Bezlotoxumab during the first episode of Clostridioides difficile infection in patients at high risk of recurrence.

PURPOSE: To describe a cohort with a high risk of recurrence who received bezlotoxumab during the first episode of Clostridioides difficile infection (CDI) and to compare this cohort with patients with similar characteristics who did not receive the monoclonal antibody. METHODS: A prospective and multicentre study of patients with a high risk of recurrence (expected recurrence rate>35%) who were treated with bezlotoxumab during their first episode of CDI was conducted. A propensity score-matched model 1:2 was used to compare both cohorts that were weighed according to basal characteristics (hospital-acquisition, creatinine value, and fidaxomicin as a CDI treatment). RESULTS: Sixty patients (mean age:72 years) were prospectively treated with bezlotoxumab plus anti-Clostridioides antibiotic therapy. Vancomycin (48 patients) and fidaxomicin (12 patients) were prescribed for CDI treatment, and bezlotoxumab was administered at a mean of 4.2 (SD:2.1) days from the beginning of therapy. Recurrence occurred in nine out of 54 (16.7%) evaluable patients at 8 weeks. Forty bezlotoxumab-treated patients were matched with 69 non-bezlotoxumab-treated patients. Recurrence rates at 12 weeks were 15.0% (6/40) in bezlotoxumab-treated patients vs. 23.2% (16/69) in non-bezlotoxumab-treated patients (OR:0.58 [0.20-1.65]). No adverse effects were observed related to bezlotoxumab infusion. Only one of 9 patients with previous heart failure developed heart failure. CONCLUSION: We observed that patients treated with bezlotoxumab in a real-world setting during a first episode of CDI having high risk of recurrence, presented low rate of recurrence. However, a significant difference in recurrence could not be proved in comparison to the controls. We did not detect any other safety concerns.

Unraveling the Potential of miRNAs from CSCs as an Emerging Clinical Tool for Breast Cancer Diagnosis and Prognosis.

Breast cancer (BC) is the most diagnosed cancer in women and the second most common cancer globally. Significant advances in BC research have led to improved early detection and effective therapies. One of the key challenges in BC is the presence of BC stem cells (BCSCs). This small subpopulation within the tumor possesses unique characteristics, including tumor-initiating capabilities, contributes to treatment resistance, and plays a role in cancer recurrence and metastasis. In recent years, microRNAs (miRNAs) have emerged as potential regulators of BCSCs, which can modulate gene expression and influence cellular processes like BCSCs' self-renewal, differentiation, and tumor-promoting pathways. Understanding the miRNA signatures of BCSCs holds great promise for improving BC diagnosis and prognosis. By targeting BCSCs and their associated miRNAs, researchers aim to develop more effective and personalized treatment strategies that may offer better outcomes for BC patients, minimizing tumor recurrence and metastasis. In conclusion, the investigation of miRNAs as regulators of BCSCs opens new directions for advancing BC research through the use of bioinformatics and the development of innovative therapeutic approaches. This review summarizes the most recent and innovative studies and clinical trials on the role of BCSCs miRNAs as potential tools for early diagnosis, prognosis, and resistance.

The lived experience of depression: a bottom-up review co-written by experts by experience and academics.

We provide here the first bottom-up review of the lived experience of depression, co-written by experts by experience and academics. First-person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of depression, family members and carers, representing a global network of organizations. The material was enriched by phenomenologically informed perspectives and shared with all collaborators in a cloud-based system. The subjective world of depression was characterized by an altered experience of emotions and body (feeling overwhelmed by negative emotions, unable to experience positive emotions, stuck in a heavy aching body drained of energy, detached from the mind, the body and the world); an altered experience of the self (losing sense of purpose and existential hope, mismatch between the past and the depressed self, feeling painfully incarcerated, losing control over one's thoughts, losing the capacity to act on the world; feeling numb, empty, non-existent, dead, and dreaming of death as a possible escape route); and an altered experience of time (experiencing an alteration of vital biorhythms, an overwhelming past, a stagnation of the present, and the impossibility of the future). The experience of depression in the social and cultural context was characterized by altered interpersonal experiences (struggling with communication, feeling loneliness and estrangement, perceiving stigma and stereotypes), and varied across different cultures, ethnic or racial minorities, and genders. The subjective perception of recovery varied (feeling contrasting attitudes towards recovery, recognizing recovery as a journey, recognizing one's vulnerability and the need for professional help), as did the experience of receiving pharmacotherapy, psychotherapy, and social as well as physical health interventions. These findings can inform clinical practice, research and education. This journey in the lived experience of depression can also help us to understand the nature of our own emotions and feelings, what is to believe in something, what is to hope, and what is to be a living human being.

Vitamin D deficiency and SARS­CoV­2 infection: A retrospective case-Control study with big-data analysis covering March 2020 to March 2021.

BACKGROUND: Vitamin D may have immunomodulatory functions, and might therefore play a role in the pathogenesis of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, no conclusive evidence exists regarding its impact on the prevalence of this infection, the associated course of disease, or prognosis. OBJECTIVE: To study the association between SARS-CoV-2 infection and vitamin D deficiency in patients attending a tertiary university hospital, and to examine the clinical course of infection and prognosis for these patients. METHODS: This non-interventional, retrospective study, which involved big-data analysis and employed artificial intelligence to capture data from free text in the electronic health records of patients diagnosed with SARS-CoV-2, was undertaken at a tertiary university hospital in Madrid, Spain, between March 2020 and March 2021. The variables recorded were vitamin D deficiency, sociodemographic and clinical characteristics, course of disease, and prognosis. RESULTS: Of the 143,157 patients analysed, 36,261 had SARS-CoV-2 infection (25.33%) during the study period, among whom 2,588 (7.14%) had a vitamin D deficiency. Among these latter patients, women (OR 1.45 [95%CI 1.33-1.57]), adults over 80 years of age (OR 2.63 [95%CI 2.38-2.91]), people living in nursing homes (OR 2.88 [95%CI 2.95-3.45]), and patients with walking dependence (OR 3.45 [95%CI 2.85-4.26]) appeared in higher proportion. After adjusting for confounding factors, a higher proportion of subjects with SARS-CoV-2 plus vitamin D deficiency required hospitalisation (OR 1.38 [95%CI 1.26-1.51]), and had a longer mean hospital stay (3.94 compared to 2.19 days in those with normal levels; P = 0.02). CONCLUSION: A low serum 25(OH) vitamin D concentration in patients with SARS-CoV-2 infection is significantly associated with a greater risk of hospitalisation and a longer hospital stay. Among such patients, higher proportions of institutionalised and dependent people over 80 years of age were detected.

Interferon-Alpha Decreases Cancer Stem Cell Properties and Modulates Exosomes in Malignant Melanoma.

Malignant melanoma (MM) can spread to other organs and is resistant in part due to the presence of cancer stem cell subpopulations (CSCs). While a controversial high dose of interferon-alpha (IFN-α) has been used to treat non-metastatic high-risk melanoma, it comes with undesirable side effects. In this study, we evaluated the effect of low and high doses of IFN-α on CSCs by analyzing ALDH activity, side population and specific surface markers in established and patient-derived primary cell lines. We also assessed the clonogenicity, migration and tumor initiation capacities of IFN-α treated CSCs. Additionally, we investigated genomic modulations related to stemness properties using microRNA sequencing and microarrays. The effect of IFN-α on CSCs-derived exosomes was also analyzed using NanoSight and liquid chromatography (LC-HRMS)-based metabolomic analysis, among others. Our results showed that even low doses of IFN-α reduced CSC formation and stemness properties, and led to a significant decrease in the ability to form tumors in mice xenotransplants. IFN-α also modulated the expression of genes and microRNAs involved in several cancer processes and metabolomics of released exosomes. Our work suggests the utility of low doses of interferon, combined with the analysis of metabolic biomarkers, as a potential clinical approach against the aggressiveness of CSCs in melanoma.

Biofabrication of a tri-layered 3D-bioprinted CSC-based malignant melanoma model for personalized cancer treatment.

Conventionalin vitrocancer models do not accurately reproduce the tumor microenvironment (TME), so three-dimensional (3D)-bioprinting represents an excellent tool to overcome their limitations. Here, two multicellular tri-layered malignant melanoma (MM) models composed by cancer stem cells (CSCs) isolated from a MM established cell line or a primary-patient derived cell line, fibroblasts, mesenchymal stem cells, and endothelial cells, embedded within an agarose-collagen type I hydrogel were bioprinted. Embedded-cells showed high proliferation and metabolic activity, and actively remodeled their TME. MM hydrogels displayed similar rheological properties that skin and were able to support an early onset of vascularization. Besides, MM hydrogels displayed different response to vemurafenib compared with cell cultures, and supported tumorigenesis in murine xenotransplant achieving more mimeticin vivomodels. For the first time a tri-layered 3D-bioprinted CSC-based human MM model is developed recreating TMEin vitroandin vivoand response to treatment, being useful for precision treatment regimens against MM.

Chondro-Inductive b-TPUe-Based Functionalized Scaffolds for Application in Cartilage Tissue Engineering.

Osteoarthritis is a disease with a great socioeconomic impact and mainly affects articular cartilage, a tissue with reduced self-healing capacity. In this work, 3D printed 1,4 butanediol thermoplastic polyurethane (b-TPUe) scaffolds are functionalized and infrapatellar mesenchymal stem cells are used as the cellular source. Since b-TPUe is a biomaterial with mechanical properties similar to cartilage, but it does not provide the desired environment for cell adhesion, scaffolds are functionalized with two methods, one based on collagen type I and the other in 1-pyrenebutiric acid (PBA) as principal components. Alamar Blue and confocal assays display that PBA functionalized scaffolds support higher cell adhesion and proliferation for the first 21 days. However, collagen type I functionalization induces higher proliferation rates and similar cell viability than the PBA method. Further, both functionalization methods induce extracellular matrix synthesis, and the presence of chondrogenic markers (Sox9, Col2a, and Acan). Finally, SEM images probe that functionalized 3D printed scaffolds present much better cell/biomaterial interactions than controls and confirm early chondrogenesis. These results indicate that the two methods of functionalization in the highly hydrophobic b-TPUe enhance the cell-biomaterial interactions and the improvement in the chondro-inductive properties, which have great potential for application in cartilage tissue engineering.

Biofabrication approaches and regulatory framework of metastatic tumor-on-a-chip models for precision oncology.

The complexity of the tumor microenvironment (TME) together with the development of the metastatic process are the main reasons for the failure of conventional anticancer treatment. In recent years, there is an increasing need to advance toward advanced in vitro models of cancer mimicking TME and simulating metastasis to understand the associated mechanisms that are still unknown, and to be able to develop personalized therapy. In this review, the commonly used alternatives and latest advances in biofabrication of tumor-on-chips, which allow the generation of the most sophisticated and optimized models for recapitulating the tumor process, are presented. In addition, the advances that have allowed these new models in the area of metastasis, cancer stem cells, and angiogenesis are summarized, as well as the recent integration of multiorgan-on-a-chip systems to recapitulate natural metastasis and pharmacological screening against it. We also analyze, for the first time in the literature, the normative and regulatory framework in which these models could potentially be found, as well as the requirements and processes that must be fulfilled to be commercially implemented as in vitro study model. Moreover, we are focused on the possible regulatory pathways for their clinical application in precision medicine and decision making through the generation of personalized models with patient samples. In conclusion, this review highlights the synergistic combination of three-dimensional bioprinting systems with the novel tumor/metastasis/multiorgan-on-a-chip systems to generate models for both basic research and clinical applications to have devices useful for personalized oncology.

Experiencia con el uso de dalbavancina en la infección profunda de pie diabético / Experience in the use of dalbavancin in diabetic foot infection

Objetivo: Describir la experiencia clínica con dalbavancina en el tratamiento de la infección de pie diabético en una unidad multidisciplinar de un hospital de segundo nivel. Métodos: Estudio descriptivo retrospectivo de pacientes con infección de pie diabético tratados con dalbavancina en la Unidad de Pie Diabético del Hospital Universitario Fundación Alcorcón de septiembre de 2016 a diciembre de 2019. Se recogieron parámetros demográficos y comorbilidades, características de la infección y del tratamiento con dalbavancina. Se estimó la tasa de curación a los 90 días tras finalizar el tratamiento. Resultados: Un total de 23 pacientes con infección de pie diabético (osteomielitis) fueron tratados con dalbavancina; 19 eran hombres con una edad media de 65 años. Los microorganismos más frecuentemente aislados fueron Staphylococcus aureus (11) y Corynebacterium striatum (7). En 22 casos se usó dalbavancina como terapia de segunda elección, en 11 debido a toxicidad de otros antibióticos. La mediana de duración del tratamiento fue de 5 (4-7) semanas; la dosis más frecuente de dalbavancina (8 pacientes) fue de 1.000mg seguido de 500mg semanales durante 5 semanas. Tres pacientes presentaron efectos secundarios leves (náuseas y molestias gastrointestinales). A los 90 días de finalizar el tratamiento, el 87% (20) de los pacientes se curaron (IC95%: 65,2-94,52%). Conclusión: Los pacientes con osteomielitis por microorganismos grampositivos que recibieron como parte del tratamiento multidisciplinar antibioterapia con dalbavancina tuvieron una elevada tasa de curación, con una adecuada tolerancia y escasos efectos secundarios. Dalbavancina ofrece una alternativa segura en el tratamiento de la infección profunda de pie diabético.(AU)

Objective: To describe the clinical experience with dalbavancin in the treatment of diabetic foot infection in a multidisciplinary unit of a second level hospital. Methods: A retrospective, descriptive study was made with all patients with diabetic foot infection treated with dalbavancin in the Diabetic Foot Unit of Hospital Universitario Fundación Alcorcón, covering the period from September 2016 to December 2019. Demographic parameters and comorbidities, characteristics of the infection and treatment with dalbavancin were recorded. The cure rate was estimated at 90 days after finishing the treatment. Results: A total of 23 patients with diabetic foot infection (osteomyelitis) started treatment with dalbavancin, 19 were men and the mean age was 65 years. The microorganisms most frequently isolated for the indication of treatment with dalbavancin were Staphylococcus aureus (11) and Corynebacterium striatum (7). Dalbavancin was used as a second choice therapy in 22 cases, in 11 due to toxicity from other antibiotics. The median duration of treatment was 5 (4-7) weeks; the most frequent dose of dalbavancin (8 patients) was 1000mg followed by 500mg weekly for 5 weeks. 3 patients presented mild side effects (nausea and gastrointestinal discomfort). At 90 days after completion of dalbavancin therapy, 87% (20) of the patients were cured (95% CI: 65.2%-94.52%). Conclusion: Patients with osteomyelitis due to gram-positive microorganisms who received as part of the multidisciplinary antibiotic treatment with dalbavancin, had a high rate of cure with adequate tolerance and few side effects. Dalbavancin offers a safe alternative in treating deep diabetic foot infection.(AU)

Experience in the use of dalbavancin in diabetic foot infection.

OBJECTIVE: To describe the clinical experience with dalbavancin in the treatment of diabetic foot infection in a multidisciplinary unit of a second level hospital. METHODS: A retrospective, descriptive study was made with all patients with diabetic foot infection treated with dalbavancin in the Diabetic Foot Unit of Hospital Universitario Fundación Alcorcón, covering the period from September 2016 to December 2019. Demographic parameters and comorbidities, characteristics of the infection and treatment with dalbavancin were recorded. The cure rate is estimated at 90 days after finishing the treatment. RESULTS: A total of 23 patients with diabetic foot infection (osteomyelitis) started treatment with dalbavancin, 19 were men and the mean age was 65 years. The microorganisms most frequently isolated for the indication of treatment with dalbavancin were Staphylococcus aureus (11) and Corynebacterium striatum (7). Dalbavancin was used as a second choice therapy in 22 cases, in 11 due to toxicity from other antibiotics. The median duration of treatment was 5 (4-7) weeks; the most frequent dose of dalbavancin (8 patients) was 1000 mg followed by 500 mg weekly for 5 weeks. 3 patients presented mild side effects (nausea and gastrointestinal discomfort). At 90 days after completion of dalbavancin therapy, 87% (20) of the patients were cured (95% CI: 65.2%-94.52%). CONCLUSION: Patients with osteomyelitis due to gram-positive microorganisms who received as part of the multidisciplinary antibiotic treatment with dalbavancin, had a high rate of cure with adequate tolerance and few side effects. Dalbavancin offers a safe alternative in treating deep diabetic foot infection.

Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial.

We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers.

The biomimetic extracellular matrix: a therapeutic tool for breast cancer research.

BACKGROUND: A deeper knowledge of the functional versatility and dynamic nature of the ECM has improved the understanding of cancer biology. Translational Significance: This work provides an in-depth view of the importance of the ECM to develop more mimetic breast cancer models, which aim to recreate the components and architecture of tumor microenvironment. Special focus is placed on decellularized matrices derived from tissue and cell culture, both in procurement and applications, as they have achieved great success in cancer research and pharmaceutical sector. The extracellular matrix (ECM) is increasingly recognized as a master regulator of cell behavior and response to breast cancer (BC) treatment. During BC progression, the mammary gland ECM is remodeled and altered in the composition and organization. Accumulated evidence suggests that changes in the composition and mechanics of ECM, orchestrated by tumor-stromal interactions along with ECM remodeling enzymes, are actively involved in BC progression and metastasis. Understanding how specific ECM components modulate the tumorigenic process has led to an increased interest in the development of biomaterial-based biomimetic ECM models to recapitulate key tumor characteristics. The decellularized ECMs (dECMs) have emerged as a promising in vitro 3D tumor model, whose recent advances in the processing and application could become the biomaterial by excellence for BC research and the pharmaceutical industry. This review offers a detailed view of the contribution of ECM in BC progression, and highlights the application of dECM-based biomaterials as promising personalized tumor models that more accurately mimic the tumorigenic mechanisms of BC and the response to treatment. This will allow the design of targeted therapeutic approaches adapted to the specific characteristics of each tumor that will have a great impact on the precision medicine applied to BC patients.

Evolution of Metastasis Study Models toward Metastasis-On-A-Chip: The Ultimate Model?

For decades, several attempts have been made to obtain a mimetic model for the study of metastasis, the reason of most of deaths caused by cancer, in order to solve the unknown phenomena surrounding this disease. To better understand this cellular dissemination process, more realistic models are needed that are capable of faithfully recreating the entire and essential tumor microenvironment (TME). Thus, new tools known as tumor-on-a-chip and metastasis-on-a-chip have been recently proposed. These tools incorporate microfluidic systems and small culture chambers where TME can be faithfully modeled thanks to 3D bioprinting. In this work, a literature review has been developed about the different phases of metastasis, the remaining unknowns and the use of new models to study this disease. The aim is to provide a global vision of the current panorama and the great potential that these systems have for in vitro translational research on the molecular basis of the pathology. In addition, these models will allow progress toward a personalized medicine, generating chips from patient samples that mimic the original tumor and the metastatic process to perform a precise pharmacological screening by establishing the most appropriate treatment protocol.

Development of a Biomimetic Hydrogel Based on Predifferentiated Mesenchymal Stem-Cell-Derived ECM for Cartilage Tissue Engineering.

The use of decellularized extracellular matrix (dECM) as a biomaterial has been an important step forward for the development of functional tissue constructs. In addition to tissues and organs, cell cultures are gaining a lot of attention as an alternative source of dECM. In this work, a novel biomimetic hydrogel is developed based on dECM obtained from mesenchymal stem cells (mdECM) for cartilage tissue engineering. To this end, cells are seeded under specific culture conditions to generate an early chondrogenic extracellular matrix (ECM) providing cues and elements necessary for cartilage development. The composition is determined by quantitative, histological, and mass spectrometry techniques. Moreover, the decellularization process is evaluated by measuring the DNA content and compositional analyses, and the hydrogel is formulated at different concentrations (3% and 6% w/v). Results show that mdECM derived hydrogels possess excellent biocompatibility and suitable physicochemical and mechanical properties for their injectability. Furthermore, it is evidenced that this hydrogel is able to induce chondrogenesis of mesenchymal stem cells (MSCs) without supplemental factors and, furthermore, to form hyaline cartilage-like tissue after in vivo implantation. These findings demonstrate for the first time the potential of this hydrogel based on mdECM for applications in cartilage repair and regeneration.

Efectividad de los glucocorticoides en pacientes hospitalizados por neumonía grave por SARS-CoV-2 / Effectiveness of glucocorticoids in patients hospitalized for severe SARS-CoV-2 pneumonia

Introducción: Se han comunicado varios trabajos donde se ha demostrado un efecto beneficioso de los glucocorticoides como tratamiento de la tormenta de citocinas que se asocia a los cuadros graves por SARS-CoV-2, plateándose diferentes pautas de glucocorticoides.MétodosEstudio observacional retrospectivo que incluye pacientes con neumonía grave por SARS-CoV-2 y compara el ingreso en una unidad de cuidados intensivos (UCI) o fallecimiento durante la hospitalización en 3 grupos de pacientes: sin tratamiento con glucocorticoides, uso de dosis diarias de glucocorticoides equivalentes menores a 250mg de prednisona y dosis diarias equivalentes mayores o iguales a 250mg de prednisona. Se realizó un análisis multivariante mediante regresión logística, utilizando el índice de propensión como covariante.ResultadosDe los 259 pacientes incorporados al estudio 67 (25,9%) tuvieron una evolución desfavorable, falleciendo o precisando ingreso en UCI. Los análisis comparativos entre diferentes tratamientos con glucocorticoides, y la asociación con ingreso en UCI o fallecimiento fueron: tratamiento con glucocorticoides (cualquier dosis) versus sin tratamiento con glucocorticoides (OR: 0,71 [0,30-1,66]), tratamiento con glucocorticoides (≥250mg de prednisona al día) versus sin tratamiento con glucocorticoides (OR: 0,35 [0,11-1,08]) y tratamiento con glucocorticoides (≥250mg de prednisona al día) versus pacientes con dosis de glucocorticoides<250mg de prednisona o sin tratamiento con glucocorticoides (OR: 0,30 [0,10-0,88]).ConclusiónLos resultados de este estudio muestran que los paciente con neumonía grave por SARS-CoV-2 tratados con pulsos con glucocorticoides con dosis equivalentes de prednisona mayor o igual de 250mg tienen una evolución más favorable (menos mortalidad e ingreso en UCI). (AU)

Introduction: Several studies have reported the beneficial effect of glucocorticoids in the treatment of cytokine storm that occurs in patients with severe COVID-19. Various glucocorticoids regimens have been proposed.MethodsRetrospective observational study that includes patients with severe SARS-CoV-2 pneumonia and compares admission to an Intensive Care Unit (ICU) or death during hospitalization in three groups of patients: no glucocorticoids treatment, use of glucocorticoids doses equivalent to less than 250mg of prednisone daily and use of equivalent doses greater than or equal to 250mg of prednisone daily. Multivariate analysis was performed using logistic regression, using the propensity index as a covariant.ResultsOf the 259 patients enrolled in the study, 67 (25.9%) had an unfavorable evolution, dying or requiring ICU admission. Comparative analyzes between different glucocorticoids treatments and the association with ICU admission or death were: glucocorticoids treatment (any dose) versus no glucocorticoids treatment (OR: 0.71 [0.30-1.66]), treatment with glucocorticoids (≥250mg prednisone daily) versus no glucocorticoids treatment (OR: 0.35 [0.11-1.08]) and glucocorticoids treatment (≥250mg prednisone daily) versus patients with glucocorticoids doses <250mg prednisone daily or without glucocorticoids treatment (OR: 0.30 [0.10-0.88]).ConclusionThe results of this study show that patients with severe SARS-CoV-2 pneumonia treated with glucocorticoids pulses with equivalent doses of prednisone greater than or equal to 250mg have a more favorable evolution (less mortality and less admission to ICU). (AU)

Validation of the 1,4-butanediol thermoplastic polyurethane as a novel material for 3D bioprinting applications.

Tissue engineering (TE) seeks to fabricate implants that mimic the mechanical strength, structure, and composition of native tissues. Cartilage TE requires the development of functional personalized implants with cartilage-like mechanical properties capable of sustaining high load-bearing environments to integrate into the surrounding tissue of the cartilage defect. In this study, we evaluated the novel 1,4-butanediol thermoplastic polyurethane elastomer (b-TPUe) derivative filament as a 3D bioprinting material with application in cartilage TE. The mechanical behavior of b-TPUe in terms of friction and elasticity were examined and compared with human articular cartilage, PCL, and PLA. Moreover, infrapatellar fat pad-derived human mesenchymal stem cells (MSCs) were bioprinted together with scaffolds. in vitro cytotoxicity, proliferative potential, cell viability, and chondrogenic differentiation were analyzed by Alamar blue assay, SEM, confocal microscopy, and RT-qPCR. Moreover, in vivo biocompatibility and host integration were analyzed. b-TPUe demonstrated a much closer compression and shear behavior to native cartilage than PCL and PLA, as well as closer tribological properties to cartilage. Moreover, b-TPUe bioprinted scaffolds were able to maintain proper proliferative potential, cell viability, and supported MSCs chondrogenesis. Finally, in vivo studies revealed no toxic effects 21 days after scaffolds implantation, extracellular matrix deposition and integration within the surrounding tissue. This is the first study that validates the biocompatibility of b-TPUe for 3D bioprinting. Our findings indicate that this biomaterial can be exploited for the automated biofabrication of artificial tissues with tailorable mechanical properties including the great potential for cartilage TE applications.

Effectiveness of glucocorticoids in patients hospitalized for severe SARS-CoV-2 pneumonia.

BACKGROUND: Several studies have reported the beneficial effect of glucocorticoids in the treatment of cytokine storm that occurs in patients with severe COVID-19. Various glucocorticoids regimens have been proposed. METHODS: Retrospective observational study that includes patients with severe SARS-CoV-2 pneumonia and compares admission to an Intensive Care Unit (ICU) or death during hospitalization in three groups of patients: no glucocorticoids treatment, use of glucocorticoids doses equivalent to less than 250 mg of prednisone daily and use of equivalent doses greater than or equal to 250 mg of prednisone daily. Multivariate analysis was performed using logistic regression, using the propensity index as a covariant. RESULTS: Of the 259 patients enrolled in the study, 67 (25.9%) had an unfavorable evolution, dying or requiring ICU admission. Comparative analyzes between different glucocorticoids treatments and the association with ICU admission or death were: glucocorticoids treatment (any dose) versus no glucocorticoids treatment (OR: 0.71 [0.30-1.66]), treatment with glucocorticoids (≥250 mg prednisone daily) versus no glucocorticoids treatment (OR: 0.35 [0.11-1.08]) and glucocorticoids treatment (≥250 mg prednisone daily) versus patients with glucocorticoids doses <250 mg prednisone daily or without glucocorticoids treatment (OR: 0.30 [0.10-0.88]). CONCLUSION: The results of this study show that patients with severe SARS-CoV-2 pneumonia treated with glucocorticoids pulses with equivalent doses of prednisone greater than or equal to 250 mg have a more favorable evolution (less mortality and less admission to ICU).

INTRODUCCIÓN: Se han comunicado varios trabajos donde se ha demostrado un efecto beneficioso de los glucocorticoides como tratamiento de la tormenta de citocinas que se asocia a los cuadros graves por SARS-CoV-2, plateándose diferentes pautas de glucocorticoides. MÉTODOS: Estudio observacional retrospectivo que incluye pacientes con neumonía grave por SARS-CoV-2 y compara el ingreso en una unidad de cuidados intensivos (UCI) o fallecimiento durante la hospitalización en 3 grupos de pacientes: sin tratamiento con glucocorticoides, uso de dosis diarias de glucocorticoides equivalentes menores a 250 mg de prednisona y dosis diarias equivalentes mayores o iguales a 250 mg de prednisona. Se realizó un análisis multivariante mediante regresión logística, utilizando el índice de propensión como covariante. RESULTADOS: De los 259 pacientes incorporados al estudio 67 (25,9%) tuvieron una evolución desfavorable, falleciendo o precisando ingreso en UCI. Los análisis comparativos entre diferentes tratamientos con glucocorticoides, y la asociación con ingreso en UCI o fallecimiento fueron: tratamiento con glucocorticoides (cualquier dosis) versus sin tratamiento con glucocorticoides (OR: 0,71 [0,30­1,66]), tratamiento con glucocorticoides (≥250 mg de prednisona al día) versus sin tratamiento con glucocorticoides (OR: 0,35 [0,11­1,08]) y tratamiento con glucocorticoides (≥250 mg de prednisona al día) versus pacientes con dosis de glucocorticoides < 250 mg de prednisona o sin tratamiento con glucocorticoides (OR: 0,30 [0,10­0,88]). CONCLUSIÓN: Los resultados de este estudio muestran que los paciente con neumonía grave por SARS-CoV-2 tratados con pulsos con glucocorticoides con dosis equivalentes de prednisona mayor o igual de 250 mg tienen una evolución más favorable (menos mortalidad e ingreso en UCI).

Experience in the use of dalbavancin in diabetic foot infection. / Experiencia con el uso de dalbavancina en la infección profunda de pie diabético.

OBJECTIVE: To describe the clinical experience with dalbavancin in the treatment of diabetic foot infection in a multidisciplinary unit of a second level hospital. METHODS: A retrospective, descriptive study was made with all patients with diabetic foot infection treated with dalbavancin in the Diabetic Foot Unit of Hospital Universitario Fundación Alcorcón, covering the period from September 2016 to December 2019. Demographic parameters and comorbidities, characteristics of the infection and treatment with dalbavancin were recorded. The cure rate was estimated at 90 days after finishing the treatment. RESULTS: A total of 23 patients with diabetic foot infection (osteomyelitis) started treatment with dalbavancin, 19 were men and the mean age was 65 years. The microorganisms most frequently isolated for the indication of treatment with dalbavancin were Staphylococcus aureus (11) and Corynebacterium striatum (7). Dalbavancin was used as a second choice therapy in 22 cases, in 11 due to toxicity from other antibiotics. The median duration of treatment was 5 (4-7) weeks; the most frequent dose of dalbavancin (8 patients) was 1000mg followed by 500mg weekly for 5 weeks. 3 patients presented mild side effects (nausea and gastrointestinal discomfort). At 90 days after completion of dalbavancin therapy, 87% (20) of the patients were cured (95% CI: 65.2%-94.52%). CONCLUSION: Patients with osteomyelitis due to gram-positive microorganisms who received as part of the multidisciplinary antibiotic treatment with dalbavancin, had a high rate of cure with adequate tolerance and few side effects. Dalbavancin offers a safe alternative in treating deep diabetic foot infection.

[Effectiveness of glucocorticoids in patients hospitalized for severe SARS-CoV-2 pneumonia]. / Efectividad de los glucocorticoides en pacientes hospitalizados por neumonía grave por SARS-CoV-2.

INTRODUCTION: Several studies have reported the beneficial effect of glucocorticoids in the treatment of cytokine storm that occurs in patients with severe COVID-19. Various glucocorticoids regimens have been proposed. METHODS: Retrospective observational study that includes patients with severe SARS-CoV-2 pneumonia and compares admission to an Intensive Care Unit (ICU) or death during hospitalization in three groups of patients: no glucocorticoids treatment, use of glucocorticoids doses equivalent to less than 250mg of prednisone daily and use of equivalent doses greater than or equal to 250mg of prednisone daily. Multivariate analysis was performed using logistic regression, using the propensity index as a covariant. RESULTS: Of the 259 patients enrolled in the study, 67 (25.9%) had an unfavorable evolution, dying or requiring ICU admission. Comparative analyzes between different glucocorticoids treatments and the association with ICU admission or death were: glucocorticoids treatment (any dose) versus no glucocorticoids treatment (OR: 0.71 [0.30-1.66]), treatment with glucocorticoids (≥250mg prednisone daily) versus no glucocorticoids treatment (OR: 0.35 [0.11-1.08]) and glucocorticoids treatment (≥250mg prednisone daily) versus patients with glucocorticoids doses <250mg prednisone daily or without glucocorticoids treatment (OR: 0.30 [0.10-0.88]). CONCLUSION: The results of this study show that patients with severe SARS-CoV-2 pneumonia treated with glucocorticoids pulses with equivalent doses of prednisone greater than or equal to 250mg have a more favorable evolution (less mortality and less admission to ICU).

The Inhibitory Role of miR-486-5p on CSC Phenotype Has Diagnostic and Prognostic Potential in Colorectal Cancer.

Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second cause of cancer deaths. Increasing evidences supports the idea that the poor prognosis of patients is related to the presence of cancer stem cells (CSCs), a cell population able to drive cancer recurrence and metastasis. The deregulation of microRNAs (miRNAs) plays a role in the formation of CSC. We investigated the role of hsa-miR-486-5p (miR-486-5p) in CRC, CSCs, and metastasis, in order to reach a better understanding of the biomolecular and epigenetic mechanisms mir-486-5p-related. The expression of miR-486-5p was investigated in three different matrices from CRC patients and controls and in CSCs obtained from the CRC cell lines HCT-116, HT-29, and T-84. In the human study, miR-486-5p was up-regulated in serum and stool of CRC patients in comparison with healthy controls but down-regulated in tumor tissue when compared with normal mucosa. miR-486-5p was also down-regulated in the sera of metastatic patients. In vitro, miR-486-5p was down-regulated in CSC models and it induced an inhibitory effect on stem factors and oncogenes in the main pathways of CSCs. Our results provide a step forward in understanding the role of mir-486-5p in CRC and CSC, and suggest that further studies are needed to investigate its diagnostic and prognostic power, possibly in combination with other biomarkers.