Papel de los tejidos orales durante la infección por SARS-CoV-2 / Role of oral tissues in SARS-CoV-2 infection

La actual pandemia de COVID-19 provocada por el virus SARS-CoV-2 es un problema de salud que afecta a la población globalmente. Su desarrollo puede ser asintomático o exhibir manifestaciones clínicas moderadas o severas dependiendo en gran medida de la respuesta inmune de quien la padece. Esta enfermedad afecta principalmente a los pulmones a través del desarrollo del síndrome respiratorio agudo severo (SRAS), tanto como por la «tormenta de citocinas¼, una respuesta inflamatoria exacerbada que podría provocar una falla multisistémica y, en casos severos, la muerte. Se conoce que la enzima convertidora de angiotensina 2 (ECA-2), presente en diversos tejidos del cuerpo, actúa como receptor funcional del virus SARS-CoV-2 facilitando la entrada de éste a las células. Se ha demostrado la presencia de dicho receptor en varios tejidos orales, por lo que se puede considerar a la cavidad bucal como una vía latente de infección por dicho coronavirus, ya que su mecanismo de transmisión es a través de la inhalación de partículas virales, ya sea por vía nasal u oral. Así mismo, la presencia de carga vírica en la saliva y algunos de los síntomas de la COVID-19, por ejemplo la ageusia, pueden indicar la presencia de contagio viral en etapas tempranas. La presente revisión muestra evidencia que sugiere que diversos tejidos en la cavidad oral podrían ser considerados sitios potenciales de contagio por el SARS-CoV-2, teniendo un papel importante en el mecanismo de transmisión y en el desarrollo de coinfecciones (AU)

The COVID-19 pandemic caused by the SARS-CoV-2 virus is currently a global healthcare problem. The onset of this disease can exhibit several clinical manifestations ranging from mild to severe symptoms, depending on the individual's immune response. COVID-19 primarily affects the lungs by developing the Severe Acute Respiratory Syndrome (SARS) and the «cytokine storm¼, an exacerbated inflammatory reaction that can lead to multiorgan failure and consequently death. The angiotensin-converting enzyme 2 (ACE-2), present in several tissues in the human body, is known to act as the functional receptor of the SARS-CoV-2 germ facilitating its entrance into the cells. Such receptor is also present in diverse oral cavity tissues, indicating a latent route of infection due to its influence in the transmission mechanism by inhalation, either oral or nasal, of virus particles. Also, viral load in saliva and taste disorder symptoms like ageusia could indicate a viral infection in its early stages. This article presents evidence suggesting that several tissues in the oral cavity can be considered potential sites of SARS-CoV-2 infection, thus playing an essential role in the transmission mechanism and development of co-infections (AU)

Self-Assembling Peptides as an Emerging Platform for the Treatment of Metabolic Syndrome.

Metabolic syndrome comprises a cluster of comorbidities that represent a major risk of developing chronic diseases, such as type II diabetes, cardiovascular diseases, and stroke. Alarmingly, metabolic syndrome reaches epidemic proportions worldwide. Today, lifestyle changes and multiple drug-based therapies represent the gold standard to address metabolic syndrome. However, such approaches face two major limitations: complicated drug therapeutic regimes, which in most cases could lead to patient incompliance, and limited drug efficacy. This has encouraged scientists to search for novel routes to deal with metabolic syndrome and related diseases. Within such approaches, self-assembled peptide formulations have emerged as a promising alternative for treating metabolic syndrome. In particular, self-assembled peptide hydrogels, either as acellular or cell-load three-dimensional scaffoldings have reached significant relevance in the biomedical field to prevent and restore euglycemia, as well as for controlling cardiovascular diseases and obesity. This has been possible thanks to the physicochemical tunability of peptides, which are developed from a chemical toolbox of versatile amino acids enabling flexibility of designing a wide range of self-assembled/co-assembled nanostructures forming biocompatible viscoelastic hydrogels. Peptide hydrogels can be combined with several biological entities, such as extracellular matrix proteins, drugs or cells, forming functional biologics with therapeutic ability for treatment of metabolic syndrome-comorbidities. Additionally, self-assembly peptides combine safety, tolerability, and effectivity attributes; by this presenting a promising platform for the development of novel pharmaceuticals capable of addressing unmet therapeutic needs for diabetes, cardiovascular disorders and obesity. In this review, recent advances in developing self-assembly peptide nanostructures tailored for improving treatment of metabolic syndrome and related diseases will be discussed from basic research to preclinical research studies. Challenges facing the development of approved medicinal products based on self-assembling peptide nanomaterials will be discussed in light of regulatory requirement for clinical authorization.

Evaluation of the immunogenic capability of the BCG strains BCGΔBCG1419c and BCGΔBCG1416c in a three-dimensional human lung tissue model.

Tuberculosis (TB) still remains as an unmet global threat. The current vaccine is not fully effective and novel alternatives are needed. Here, two vaccine candidate strains derived from BCG carrying deletions in the BCG1416c or BCG1419c genes were analysed for their capacity to modulate the cytokine/chemokine profile and granuloma formation in a human lung tissue model (LTM). We show that the clustering of monocytes, reminiscent of early granuloma formation, in LTMs infected with BCG strains was similar for all of them. However, BCGΔBCG1419c, like M. tuberculosis, was capable of inducing the production of IL-6 in contrast to the other BCG strains. This work suggests that LTM could be a useful ex vivo assay to evaluate the potential immunogenicity of novel TB vaccine candidates.

A Randomized, Double-Blind, Placebo-Controlled Phase II Study of the Efficacy and Safety of Monotherapy Ontuxizumab (MORAb-004) Plus Best Supportive Care in Patients with Chemorefractory Metastatic Colorectal Cancer.

Purpose: The purpose of this study was to evaluate the safety and efficacy of ontuxizumab (MORAb-004), a monoclonal antibody that interferes with endosialin (tumor endothelial marker-1) function, in patients with chemorefractory metastatic colorectal cancer and to identify a responsive patient population based on biomarkers.Experimental Design: This was a randomized, double-blind, placebo-controlled, phase II study. Patients were randomly assigned in a 2:1 ratio to receive weekly intravenous ontuxizumab (8 mg/kg) or placebo plus best supportive care until progression or unacceptable toxicity. Tissue and blood biomarkers were evaluated for their ability to identify a patient population that was responsive to ontuxizumab.Results: A total of 126 patients were enrolled. No significant difference between the ontuxizumab and placebo groups was evident for the primary endpoint of progression-free survival (PFS), with a median PFS of 8.1 weeks in each group (HR, 1.13; 95% confidence interval, 0.76-1.67; P = 0.53). There were no significant differences between groups for overall survival (OS) or overall response rate (ORR). The most common treatment-emergent adverse events (TEAEs) in the ontuxizumab group (vs. the placebo group, respectively) were fatigue (53.7% vs. 47.5%), nausea (39.0% vs. 35.0%), decreased appetite (34.1% vs. 27.5%), and constipation (28.0% vs. 32.5%). The most common grade 3/4 TEAE in the ontuxizumab group versus placebo was back pain (11.0% vs. 0%). No single biomarker clearly identified patients responsive to ontuxizumab.Conclusions: No benefit with ontuxizumab monotherapy compared with placebo for clinical response parameters of PFS, OS, or ORR was demonstrated. Ontuxizumab was well tolerated. Clin Cancer Res; 24(2); 316-25. ©2017 AACR.

Declaración ante los resultados del ensayo clínico Symplicity HTN 3. Grupo de estudio de la hipertensión arterial resistente / Position paper on the results of Symplicity HTN-3 trial. Grupo de estudio de la hipertensión arterial resistente

La denervación de las arterias renales ha sido una alternativa para el tratamiento de la hipertensión arterial resistente. Los estudios Symplicity HTN 1 y 2 mostraron en grupos pequeños y no controlados disminuciones de la presión sistólica hasta de 30 mm Hg. Este entusiasmo ha sido opacado por el estudio Symplicity HTN 3, ensayo clínico aleatorizado y controlado con un procedimiento placebo. Sorprendentemente, los resultados sugirieron que la denervación renal tuvo un efecto similar al del placebo, aunque en el análisis de subgrupos preespecificados los pacientes que no eran de raza negra, los menores de 65 años y los que tenían función renal normal tuvieron una reducción de la presión arterial sistólica estadísticamente significativa. Esta es una evaluación crítica de los resultados del Symplicity HTN 3 y propone posibles explicaciones para estos. Además, declara la postura de nuestro grupo y las acciones futuras.

Renal artery denervation has shown to be an effective treatment for resistant hypertension. Symplicity HTN 1 and 2 trials showed in small and uncontrolled groups, significant systolic blood pressure reductions down to 30 mm Hg. Symplicity HTN-3, a double blind, randomized, placebo controlled clinical trial shaded this initial enthusiasm. Surprisingly, their results showed that renal denervation has a similar effect to placebo. Pre-specified subgroup analysis showed that non-black race individuals, younger than 65 years and with normal renal function, had a statistically significant systolic blood pressure decrease. This manuscript critically appraises the Symplicity HTN-3 trial, proposing possible explanations for the results. Also declares our group position and future actions regarding renal denervation.

Neuroendocrine liver metastasis treated by using intraarterial therapy: volumetric functional imaging biomarkers of early tumor response and survival.

PURPOSE: To determine if volumetric changes of diffusion-weighted and contrast material-enhanced magnetic resonance (MR) imaging can help assess early tumor response to intraarterial therapy (IAT) in neuroendocrine liver metastasis (NELM). MATERIALS AND METHODS: This retrospective single-center comprehensive imaging analysis was performed in compliance with HIPAA and was institutional review board approved. Informed patient consent was waived. Seventy-one patients (39 men; mean age, 62.3 years) with NELM treated with IAT were analyzed retrospectively. MR studies were performed before and 3-4 weeks after therapy. The index lesion was segmented to provide volumetric functional analysis of apparent diffusion coefficient (ADC) and contrast-enhanced MR imaging in the hepatic arterial phase (HAP) and portal venous phase (PVP). Tumor response was defined as increase in volumetric ADC of 15% or greater and decrease in volumetric enhancement of 25% or greater during the HAP or of 50% or greater during the PVP. Patient overall survival was the primary end point after therapy initiation. Univariate analysis included Kaplan-Meier survival curves. The Cox proportional hazards regression model was used to detect interactions between volumetric ADC and contrast-enhanced MR imaging and to calculate the hazard ratio. RESULTS: There was significant increase in mean volumetric ADC (27%, P < .0001) and significant decrease in mean volumetric enhancement during the HAP (-25.3%, P < .0001) and the PVP (-22.4%, P < .0001) in all patients. Patients who had 15% or greater volumetric ADC increase (n = 49) after therapy had better prognosis than those who had less than 15% increase in volumetric ADC (n = 22) (log-rank test, P < .002). Patients who had 25% or greater decrease in volumetric arterial enhancement (n = 40) or 50% or greater decrease in venous enhancement (n = 18) had better prognosis than those who had less than 25% decrease in volumetric arterial enhancement (n = 31) or less than 50% decrease in venous enhancement (n = 53) (log-rank test, P < .02). CONCLUSION: Volumetric functional MR imaging criteria may act as biomarkers of early response, indicating that these criteria may be important to incorporate in future NELM clinical trials.