatment of several dermatological pathologies (wound healing).
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Piel Artificial , Animales , Vendajes , Humanos , Ácido Hialurónico , Ratones , Ratones Endogámicos BALB C , Cicatrización de HeridasRESUMEN
Arabinoxylans (AX) microspheres with different insulin/AX mass ratio were prepared by formation of phenoxy radical issued from the ferulic acid by enzymatic oxidation (entrapped in situ of insulin). Phenolic acid content and FT-IR spectrum of unloaded and insulin-loaded AX microspheres revealed that the phenoxy radical issued from the ferulic acid by enzymatic oxidation did not interact covalently with insulin. The microspheres showed a spherical shape, smooth surface and an average diameter of particles of 320⯵m. In vitro control release found that AX microspheres minimized the insulin loss in the upper GI tract, retaining high percentage (~75%) of insulin in its matrix. The stability of the secondary structure of insulin was studied by dichroism circular (CD). The CD spectra of insulin released from AX microspheres did not change according to the insulin/AX mass ratio of the microsphere. Significant hypoglycemic effects with improved insulin-relative bioavailability tested on an in vivo murine model revealed the efficacy of these enzymatically cross-linked arabinoxylans microspheres as a new oral insulin carrier.
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Reactivos de Enlaces Cruzados/química , Sistemas de Liberación de Medicamentos , Insulina/administración & dosificación , Lacasa/metabolismo , Microesferas , Xilanos/química , Administración Oral , Animales , Glucemia/metabolismo , Liberación de Fármacos , Humanos , Masculino , Ratas Wistar , Reología , Espectroscopía Infrarroja por Transformada de Fourier , Distribución TisularRESUMEN
Chromatin immunoprecipitation (ChIP) and high throughput sequencing (ChIP-seq) have been used to assess histone methylation (epigenetic modification) dynamics within the internal organs of zebrafish after spring viremia of carp virus (SVCV) infection. Our results show H3K4me3 up-methylation in gene promoters associated with innate immune response during the first 5 days after SVCV infection. Gene Ontology (GO) enrichment analysis confirmed up-methylation in 218 genes in the "immune system process" category. In particular, the promoters of interferon (ifn), interferon stimulated genes (isg), Toll-like receptors (tlr) and c-reactive protein (crp) multi gene sets were marked with the permissive H3K4 methylation. Higher histone 3 methylation was associated with higher transcription levels of the corresponding genes. Therefore, the evidence presented here suggests that transcriptional regulation at the promoter level of key immune genes of the interferon signaling pathway and c-reactive proteins genes can be modulated by epigenetic modification of histones. This study emphasizes the importance of epigenetic control in the response of zebrafish to SVCV infection.