Análisis de la Ley 3/2019, de 18 de febrero, de la Generalitat de Servicios Sociales Inclusivos de la Comunidad Valenciana. Una perspectiva de su impacto de género.

Treball final de Màster Universitari en Igualtat i Gènere en l'Àmbit Públic i Privat (Pla de 2013). Codi: SRM042. Curs acadèmic 2019-2020Analysis of Law 3/2019, of February 18, of the Generalitat, on Inclusive Social Services of the Valencian Community. A perspective of its gender impact

Role of age and sex in the diagnosis of early-stage malignant melanoma: A cross-sectional study

Age and sex have been identified as predictors of outcome in malignant melanoma (MM). The aim of this multicentre, cross-sectional study was to analyse the role of age and sex as explanatory variables for the diagnosis of thin MM. A total of 2,430 patients with MM were recruited. Cases of in situ (Tis) and T1 MM were more frequent than T2–T4 MM (56.26% vs. 43.74%). Breslow thickness increased throughout decades of life (analysis of variance (ANOVA) p < 0.001), with a weak correlation between Breslow thickness and patient's age (r = 0.202, p < 0.001). Breslow thickness was significantly less in women (1.79 vs. 2.38 mm, p = 0.0001). Binary logistic regression showed a significant (p < 0.001) odds ratio for age 0–29 years (1.18), and 30–59 years (1.16), and for women (1.09). Age and sex explained 3.64% of the variation observed in Tis–T1 frequency (R2 = 0.0364). Age and sex appear to explain a low percentage of the variation in the early detection of MM

Surgery for cutaneous squamous cell carcinoma and its limits in advanced disease

Surgery remains the first-line therapeutic option for most patients with cutaneous squamous cell carcinoma (cSCC). However, in the current therapeutic landscape, surgery must attempt to the complete tumor resection (R0 resection) with the lowest risk of surgical complications. This double aim is usually accomplished through standard excision with clinical margins in patients with low-risk tumors or by some of the micrographically controlled surgery procedures for patients with tumors at high-risk of local recurrence and metastasis. Surgery is also a first-line treatment for nodal metastases of cSCC as well as an option to consider in patients who develop recurrences while receiving immunotherapy, or as a palliation procedure in patients with advanced tumors. Neoadjuvant immunotherapy, that is the use of a medical treatment before surgery, is under investigation in patients with cSCC. The decision-making process and guidelines recommendations regarding cSCC surgery are reviewed in this manuscript

Sentinel lymph node biopsy vs. Observation in thin melanoma: A multicenter propensity score matching study

The therapeutic value of sentinel lymph node biopsy (SLNB) in thin melanoma remains controversial. The aim of this study is to determine the role of SLNB in the survival of thin melanomas (≤1 mm). A multicenter retrospective observational study was designed. A propensity score matching was performed to compare patients who underwent SLNB vs. observation. A multivariate Cox regression was used. A total of 1438 patients were matched by propensity score. There were no significant differences in melanoma-specific survival (MSS) between the SLNB and observation groups. Predictors of MSS in the multivariate model were age, tumor thickness, ulceration, and interferon treatment. Results were similar for disease-free survival and overall survival. The 5- and 10-year MSS rates for SLN-negative and -positive patients were 98.5% vs. 77.3% (p < 0.001) and 97.3% vs. 68.7% (p < 0.001), respectively. SLNB does not improve MSS in patients with thin melanoma. It also had no impact on DSF or OS. However, a considerable difference in MSS, DFS, and OS between SLN-positive and -negative patients exists, confirming its value as a prognostic procedure and therefore we recommend discussing the option of SLNB with patients

Alginate-Agarose Hydrogels Improve the In Vitro Differentiation of Human Dental Pulp Stem Cells in Chondrocytes. A Histological Study

[EN] Matrix-assisted autologous chondrocyte implantation (MACI) has shown promising results for cartilage repair, combining cultured chondrocytes and hydrogels, including alginate. The ability of chondrocytes for MACI is limited by different factors including donor site morbidity, dedifferentiation, limited lifespan or poor proliferation in vitro. Mesenchymal stem cells could represent an alternative for cartilage regeneration. In this study, we propose a MACI scaffold consisting of a mixed alginate-agarose hydrogel in combination with human dental pulp stem cells (hDPSCs), suitable for cartilage regeneration. Scaffolds were characterized according to their rheological properties, and their histomorphometric and molecular biology results. Agarose significantly improved the biomechanical behavior of the alginate scaffolds. Large scaffolds were manufactured, and a homogeneous distribution of cells was observed within them. Although primary chondrocytes showed a greater capacity for chondrogenic differentiation, hDPSCs cultured in the scaffolds formed large aggregates of cells, acquired a rounded morphology and expressed high amounts of type II collagen and aggrecan. Cells cultured in the scaffolds expressed not only chondral matrix-related genes, but also remodeling proteins and chondrocyte differentiation factors. The degree of differentiation of cells was proportional to the number and size of the cell aggregates that were formed in the hydrogels.This work was funded by the Ministry of Economy and Competitiveness of the Spanish Government (PID2019-106099RB-C42, MM) and by the Generalitat Valenciana, Spain (PROMETEO/2020/069, CC). CIBER-BBN and CIBER-ER are financed by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and the Instituto de Salud Carlos III, with assistance of the European Regional Development Fund.Oliver-Ferrándiz, M.; Milián, L.; Sancho-Tello, M.; Martín De Llano, JJ.; Gisbert-Roca, F.; Martínez-Ramos, C.; Carda, C.... (2021). Alginate-Agarose Hydrogels Improve the In Vitro Differentiation of Human Dental Pulp Stem Cells in Chondrocytes. A Histological Study. Biomedicines. 9(7):1-22. https://doi.org/10.3390/biomedicines9070834S1229

A Comparative Study of Cell Culture Conditions during Conversion from Primed to Naive Human Pluripotent Stem Cells

The successful reprogramming of human somatic cells into induced pluripotent stem cells (hiPSCs) represented a turning point in the stem cell research field, owing to their ability to differentiate into any cell type with fewer ethical issues than human embryonic stem cells (hESCs). In mice, PSCs are thought to exist in a naive state, the cell culture equivalent of the immature pre-implantation embryo, whereas in humans, PSCs are in a primed state, which is a more committed pluripotent state than a naive state. Recent studies have focused on capturing a similar cell stage in human cells. Given their earlier developmental stage and therefore lack of cell-of-origin epigenetic memory, these cells would be better candidates for further re-differentiation, use in disease modeling, regenerative medicine and drug discovery. In this study, we used primed hiPSCs and hESCs to evaluate the successful establishment and maintenance of a naive cell stage using three different naive-conversion media, both in the feeder and feeder-free cells conditions. In addition, we compared the directed differentiation capacity of primed and naive cells into the three germ layers and characterized these different cell stages with commonly used pluripotent and lineage-specific markers. Our results show that, in general, naive culture NHSM medium (in both feeder and feeder-free systems) confers greater hiPSCs and hESCs viability and the highest naive pluripotency markers expression. This medium also allows better cell differentiation cells toward endoderm and mesoderm.This work was supported by the Health Department of the Basque Government (Grant 2019111068, 2019/4703, 2020111058, 2020333032, 2021333057 and 2021333012), Merck-Salud Founda- tion (FSALUD17/004), Economic Development and Infrastructures Department of the Basque Govern- ment (KK-2020/00068), EITB Maratoia (BIO21/COV/030), Project “PI18/01299” and “PI21/01187”, funded by Instituto de Salud Carlos III and co-funded by European Union (ERDF) “A way to make Europe”, “ICI21/00095” funded by Instituto de Salud Carlos III and co-funded by European Union (NextGenerationEU), “Plan de Recuperación Transformación y Resiliencia” Investigación Clínica Independiente 2021–Acción Estratégica Salud 2017–2020, RICORS: (RD21/00017/0024) Red Española de Terapias Avanzadas TERAV ISCIII. Funded by Instituto de Salud Carlos III (ISCIII) and co-funded by European Union (NextGenerationEU) “Plan de Recuperación Transformación y Resiliencia” Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) 2021–Acción Estratégica Salud 2017–2020. L.H. was supported by the Jesus Gangoiti Barrera Foundation and the Asociación Española contra el Cáncer (AECC) AECC16/501 and the Fundación Mutua Madrileña AP176182020. M.M-I was supported by Jesus Gangoiti Barrera Foundation. I.R was supported by Margarita Salas Grant “MARSA21/60” and the Jesus Gangoiti Barrera Foundation. M.I-F. was supported by Inocente Inocente Foundation FII18/003. J.R.P. has grant “RYC-2013-13450” funded by MCIN/AEI/10.13039/501100011033, by the European Social Fund “ESF investing in your future”

Role of Isolated Limb Perfusion in the Era of Targeted Therapies and Immunotherapy in Melanoma. A Systematic Review of The Literature

Background. Isolated limb perfusion (ILP) is a locoregional procedure indicated by the unresectable melanoma of the limbs. Its complexity and highly demanding multidisciplinary approach means that it is a technique only implemented in a few referral centers around the globe. This report aims to examine its potential role in the era of targeted therapies and immunotherapy by conducting a systematic review of the literature on ILP. Methods. PubMed, Embase and Cochrane Library were searched. The eligibility criteria included publications from 2000–2020 providing valid data o effectiveness, survival or toxicity. Studies in which the perfusion methodology was not clearly described, letters to the editor, non-systematic reviews and studies that applied outdated clinical guidelines were excluded. To rule out studies of a low methodological quality and assess the risk of bias, the following aspects were also required: a detailed description of the applied ILP regimen, the clinical context, follow-up periods, analyzed clinical endpoints, and the number of analyzed ILPs. The disagreements were resolved by consensus. The results are presented in tables and figures. Results. Twenty-seven studies including 2637 ILPs were selected. The median overall response rate was 85%, with a median complete response rate of 58.5%. The median overall survival was 38 months, with a 5-year overall survival of 35%. The toxicity was generally mild according to Wieberdink toxicity criteria. Discussion. ILP still offer a high efficacy in selected patients. The main limitation of our review is the heterogeneity and age of most of the articles, as well as the absence of clinical trials comparing ILP with other procedures, making it difficult to transfer its results to the current era. Conclusions. ILP is still an effective and safe procedure for selected patients with unresectable melanoma of the limbs. In the era of targeted therapies and immunotherapy, ILP remains an acceptable and reasonable palliative treatment alternative, especially to avoid limb amputations. The ongoing clinical trials combining systemic therapies and ILP will provide more valuable information in the future to clarify the potential synergism of both strategies

The patient journey : a report of skin cancer care across Europe

Summary - Background: There are poorly documented variations in the journey a skin cancer patient will follow from diagnosis to treatment in the European Union. Objectives: To investigate the possible difficulties or obstacles that a person with a skin malignancy in the European Union may have to overcome in order to receive adequate medical screening and care for his/her condition. In addition, we wished to explore differences in European health systems, which may lead to health inequalities and health inequities within Europe. Methods: Ten European countries took part in this investigation (in alphabetical order): Finland, Germany, Greece, Italy, Malta, Poland, Romania, Spain, the Netherlands and the U.K. The individual participants undertook local and national enquiries within their own country and completed a questionnaire. Results This exercise has identified important differences in the management of a skin cancer patient, reflecting major disparities in health care between European countries. Conclusions: Further investigation of health disparities and efforts to address health inequalities should lead to improvements in European health care quality and reduction in morbidity from skin cancer.This publication arises from the EPIDERM project, which was funded by the European Commission’s Executive Agency for Health and Consumers (EPIDERM project: PHEA 2007- A ⁄100994 HI). Funding for publication of this supplement was provided by the European Skin Cancer Foundation (ESCF).peer-reviewe

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19