Effect of Dentin Irrigants on Push-Out Bond Strength in Resin Cementation Protocols for Fiber Posts in Endodontically Treated Teeth: An In Vitro Study.

The aim of this study is to analyze the effects of different endodontic irrigants and adhesive systems on the resin bond strength of fiber post cementation. In total, 144 single-rooted, unrestored human teeth were endodontically treated and randomly divided into 12 groups according to four endodontic irrigants (distilled water as control; EDTA 17%; NaOCl 5%; chlorhexidine digluconate 2%) and three different adhesive/resin cement systems (etch-and-rinse: orthophosphoric acid, Parabond® A+B/Paracore®; self-etch: ParaBond® Non-Rinse Conditioner, Parabond® A+B/Paracore®; Universal: ClearfilTM Universal Bond/ClearfilTM DC Core Plus). Forty-eight hours after post cementation, ten teeth from each group were cross-sectioned into three discs (cervical, middle and apical regions). Thirty specimens of each group (n = 30) were submitted to a push-out test at a crosshead speed of 1 mm/min. The remaining two teeth of each group were sectioned in the same manner, and the resin-dentin interface was evaluated using scanning electron microscopy (SEM). The results were statistically analyzed with the ANOVA test and Tukey's test (p < 0,01). The adhesive protocols and post space region showed no significant effect on bond strength (p > 0.01). The combination of NaOCl 5% and ClearfilTM Universal Bond reduced the adhesive strength (p < 0.01). The NaOCl 5%, in relation to other irrigants, significantly decreased the push-out bond strength.

Natural history and comorbidities of generalised and partial lipodystrophy syndromes in Spain.

The rarity of lipodystrophies implies that they are not well-known, leading to delays in diagnosis/misdiagnosis. The aim of this study was to assess the natural course and comorbidities of generalised and partial lipodystrophy in Spain to contribute to their understanding. Thus, a total of 140 patients were evaluated (77.1% with partial lipodystrophy and 22.9% with generalised lipodystrophy). Clinical data were collected in a longitudinal setting with a median follow-up of 4.7 (0.5-17.6) years. Anthropometry and body composition studies were carried out and analytical parameters were also recorded. The estimated prevalence of all lipodystrophies in Spain, excluding Köbberling syndrome, was 2.78 cases/million. The onset of phenotype occurred during childhood in generalised lipodystrophy and during adolescence-adulthood in partial lipodystrophy, with the delay in diagnosis being considerable for both cohorts. There are specific clinical findings that should be highlighted as useful features to take into account when making the differential diagnosis of these disorders. Patients with generalised lipodystrophy were found to develop their first metabolic abnormalities sooner and a different lipid profile has also been observed. Mean time to death was 83.8 ± 2.5 years, being shorter among patients with generalised lipodystrophy. These results provide an initial point of comparison for ongoing prospective studies such as the ECLip Registry study.

Recurrent Glioblastoma: A Review of the Treatment Options.

Glioblastoma is a disease with a poor prognosis. Multiple efforts have been made to improve the long-term outcome, but the 5-year survival rate is still 5-10%. Recurrence of the disease is the usual way of progression. In this situation, there is no standard treatment. Different treatment options can be considered. Among them would be reoperation or reirradiation. There are different studies that have assessed the impact on survival and the selection of patients who may benefit most from these strategies. Chemotherapy treatments have also been considered in several studies, mainly with alkylating agents, with data mostly from phase II studies. On the other hand, multiple studies have been carried out with target-directed treatments. Bevacizumab, a monoclonal antibody with anti-angiogenic activity, has demonstrated activity in several studies, and the FDA has approved it for this indication. Several other TKI drugs have been evaluated in this setting, but no clear benefit has been demonstrated. Immunotherapy treatments have been shown to be effective in other types of tumors, and several studies have evaluated their efficacy in this disease, both immune checkpoint inhibitors, oncolytic viruses, and vaccines. This paper reviews data from different studies that have evaluated the efficacy of different forms of relapsed glioblastoma.

Current Landscape of Immunotherapy for Advanced Sarcoma.

There is substantial heterogeneity between different subtypes of sarcoma regarding their biological behavior and microenvironment, which impacts their responsiveness to immunotherapy. Alveolar soft-part sarcoma, synovial sarcoma and undifferentiated pleomorphic sarcoma show higher immunogenicity and better responses to checkpoint inhibitors. Combination strategies adding immunotherapy to chemotherapy and/or tyrosine-kinase inhibitors globally seem superior to single-agent schemes. Therapeutic vaccines and different forms of adoptive cell therapy, mainly engineered TCRs, CAR-T cells and TIL therapy, are emerging as new forms of immunotherapy for advanced solid tumors. Tumor lymphocytic infiltration and other prognostic and predictive biomarkers are under research.

Receptor Tyrosine Kinase Inhibitors for the Treatment of Recurrent and Unresectable Bone Sarcomas.

Bone sarcomas are a heterogeneous group of rare tumors with a predominance in the young population. Few options of systemic treatment are available once they become unresectable and resistant to conventional chemotherapy. A better knowledge of the key role that tyrosine kinase receptors (VEGFR, RET, MET, AXL, PDGFR, KIT, FGFR, IGF-1R) may play in the pathogenesis of these tumors has led to the development of multi-target inhibitors (TKIs) that are progressively being incorporated into our therapeutic arsenal. Osteosarcoma (OS) is the most frequent primary bone tumor and several TKIs have demonstrated clinical benefit in phase II clinical trials (cabozantinib, regorafenib, apatinib, sorafenib, and lenvatinib). Although the development of TKIs for other primary bone tumors is less advanced, preclinical data and early trials have begun to show their potential benefit in advanced Ewing sarcoma (ES) and rarer bone tumors (chondrosarcoma, chordoma, giant cell tumor of bone, and undifferentiated pleomorphic sarcoma). Previous reviews have mainly provided information on TKIs for OS and ES. We aim to summarize the existing knowledge regarding the use of TKIs in all bone sarcomas including the most recent studies as well as the potential synergistic effects of their combination with other systemic therapies.

Prognostic value of circulating endothelial cells in glioblastoma patients: a pilot study.

Aim: Glioblastoma (GB) is an aggressive tumor type and the detection of circulating endothelial cells (CECs) in peripheral blood has been related to angiogenesis. Materials & methods: A prospective single-center pilot study of CEC detection at diagnosis in 22 patients with GB was performed, using the US FDA-approved CellSearch system. Results: A CEC cutoff value was estimated using a receiver operating curve (ROC) and patients were classified into two groups: <40 CEC/4 ml and >40 CEC/4 ml blood. Median overall survival was 25.33 months for group 1 and 8.23 months for group 2 cases (p = 0.02). There was no correlation between CEC and PWI (perfusion-weighted imaging) RM. Conclusion: CEC detection has a prognostic value in GB cases at diagnosis.

Risk Factors of Mortality in Hospitalized Patients With COVID-19 Applying a Machine Learning Algorithm.

Introduction: Risk stratification of patients with COVID-19 can be fundamental to support clinical decision-making and optimize resources. The objective of our study is to identify among the routinely tested clinical and analytical parameters those that would allow us to determine patients with the highest risk of dying from COVID-19. Material and methods: We carried out a retrospective cohort multicentric study by consecutively, including hospitalized patients with COVID-19 admitted in any of the 11 hospitals in the healthcare network of HM Hospitals-Spain. We collected the clinical, demographic, analytical, and radiological data from the patient's medical records.To assess each of the biomarkers' predictive impact and measure the statistical significance of the variables involved in the analysis, we applied a random forest with a permutation method. We used the similarity measure induced by a previously classification model and adjusted the k-groups clustering algorithm based on the energy distance to stratify patients into a high and low-risk group. Finally, we adjusted two optimal classification trees to have a schematic representation of the cut-off points. Results: We included 1246 patients (average age of 65.36 years, 62% males). During the study one hundred sixty-eight patients (13%) died. High values of age, D-Dimer, White Blood Cell, Na, CRP, and creatinine represent the factors that identify high-risk patients who would die. Conclusions: Age seems to be the primary predictor of mortality in patients with SARS-CoV-2 infection, while the impact of acute phase reactants and blood cellularity is also highly relevant.

Introducción: La estratificación del riesgo de los pacientes con COVID-19 puede ser fundamental para apoyar la toma de decisiones clínicas y optimizar los recursos. El objetivo de nuestro estudio es identificar, entre los parámetros clínicos y analíticos probados de forma rutinaria, aquellos que nos permitirían determinar a los pacientes con mayor riesgo de morir por COVID-19. Material y métodos: Se realizó un estudio multicéntrico de cohorte retrospectiva de forma consecutiva, incluyendo pacientes hospitalizados con COVID-19 ingresados en cualquiera de los 11 hospitales de la red sanitaria de HM Hospitales-España.Los datos clínicos, demográficos, analíticos y radiológicos se recopilaron de las historias clínicas de los pacientes.Para evaluar el impacto predictivo de cada uno de los biomarcadores y medir la significación estadística de las variables involucradas en el análisis, se aplicó un bosque aleatorio con un método de permutación. Utilizamos la medida de similitud inducida por un modelo de clasificación previo, y ajustamos el algoritmo de agrupación de grupos k en función de la distancia de energía para estratificar a los pacientes en un grupo de alto y bajo riesgo. Finalmente, ajustamos 2 árboles de clasificación óptimos para tener una representación esquemática de los puntos de corte. Resultados: Se incluyeron 1.246 pacientes (edad promedio de 65,36 años, 62% varones). Durante el estudio murieron 168 pacientes (13%). Los factores que identifican a los pacientes de alto riesgo de mortalidad son los valores elevados de edad, dímero D, glóbulos blancos, Na, PCR y creatinina. Conclusiones: La edad parece ser el principal predictor de mortalidad en pacientes con infección por SARS-CoV-2, mientras que el impacto de los reactantes de fase aguda y la celularidad sanguínea también es muy relevante.

Influence of operator expertise on glide path and root canal preparation of curved root canals with rotary and reciprocating motions.

This study intended to help practitioners selecting the appropriate motion according to their level of expertise for glide path and complete root canal preparation of curved canals in terms of instrument fracture and preparation time. A total of 160 curved root canals (angle >30°, radius <6 mm) were allocated randomly to 4 groups: A/B for expert operators and C/D for nonexpert operators. A/C were shaped with rotary and B/D with reciprocating instruments. Preparation time was registered and compared with Kruskal-Wallis non-parametric test and Dunn's post hoc test. Instrument separation was also registered and compared with chi-square test. A fractographic analysis was performed with scanning electron microscopy. The use of reciprocation motions allowed nonexpert operators to avoid instrument breakage during glide path and to prepare root canals faster. Experts were equally effective in rotary/reciprocating root canal shaping and faster with rotary motions than nonexpert operators, who also fractured significantly more rotary instruments.

Efficacy of continuous apical negative ultrasonic irrigation (CANUI) in penetration of simulated lateral canals in extracted teeth.

The aim of this study was to evaluate the efficacy of continuous apical negative ultrasonic irrigation into simulated lateral canals and the apical third in straight and curved root canals. Two simulated lateral canals were created 2, 4 and 6 mm from the working length in 120 single-rooted teeth (6 canals/tooth, n = 360 straight, n = 360 curved). The teeth were randomly divided into 3 experimental groups: positive pressure irrigation (PPI) (n = 20); passive ultrasonic irrigation (PUI) (n = 20); continuous apical negative ultrasonic irrigation (CANUI) (n = 20). 20% Chinese ink was added to a 5% sodium hypochlorite solution and delivered into the root canals. The results showed a significantly higher (P < 0.05) penetration of irrigant into the lateral canals and up to working length in the CANUI group for straight and curved roots. CANUI improves penetration into the lateral canals and up to the working length of the cleared teeth in straight and curved roots.

Indoor Radon in EGFR- and BRAF-Mutated and ALK-Rearranged Non-Small-Cell Lung Cancer Patients.

BACKGROUND: Radon gas is the leading cause of lung cancer in the nonsmoking population. The World Health Organization (WHO) recommends indoor concentrations of < 100 Bq/m³. Several molecular alterations have been described in non-small-cell lung cancer (NSCLC), mainly in nonsmokers, with no risk factors identified. We studied the role of indoor radon in NSCLC patients harboring specific driver alterations. PATIENTS AND METHODS: We assessed the radon concentration from EGFR-, BRAF-mutated (m), and ALK-rearranged (r) NSCLC patients measured by an alpha-track detector placed in their homes between September 2014 and August 2015. Clinical characteristics were collected prospectively, and pathologic samples were reviewed retrospectively. RESULTS: Forty-eight patients were included (36 EGFRm, 10 ALKr, 2 BRAFm). Median radon concentration was 104 Bq/m³ (IQR 69-160) overall, and was 96 Bq/m³ (42-915) for EGFRm, 116 (64-852) for ALKr, and 125 for BRAFm, with no significant differences. Twenty-seven patients (56%) had indoor radon above WHO recommendations, 8 (80%) of 10 ALKr, 2 (100%) of 2 BRAFm, and 17 (47%) of 36 EGFRm. CONCLUSION: The median indoor radon concentration was above the WHO recommendations, with no differences between EGFR, ALK, and BRAF patients. Concentrations above the WHO recommendations were most common with ALKr and BRAFm. These findings should be validated in larger studies.

Enrichment of rare genetic variants in astrocyte gene enriched co-expression modules altered in postmortem brain samples of schizophrenia.

The transcriptome profiles of the cingulate gyrus region from the postmortem brain tissues of a set of well-characterized patients with schizophrenia (SCZ) and matched controls were investigated using an integrated approach that analyzed both the alterations in transcription expression pattern and rare genetic variants in expressed genes. We demonstrated increased expression of astrocyte-related genes using spatiotemporal co-expression modules that have previously been established for developing human brain, and showed these results are independent of medication dosage. The relationship between genetic variants and expression pattern in the context of neurodevelopment was further investigated, and we identified an enrichment of rare genetic variants in a set of signature genes that were specific to astrocytes and up-regulated in the patients with SCZ. Our result suggested the involvement of astrocyte malfunction in SCZ pathophysiology. In addition, our approach indicated a novel strategy of narrowing down genetic variants that might contribute to the pathophysiology in the patients with SCZ to a subset of genes that are highly expressed in an affected brain region.

Gastrostomy vs nasogastric tube feeding in patients with head and neck cancer during radiotherapy alone or combined chemoradiotherapy

INTRODUCTION: Patients with head and neck cancer (HNC) submitted to radiotherapy alone or combined chemoradiotherapy present a high prevalence of malnutrition at baseline. Prophylactic use of gastrostomy has been suggested for these patients for delivering enteral nutrition. On the other hand, other authors have failed to demonstrate the effectiveness of this measure over nasogastric tube feeding. MATERIAL AND METHODS: We studied 40 patients with HNC with moderate or severe malnutrition who were offered either prophylactic percutaneous gastrostomy before starting oncologic treatment or close follow-up with nutritional counseling with the placement of a nasogastric tube when necessary. RESULTS: There were no significant changes throughout the study period in weight (p = 0.338), body mass index (BMI) (p = 0.314) or serum proteins (p = 0.729), and these changes showed no differences between the gastrostomy vsnasogastric tube feeding groups. The amount of delivered energy was above the estimated energy needs with both gastrostomy and nasogastric tube feeding, but there were no differences in the total energy provided by enteral nutrition between groups. Patients in the gastrostomy group received enteral nutrition support for a longer period of time (p = 0.007). CONCLUSIONS: Both gastrostomy and nasogastric tube feeding are effective methods of delivering enteral nutrition in patients with HNC submitted to radiotherapy alone or combined chemoradiotherapy, with no differences between them in terms of avoiding further nutritional deterioration.

Gastrostomy vs nasogastric tube feeding in patients with head and neck cancer during radiotherapy alone or combined chemoradiotherapy / Gastrostomía o sonda nasogástrica en pacientes con cáncer de cabeza y cuello durante la radioterapia o tratamiento combinado con quimiorradioterapia

Introduction: Patients with head and neck cancer (HNC) submitted to radiotherapy alone or combined chemoradiotherapy present a high prevalence of malnutrition at baseline. Prophylactic use of gastrostomy has been suggested for these patients for delivering enteral nutrition. On the other hand, other authors have failed to demonstrate the effectiveness of this measure over nasogastric tube feeding. Material and methods: We studied 40 patients with HNC with moderate or severe malnutrition who were offered either prophylactic percutaneous gastrostomy before starting oncologic treatment or close follow-up with nutritional counseling with the placement of a nasogastric tube when necessary. Results: There were no significant changes throughout the study period in weight (p = 0.338), body mass index (BMI) (p = 0.314) or serum proteins (p = 0.729), and these changes showed no differences between the gastrostomy vs nasogastric tube feeding groups. The amount of delivered energy was above the estimated energy needs with both gastrostomy and nasogastric tube feeding, but there were no differences in the total energy provided by enteral nutrition between groups. Patients in the gastrostomy group received enteral nutrition support for a longer period of time (p = 0.007). Conclusions: Both gastrostomy and nasogastric tube feeding are effective methods of delivering enteral nutrition in patients with HNC submitted to radiotherapy alone or combined chemoradiotherapy, with no differences between them in terms of avoiding further nutritional deterioration (AU)

Introducción: los pacientes con cáncer de cabeza y cuello (CCC) que reciben radioterapia o tratamiento combinado con radioterapia y quimioterapia presentan una elevada prevalencia de desnutrición. El uso profiláctico de la gastrostomía se ha sugerido para el soporte nutricional enteral en estos pacientes. Sin embargo, otros autores no han demostrado un beneficio claro de esta medida frente al uso de la sonda nasogástrica. Material y métodos: se realizó el estudio en cuarenta pacientes con CCC con desnutrición moderada o grave, a los cuales se les ofreció la gastrostomía percutánea antes de empezar el tratamiento oncológico o bien seguimiento estrecho mediante consejo nutricional y la colocación de una sonda nasogástrica en el momento necesario. Resultados: no se encontraron cambios significativos en cuanto a peso, (p = 0,338), índice de masa corporal (p = 0,314) o proteínas séricas (p= 0,729) durante el seguimiento, y estos cambios tampoco fueron diferentes entre los pacientes con gastrostomía o con sonda nasogástrica. Las calorías recibidas fueron superiores a los requerimientos estimados en ambos grupos, pero no existieron diferencias entre ellos. Los pacientes con gastrostomía recibieron nutrición enteral durante más tiempo (p = 0,007). Conclusiones: tanto la gastrostomía como la sonda nasogástrica son eficaces para el soporte nutricional enteral en pacientes con CCC que reciben radioterapia o tratamiento combinado con quimioterapia y radioterapia, sin mostrar diferencias en la evolución nutricional entre ambas (AU)