Immunomodulation of T Helper Cells by Tumor Microenvironment in Oral Cancer Is Associated With CCR8 Expression and Rapid Membrane Vitamin D Signaling Pathway.

The immune system plays a key role in the protective response against oral cancer; however, the tumor microenvironment (TME) impairs this anti-cancer response by modulating T helper (Th) responses and promoting an anti-inflammatory environment. Regulatory T cells (Tregs) and Th2 effector cells (Teff) are associated with poor prognosis in oral squamous cell carcinoma (OSCC). However, the main immunomodulatory mechanisms associated with the enrichment of these subsets in OSCC remain unknown. We characterized Th-like lineages in Tregs and Teff and evaluated immunomodulatory changes induced by the TME in OSCC. Our phenotypic data revealed a higher distribution of tumour-infiltrating CCR8+ and Th2-like Treg in OSCC compared with non-malignant samples, whereas the percentages of Th1 cells were reduced in cancer. We then analyzed the direct effect of the TME by exposing T cell subsets to cancer secretomes and observed the OSCC secretome induced CCR8 expression and reduced cytokine production from both subsets. Transcriptomic analysis showed that the co-culture with OSCC secretome induced several gene changes associated with the vitamin D (VitD) signaling pathway in T cells. In addition, proteomic analysis identified the presence of several proteins associated with prostaglandin E2 (PGE2) production by rapid membrane VitD signaling and a reduced presence of the VitD binding protein. Thus, we analyzed the effect of VitD and PGE2 and observed that VitD promotes a regulatory Th2-like response with CCR8 expression whilst PGE2 also modulated CCR8 but inhibited cytokine production in combination with VitD. Finally, we evaluated the presence of CCR8 ligand in OSCC and observed increased chemokine CCL18, which was also able to upregulate CCR8 in activated Th cells. Overall, our data showed the immunomodulatory changes induced by the TME involving CCR8 expression and regulatory Th2 phenotypes, which are associated with PGE2 mediated VitD signaling pathway and CCL18 expression in OSCC.

Evaluación del desempeño del APACHE II y SAPS III, en una unidad de cuidados intensivos / Performance evaluation of APACHE II and SAPS III in an intensive care unit / Avaliação de desempenho do APACHE II e SAPS III, em unidade de terapia intensiva

RESUMEN Objetivo El objetivo principal de este trabajo, fue validar y comparar la capacidad predictiva de mortalidad de los indicadores de gravedad APACHE II (Acute Physiology and Chronic Health Evaluation, Score II) y SAPS III (Simplified Acute Physiology, Score III) en una muestra de pacientes admitidos en la Unidad de Cuidados Intensivos Adulto (UCI) del Hospital de Curicó, entre los años 2011 y 2013. Materiales y Métodos Estudio analítico, observacional de cohorte histórica de casos consecutivos desde la admisión a la UCI hasta el egreso hospitalario. Para el análisis, se usó el Modelo de Regresión Logística Binaria. De un total de 1 042 pacientes ingresados a la UCI, se incluyó a 793 pacientes sobrevivientes, y a 249 pacientes fallecidos, que representaban el 76,1% y 23,9% respectivamente, del total. Resultados El SAPS III presenta mejor capacidad predictiva que el APACHE II, según el área bajo la curva de características operativas del receptor 0,81 y 0,80 respectivamente. La sensibilidad para el modelo SAPS III es 0,95 y para APACHE II es 0,93. El índice de especificidad es 0,3 para el SAPS III y 0,4 para el APACHE II, con probabilidad superior a 0,5. Conclusión Los indicadores de predicción de mortalidad en UCI; APACHE II y SAPS III tienen una buena capacidad predictiva general, pero ambos indicadores presentan una baja especificidad.(AU)

ABSTRACT Objective The main objective of this work was to validate and compare the predictive capacity of mortality of the severity score systems APACHE II (Acute Physiology and Chronic Health Evaluation, Score II) and SAPS III (Simplified Acute Physiology, Score III) in a sample of patients admitted to the Adult Intensive Care Unit (ICU) of the Hospital de Curicó between 2011 and 2013. Materials and Methods Analytical, observational, retrospective cohort study of consecutive cases since admission to the ICU until hospital discharge. A binary logistic regression model was used for the analysis. Out of 1 042 patients admitted to the ICU, 793 surviving patients and 249 deceased patients were included, representing 76.1% and 23.9%, respectively, of the total sample. Results The SAPS III score has a better predictive capacity than the APACHE II, according to the area under the curve and the receiver operating characteristic curve: 0.81 and 0.80, respectively. Sensitivity for the SAPS III model was 0.95 and for APACHE II was 0.93. The specificity index was 0.3 for SAPS III and 0.4 for APACHE II, with a probability above 0.5. Conclusion APACHE II and SAPS III, as ICU mortality prediction indicators, have a good predictive power but low specificity.(AU)

RESUMO Objetivo O objetivo principal deste trabalho foi validar e comparar a capacidade preditiva de mortalidade dos sistemas de escore de gravidade APACHE II (Fisiologia Aguda e Avaliação Crônica de Saúde, Escore II) e SAPS III (Fisiologia Aguda Simplificada, Escore III) em uma amostra de pacientes internado na Unidade de Terapia Intensiva Adulto (UTI) do Hospital de Curicó entre 2011 e 2013. Materiais e métodos Estudo de coorte analítico, observacional e retrospectivo de casos consecutivos desde a admissão na UTI até a alta hospitalar. Um modelo de regressão logística binária foi usado para a análise. Dos 1.042 pacientes admitidos na UTI, foram incluídos 793 pacientes sobreviventes e 249 falecidos, representando 76,1% e 23,9%, respectivamente, do total da amostra. Resultados O escore SAPS III tem melhor capacidade preditiva do que o APACHE II, de acordo com a área sob a curva e a curva de característica de operação do receptor: 0,81 e 0,80, respectivamente. A sensibilidade para o modelo SAPS III foi de 0,95 e para APACHE II foi de 0,93. O índice de especificidade foi de 0,3 para SAPS III e 0,4 para APACHE II, com probabilidade superior a 0,5. Conclusão APACHE II e SAPS III, como indicadores de predição de mortalidade em UTI, apresentam bom poder preditivo, mas baixa especificidade.(AU)

[Performance evaluation of APACHE II and SAPS III in an intensive care unit]. / Evaluación del desempeño del APACHE II y SAPS III, en una unidad de cuidados intensivos.

OBJECTIVE: The main objective of this work was to validate and compare the predictive capacity of mortality of the severity score systems APACHE II (Acute Physiology and Chronic Health Evaluation, Score II) and SAPS III (Simplified Acute Physiology, Score III) in a sample of patients admitted to the Adult Intensive Care Unit (ICU) of the Hospital de Curicó between 2011 and 2013. MATERIALS AND METHODS: Analytical, observational, retrospective cohort study of consecutive cases since admission to the ICU until hospital discharge. A binary logistic regression model was used for the analysis. Out of 1 042 patients admitted to the ICU, 793 surviving patients and 249 deceased patients were included, representing 76.1% and 23.9%, respectively, of the total sample. RESULTS: The SAPS III score has a better predictive capacity than the APACHE II, according to the area under the curve and the receiver operating characteristic curve: 0.81 and 0.80, respectively. Sensitivity for the SAPS III model was 0.95 and for APACHE II was 0.93. The specificity index was 0.3 for SAPS III and 0.4 for APACHE II, with a probability above 0.5. CONCLUSION: APACHE II and SAPS III, as ICU mortality prediction indicators, have a good predictive power but low specificity.

OBJETIVO: El objetivo principal de este trabajo, fue validar y comparar la capacidad predictiva de mortalidad de los indicadores de gravedad APACHE II (Acute Physiology and Chronic Health Evaluation, Score II) y SAPS III (Simplified Acute Physiology, Score III) en una muestra de pacientes admitidos en la Unidad de Cuidados Intensivos Adulto (UCI) del Hospital de Curicó, entre los años 2011 y 2013. MATERIALES Y MÉTODOS: Estudio analítico, observacional de cohorte histórica de casos consecutivos desde la admisión a la UCI hasta el egreso hospitalario. Para el análisis, se usó el Modelo de Regresión Logística Binaria. De un total de 1 042 pacientes ingresados a la UCI, se incluyó a 793 pacientes sobrevivientes, y a 249 pacientes fallecidos, que representaban el 76,1% y 23,9% respectivamente, del total. RESULTADOS: El SAPS III presenta mejor capacidad predictiva que el APACHE II, según el área bajo la curva de características operativas del receptor 0,81 y 0,80 respectivamente. La sensibilidad para el modelo SAPS III es 0,95 y para APACHE II es 0,93. El índice de especificidad es 0,3 para el SAPS III y 0,4 para el APACHE II, con probabilidad superior a 0,5. CONCLUSIÓN: Los indicadores de predicción de mortalidad en UCI; APACHE II y SAPS III tienen una buena capacidad predictiva general, pero ambos indicadores presentan una baja especificidad.

Laparoscopic hemicolectomy for a patient with situs inversus totalis and colorectal cancer / Colectomia laparóscopica para um paciente com situs inversus totalis e câncer colorretal

ABSTRACT Situs inversus totalis is a congenital anatomic anomaly characterized by a complete inversion of thoracic and abdominal organs. We present a case of a 67 year-old patient diagnosed with situs inversus totals in his childhood who was referred for a two-month history of hematoquezia. Ascending colon cancer where found and he underwent a laparoscopic hemicolectomy with radical lymphadenectomy. An exhaustive preoperative study and a detailed planning of laparoscopic surgery including positions of operator and assistants and trocar sites have been performed to be aware of anatomic challenges. The operating time was 120 min and blood loss was minimal. Histologic examination showed a well-differentiated adenocarcinoma with serosal invasion and without lymph nodes metastasis (pT3N0). The patient was discharged on postoperative 6th day without complications. Laparoscopic surgery for colon cancer in patients with situs inversus totalis could be more difficult nevertheless a safe and feasible procedure should be performed successfully.

RESUMO Situs inversus totalis é uma anomalia anatómica consistindo em um investimento de órgãos abdominais. Nesse estudo, descrevemos um paciente, homem 67 anos, que foi diagnosticado com situs inversus totalis na infância. Apresentava sintomas de sangramento retal e foi diagnosticado com câncer de cólon direito e tratado cirurgicamente com receção laparoscópica. Para a realização da colectomia laparoscopica precisamos de um estudo pré-operatória completa e um plano detalhado de cirurgia com localização do trocateres e cirurgiões. A cirurgia durou 120 minutos e perde de sangue foi mínima. O resultado do exame patológico relatou adenocarcinoma (T3N0). Nosso paciente foi admitido por 7 dias e não apresentaram complicações. Para os pacientes com situs inversus totalis e câncer colorretal a receção laparoscópica pode ser mais difícil mas eficaz e segura.

Implantes pterigoideos, una opción de tratamiento / Pterygoid implants: a treatment option

El edentulismo parcial en el sector posterior del hueso maxilar, es producido principalmente por la pérdida de molares debido a caries, enfermedad periodontal y al exceso de fuerza soportado por losdientes de este sector. Implantes dentales mayores a 10 mm, raramente son colocados en estas zona debido auna mayor probabilidad de fracasos por el escaso volumen óseo y deficiente calidad del hueso. En el cráneo, en relación posterior a la maxila encontramos un arbotante pterigomaxilar. Este permite, en algunas situaciones, la rehabilitación de maxilares atróficos mediante la colocación de implantes con una angulación parasinusal, evitando técnicas quirúrgicas o procedimiento más complejos. El implante pterigoideo es un posible tratamiento para rehabilitar el sector posterior del maxilar atrófico, anclado en hueso cortical del proceso pterigoides. Se reporta un caso de utilización de implantes pterigoídeos en una mujer de 58 años de edad con gran neumatización en ambos senos maxilares, con un remanente de hueso alveolar de 1-2 mm.

The partially edentulous in the posterior maxilla bone is produced mainly by the loss of molars due to caries, periodontal disease and excessive force supported by the teeth of this sector. Dental implants greater than 10 mm, are rarely placed in this area due to a higher probability of failure for the low bone volume and bone quality poor. In the skull, in the post jawbone relationship, we find a pterygomaxillary buttress. This allows, in some situations, the rehabilitation of atrophic jaws by placing implants with a parasinusal angulation, avoiding surgical techniques or more complex procedure. The pterygoid implant is a possible treatment to rehabilitate the atrophic posterior maxilla, anchored in cortical bone of the pterygoid process. A case of placement of pterygoid implants in a woman 58 years old with a large pneumatization in both maxillary sinuses, with a remaining alveolar bone 1-2 mm is reported.

Técnicas de injerto óseo alveolar en fisura labio alveolo palatina. Revisión de la literatura / Techniques of alveolar bone grafting in cleft lip and palate. Literature review

La fisura labio-palatina es una de las malformaciones congénitas más comunes de la región orofacial, y puede incidir significativamente en la calidad de vida de los afectados. El tratamiento integral de estos pacientes es complejo e incluye el uso de injerto óseo alveolar, para restaurar la morfología y función normal de los arcos. El objetivo de este trabajo fue describir las características de las diversas técnicas de injerto alveolar que aún son objeto de controversia. La osteoplastía secundaria es el enfoque más ampliamente aceptado, y consiste en la realización del injerto alveolar durante la dentición mixta, entre los 9 y 12 años, antes de la erupción del canino permanente, pues la disponibilidad de hueso es más predecible en este período, a la vez que proporcionaría el apoyo periodontal adecuado para la erupción y la preservación de los dientes adyacentes a la hendidura. La literatura señala que el hueso esponjoso autólogo fresco es el estándar de oro para este procedimiento, ya que proporciona las células óseas inmunocompatibles necesarias; pero estudios más recientes han señalado una superioridad del injerto córtico-medular, además del uso complementario de rhBMP-2. De la misma manera, se señala que la cresta iliaca corresponde al sitio dador más promovido, aunque la calota craneal puede representar una opción igual o aún más efectiva y con un menor nivel de morbilidad postoperatoria. Es necesario continuar explorando las alternativas mencionadas y promover la investigación en búsqueda de nuevas opciones, incluyendo avances en la ingeniería tisular.

The lip and palatal cleft is one of the most common congenital malformations of the buccal-facial region and can significantly impact the quality of life of the affected people. The comprehensive treatment of these patients is complex and includes the use of alveolar bone graft to restore the normal dental arches morphology and function. The aim of this article was describing the features of several alveolar grafting techniques which are still controversial. The secondary osteoplasty is the most widely accepted approach and it is the implementation of the alveolar graft during the mixed dentition, at the ages between 9 and 12 years, before the eruption of the permanent canine tooth, because the bone availability is more predictable in this period, while it would provide an adequate periodontal support for the eruption and preservation of the teeth adjacent to the cleft. The literature indicates that fresh autologous cancellous bone is the golden rule for this procedure because it provides the necessary immunocompatible bone cells; but more recent studies have shown the superiority of cortico-medullar graft, besides the complementary use of rhBMP-2. Similarly, it is noted that the iliac crest is the most recommended donor site, although the skull graft may represent the same or even more effective option and with a lower level of post surgery morbidity. It is necessary to continue exploring such alternatives and promoting research for new options, including advances in tissue engineering.

The biomechanical role of scaffolds in augmented rotator cuff tendon repairs.

BACKGROUND: Scaffolds continue to be developed and used for rotator cuff repair augmentation; however, the appropriate scaffold material properties and/or surgical application techniques for achieving optimal biomechanical performance remains unknown. The objectives of the study were to simulate a previously validated spring-network model for clinically relevant scenarios to predict: (1) the manner in which changes to components of the repair influence the biomechanical performance of the repair and (2) the percent load carried by the scaffold augmentation component. MATERIALS AND METHODS: The models were parametrically varied to simulate clinically relevant scenarios, namely, changes in tendon quality, altered surgical technique(s), and different scaffold designs. The biomechanical performance of the repair constructs and the percent load carried by the scaffold component were evaluated for each of the simulated scenarios. RESULTS: The model predicts that the biomechanical performance of a rotator cuff repair can be modestly increased by augmenting the repair with a scaffold that has tendon-like properties. However, engineering a scaffold with supraphysiologic stiffness may not translate into yet stiffer or stronger repairs. Importantly, the mechanical properties of a repair construct appear to be most influenced by the properties of the tendon-to-bone repair. The model suggests that in the clinical setting of a weak tendon-to-bone repair, scaffold augmentation may significantly off-load the repair and largely mitigate the poor construct properties. CONCLUSIONS: The model suggests that future efforts in the field of rotator cuff repair augmentation may be directed toward strategies that strengthen the tendon-to-bone repair and/or toward engineering scaffolds with tendon-like mechanical properties.

Determinación y análisis de costos reales de tratamientos intensivos por paciente y día cama / Analysis of real costs of intensive treatments per patient and bed/day

El objetivo del trabajo es medir los costos reales asociados a las patologías tratadas en las Unidades de Cuidados Intensivos Adulto de los Hospitales Públicos de la Región del Maule, y compararlos con el costo asignado por Fonasa al día cama para el año 2011. Materiales y métodos: Se trata de un estudio prospectivo, aplicando el Sistema de Costos Basado en Actividades (ABC). Se incluyó 469 pacientes, 222 pacientes de la Unidad de Cuidados Intensivos del Hospital de Curicó y 247 pacientes la Unidad de Cuidados Intensivos del Hospital de Talca entre el 01 de enero y 30 de agosto de 2011, los que de acuerdo a edad y APACHE, representan los niveles de complejidad de pacientes de Unidades de Cuidados Intensivos a nivel nacional. Los pacientes se clasificaron según las patologías: sepsis, cardiovascular, respiratorias, neurológicas, trauma, digestivos, renales y otros. Resultados: Las patologías que presentan mayor mediana de costos por día cama son: sepsis ($362.115), respiratorias ($352.793), trauma ($348.442), renales ($341.928) y cardiovascular ($291.061). La estructura de costos del día cama está conformada principalmente por el costo asociado al recurso humano, cuyo valor máximo asciende a 64 por ciento, seguido del costo asociado a los medicamentos con un valor máximo de 15 por ciento. Los pacientes con sepsis y trauma absorben la mayor proporción de recursos en la Unidad de Cuidados Intensivos en estudio; 35 por ciento y 19 por ciento respectivamente y una proporción significativa de dichos costos es utilizada por pacientes que fallecen (34 por ciento y 19 por ciento) respectivamente. Conclusión: Todas las patologías en estudio tienen desviación desfavorable de costos, con respecto al arancel fijado por Fonasa, que sólo asciende a $192.160, para el año 2011.

The aim of the study is measures the real costs associated with the pathologies treated in the of Intensive Care Unid (ICU) Adults of the Public Hospitals of the region of the Maule, and to compare them with the cost assigned by Fonasa to the bed/day for the year 2011. Materials and methods: it is a question of a market study, applying the Activity-based costing (ABC). There was included 469 patients, 222 patients of the ICU of the Curicó’s Hospital and 247 patients the ICU of the Talca’s Hospital between January 01 and August 30, 2011, which in agreement to age and APACHE II, represent the levels of patients’ complexity of ICU to national level. The patients qualified according to the pathologies: sepsis, cardiovascular, respiratory, neurological, trauma, digestive, renal and others. Results: The pathologies that present major median of costs per day bed are: sepsis ($362.115), respiratory ($352.793),trauma ($348.442), renal ($341.928) and cardiovascular ($291.061). The structure of costs of the day bed is shaped principally by the cost associated with the human resource, which maximum value promotes 64 percent, followed by the cost associated with the medicines with a maximum value of 15 percent. The patients with sepsis and trauma absorbed the major proportion of resources in the ICU in our study; 35 percent and 19 percent respectively and a significant proportion of the abovementioned costs is used by patients who die (34 percent and 19 percent)respectively. Conclusion: All the pathologies in study have unfavorable diversion of costs, with regard to the duty fixed by Fonasa, which only promotes to $192.160, for the year2011.

[Gastrointestinal and mesenteric injuries in the trauma patient: incidence, diagnosis delay and prognosis]. / Lesiones gastrointestinales y mesentéricas en el paciente politraumatizado: incidencia, demora diagnóstica y pronóstico.

BACKGROUND: Gastrointestinal and mesenteric injuries (GIMI) are uncommon in trauma patients, and their diagnosis are often delayed. Our aims were to determine the reliability of CT scan in our centre, and to assess the clinical significance of a delayed diagnosis. MATERIALS AND METHOD: Retrospective analysis of cases confirmed at laparotomy. Patients were identified at the Severe Trauma Registry of Gregorio Marañón University General Hospital, between 1993 and 2006. RESULTS: We found 105 (16.6%) GIMI out of 632 patients with abdominal trauma, in a Registry with 1495 severe trauma cases included. A total of 46% had blunt injuries. The mean injury severity score (ISS) and new ISS (NISS) were 20 and 25, respectively. There were 9 (8.5%) deaths, 4 of which were unexpected. A CT scan was performed in 56 (53%) cases, and only in 37 there were signs suggestive of a GIMI. In another 43 (41%) patients an urgent laparotomy was indicated because of positive clinical findings or instability. Surgery was delayed for more than 8 hours in 21 (20%) patients, the most common reason being a false negative result in the CT scan. CONCLUSIONS: The overall incidence of GIMI was high in our centre (31% due to penetration and 10.7% blunt trauma). Several factors, such as the initial lack of symptoms, a low diagnostic sensitivity of the CT scan (34% false negatives), and the non-surgical management of solid organ injuries, have contributed to a delayed diagnosis and treatment in one out of each five patients in our series, but this has not led to a significant increase in septic complications in this group.

Oxygen diffusion through natural extracellular matrices: implications for estimating "critical thickness" values in tendon tissue engineering.

Oxygen is necessary for maintaining cell proliferation and viability and extracellular matrix (ECM) production in 3-dimensional tissue engineering. Typically, diffusion is the primary mode for oxygen transport in vitro; thus, ensuring an adequate oxygen supply is essential. In this study, we determined the oxygen diffusion coefficients of 3 natural ECMs that are being investigated as construct scaffolds for tendon tissue engineering: small-intestine submucosa (SIS), human dermis (Alloderm), and canine fascia lata. Diffusion coefficients were determined using a standard diffusion cell system. The ranges for each matrix type were: SIS: 7 x 10(-6) - 2 x 10(-5) cm2/s, Alloderm: 1.9 - 3.1 x 10(-5) cm2/s, and canine fascia lata: 1.6 - 4 x 10(-5) cm2/s. We used the experimental oxygen diffusivity data for these natural ECMs in a mathematical model of oxygen diffusion through a cell-seeded scaffold to estimate the critical size of cell-seeded scaffold that can be cultured in vitro.