MAPK11 (p38ß) is a major determinant of cellular radiosensitivity by controlling ionizing radiation-associated senescence: An in vitro study.

Background and purpose: MAPKs are among the most relevant signalling pathways involved in coordinating cell responses to different stimuli. This group includes p38MAPKs, constituted by 4 different proteins with a high sequence homology: MAPK14 (p38α), MAPK11 (p38ß), MAPK12 (p38γ) and MAPK13 (p38δ). Despite their high similarity, each member shows unique expression patterns and even exclusive functions. Thus, analysing protein-specific functions of MAPK members is necessary to unequivocally uncover the roles of this signalling pathway. Here, we investigate the possible role of MAPK11 in the cell response to ionizing radiation (IR). Materials and methods: We developed MAPK11/14 knockdown through shRNA and CRISPR interference gene perturbation approaches and analysed the downstream effects on cell responses to ionizing radiation in A549, HCT-116 and MCF-7 cancer cell lines. Specifically, we assessed IR toxicity by clonogenic assays; DNA damage response activity by immunocytochemistry; apoptosis and cell cycle by flow cytometry (Annexin V and propidium iodide, respectively); DNA repair by comet assay; and senescence induction by both X-Gal staining and gene expression of senescence-associated genes by RT-qPCR. Results: Our findings demonstrate a critical role of MAPK11 in the cellular response to IR by controlling the associated senescent phenotype, and without observable effects on DNA damage response, apoptosis, cell cycle or DNA damage repair. Conclusion: Our results highlight MAPK11 as a novel mediator of the cellular response to ionizing radiation through the control exerted onto IR-associated senescence.

Duct-like Recess in the Infundibular Portion of Third Ventricle Craniopharyngiomas: An MRI Sign Identifying the Papillary Type.

BACKGROUND AND PURPOSE: Papillary craniopharyngiomas (PCPs) are particularly challenging lesions requiring accurate diagnosis to plan the best therapy. Our aim was to define a narrow duct-like recess identified on MR imaging at the base of papillary craniopharyngiomas with a strict third ventricle location. MATERIALS AND METHODS: A duct-like recess at the infundibular portion of craniopharyngiomas was observed on conventional T1WI and T2WI in 3 strict third ventricle papillary craniopharyngiomas in our craniopharyngioma series (n = 125). We systematically investigated this finding on the MR imaging of 2582 craniopharyngiomas and 10 other categories of third ventricle tumors (n = 690) published in the modern era (1986-2020). The diagnostic value and significance of this finding are addressed. RESULTS: The duct-like recess was recognized in 52 papillary craniopharyngiomas, including 3 of our own cases, as a narrow canal-shaped cavity invaginated at the tumor undersurface, just behind the optic chiasm. This structure largely involves papillary craniopharyngiomas with a strict third ventricle topography (96%), follows the same diagonal trajectory as the pituitary stalk, and finishes at a closed end. The duct-like recess sign identifies the papillary craniopharyngioma type with a specificity of 100% and a sensitivity of 38% in the overall craniopharyngioma population. This finding can also establish the strictly intra-third ventricle location of the lesion with a 90% specificity and 33% sensitivity. These recesses appear as hypointense circular spots on axial/coronal T1WI and T2WI. Their content apparently corresponds to CSF freely flowing within the suprasellar cistern. CONCLUSIONS: The presence of a duct-like recess at the infundibular portion of a third ventricle tumor represents a distinctive hallmark of papillary craniopharyngiomas that can be used as a simple MR imaging sign to reliably diagnose these lesions.

Expiration Date Effect on Mechanical and Chemical Properties of Glass Ionomer Cements

ABSTRACT: The glass ionomer cements (GICs) is a generic name given to a group of materials widely used in clinical dentistry which if used after the specified expiration date, material properties may be affected. to evaluate the Vick ers microhardness, surface morphology and the energy dispersive X-ray microanalysis (EDX), of GICs with different expiration dates that were stored at room temperature. specimens of highly viscous glass ionomer cement (HVGIC) (Ketac Cem and Ketac Molar) and resin-modified glass ionomer cement (RMGIC) (Vitrebond) with different expiration dates (current, close to their expiration and expired) were prepared for Vickers microhardness test and scanning electronic microscopy (SEM) with EDX, measuring 5 mm in diameter and 2 mm length, per the manufacturer's instructions, in standard cylindrical teflon molds. For the comparison of obtained values, the ANOVA test was used, while Tukey test was used for the multiple comparisons. In all the GICs used, the microhardness decreased as the expiration date approached, finding a significant statistical differen ce (P<0.05) in Ketac Molar and Vitrebond. SEM sample analysis revealed similar cohesive cracks in all tested materials. The EDX analysis revealed the presence of the elements F, Al and Si in all GICs and Ca only in Ketac Molar and Ketac Cem. The elements were found in a higher atomic percentage in the GICs with an current date and in a lower percentage in those with an expired date. HVGIC and RMGIC with an expiration date finish and that were stored at room temperature, suffer significant physical and chemical changes, which could put doubts its clinical effectiveness.

RESUMEN: El cemento de ionómero de vidrio (CIV) es un nombre genérico que se le da a un grupo de materiales ampliamente utilizados en odontología clínica que si se usan después de la fecha de vencimiento especificada, las propiedades del material pueden verse afectadas. evaluar la microdureza Vickers, la morfología superficial y el microanálisis de energía dispersa de rayos X (EDX), de CIV con diferentes fechas de caducidad almacenados a temperatura ambiente. Muestras de cemento de ionómero de vidrio de alta viscosidad (CIVAV) (Ketac Cem y Ketac Molar) y cemento de ionómero de vidrio modificado con resina (CIVMR) (Vitrebond) con diferentes fechas de vencimiento (vigente, próximo a su vencimiento y vencido) de 5 x 2 mm, fueron preparadas para microscopía electrónica de barrido (MEB) con EDX y microdureza Vickers, según las instrucciones del fabricante, en moldes de teflón cilíndricos estándar. Para la comparación de los valores obtenidos se utilizó la prueba ANOVA, mientras que para las comparaciones múltiples se utilizó la prueba de Tukey. En todos los CIV utilizados, la microdureza disminuyó a medida que se acercaba la fecha de vencimiento, encontrándose una diferencia estadística significativa (P <0.05) en Ketac Molar y Vitrebond. El análisis de la muestra en MEB reveló grietas cohesivas similares en todos los materiales probados. El análisis EDX reveló la presencia de los elementos F, Al y Si en todos los GIC y Ca solo en Ketac Molar y Ketac Cem. Los elementos se encontraron en mayor porcentaje atómico en los GIC con fecha vigente y en menor porcentaje en aquellos con una fecha vencida. Los CIVAV y CIVMR con fecha de caducidad vencida y que fueron alma- cenados a temperatura ambiente, sufrieron cambios físicos y químicos importantes, lo que podría poner en duda su efectividad clínica.

Characterization of inflammatory bowel disease in Colombia: Results of a national register. / Caracterización de la enfermedad inflamatoria intestinal en Colombia: resultados de un registro nacional.

AIM: To determine the clinical, sociodemographic, and treatment characteristics of inflammatory bowel disease (IBD) in a Colombian population register. METHODS: A descriptive, analytic, observational, cross-sectional, multicenter study on patients with IBD from 17 hospital centers in 9 Colombian cities was conducted. RESULTS: A total of 2,291 patients with IBD were documented, 1,813 (79.1%) of whom presented with ulcerative colitis (UC), 456 (19.9%) with Crohn's disease (CD), and 22 with IBD unclassified (0.9%). The UC/CD ratio was 3.9:1. A total of 18.5% of the patients with UC and 47.3% with CD received biologic therapy. Patients with extensive UC had greater biologic therapy use (OR = 2.78, 95% CI: 2.10-3.65, p = 0.000), a higher surgery rate (OR = 5.4, 95% CI: 3.5-8.3, p = 0.000), and greater frequency of hospitalization (OR = 4.34, 95% CI: 3.47-5.44, p = 0.000). Patients with severe UC had greater biologic therapy use (OR = 5.04, 95% CI: 3.75-6.78, p = 0.000), a higher surgery rate (OR = 8.64, 95% CI: 5.4-13.78, p = 0.000), and greater frequency of hospitalization (OR = 28.45, 95% CI: 19.9-40.7, p = 0.000). CD patients with inflammatory disease behavior (B1) presented with a lower frequency of hospitalization (OR = 0.12, 95% CI: 0.07-0.19, p = 0.000), a lower surgery rate (OR = 0.08, 95% CI: 0.043-0.15, p = 0.000), and less biologic therapy use (OR = 0.26, 95% CI: 0.17-0.41, p = 0.000). CONCLUSION: In Colombia, there is a predominance of UC over CD (3.9:1), as occurs in other Latin American countries. Patients with extensive UC, severe UC, or CD with noninflammatory disease behavior (B2, B3) have a worse prognosis.

p38ß (MAPK11) mediates gemcitabine-associated radiosensitivity in sarcoma experimental models.

BACKGROUND AND PURPOSE: Gemcitabine is an antitumour agent currently used in the treatment of several types of cancer with known properties as a radiosensitizer. p38MAPK signalling pathway has been shown to be a major determinant in the cellular response to gemcitabine in different experimental models. However, the molecular mechanism implicated in gemcitabine-associated radiosensitivity remains unknown. MATERIALS AND METHODS: The human sarcoma cell lines A673 and HT1080, and a mouse cell line derived from a 3-methylcholanthrene induced sarcoma were used as experimental models. Modulation of p38MAPKs was performed by pharmacological approaches (SB203580) and genetic interference using lentiviral vectors coding for specific shRNAs. Viability was assessed by MTT. Gene expression was evaluated by western blot and RT-qPCR. Induction of apoptosis was monitored by caspase 3/7 activity. Response to ionizing radiation was evaluated by clonogenic assays. RESULTS: Our data demonstrate that chemical inhibition of p38MAPK signalling pathway blocks gemcitabine radiosensitizing potential. Genetic interference of MAPK14 (p38α), the most abundantly expressed and best characterized p38MAPK, despite promoting resistance to gemcitabine, it does not affect its radiosensitizing potential. Interestingly, specific knockdown of MAPK11 (p38ß) induces a total loss of the radiosensitivity associated to gemcitabine, as well as a marked increase in the resistance to the drug. CONCLUSION: The present work identifies p38ß as a major determinant of the radiosensitizing potential of gemcitabine without implication of p38α, suggesting that p38ß status should be analysed in those cases in which gemcitabine is combined with ionizing radiation.

P53 pathway is a major determinant in the radiosensitizing effect of Palbociclib: Implication in cancer therapy.

Targeting cell cycle has become one of the major challenges in cancer therapy, being Palbociclib, a CDK4/6 inhibitor, an excellent example. Recently, it has been reported that Palbociclib could be a novel radiosensitizer agent. In an attempt to clarify the molecular basis of this effect we have used cell lines from colorectal (HT29, HCT116) lung (A549, H1299) and breast cancer (MCF-7). Our results indicate that the presence of a p53 wild type is strictly required for Palbociclib to exert its radiosensitizing effect, independently of the inhibitory effect exerted on CDK4/6. In fact, abrogation of p53 in cells with functional p53 blocks the radiosensitizing effect of Palbociclib. Moreover, no radiosensitizing effect is observed in cells with non-functional p53, but restoration of p53 function promotes radiosensitivity associated to Palbociclib. Furthermore, the presence of Palbociclib blocks the transcriptional activity of p53 in an ATM-dependent-fashion after ionizing radiation exposure, as the blockage of p21/WAF1 expression demonstrates. These observations are a proof of concept for a more selective therapy, based on the combination of CDK4/6 inhibition and radiotherapy, which would only benefit to those patients with a functional p53 pathway.

Blockage of autophagic flux is associated with lymphocytosis and higher percentage of tumoral cells in chronic lymphocytic leukemia of B cells.

PURPOSE: Autophagy has lately emerged as an important biological process with implications in several hematological pathologies. Recently, a growing body of evidence supports a putative role of autophagy in chronic lymphocytic leukemia; however, no definitive clue has been established so far. To elucidate this issue, we have developed a pilot study to measure autophagic flux in peripheral blood mononuclear cells from chronic lymphocytic leukemia patients, and explored its correlation with classical clinical/analytical parameters. METHODS/PATIENTS: Thirty-three chronic lymphocytic leukemia patients participated in the study. Autophagic flux in peripheral blood mononuclear cells was determined by western blot measuring the levels of the proteins p62 and lipidated LC3. Moreover, p62 mRNA levels were analyzed by RT-qPCR. RESULTS: Lymphocytosis and the percentage of tumoral lymphocytes in chronic lymphocytic leukemia patients statistically correlate with a blocked autophagic flux. CONCLUSION: Alterations in autophagic flux could play an important role in the physiopathology of chronic lymphocytic leukemia.

[Knowledge and preferences on end-of-life resources in a sample of professionals of the Community of Madrid]. / Conocimientos y preferencias sobre los recursos existentes al final de la vida en una muestra de la Comunidad de Madrid.

OBJECTIVE: The Law (4/2017) on rights and guarantees of persons in the process of dying in Community of Madrid regulates the exercise of the rights of the person during this process. The main objective of this study was to determine the knowledge and preferences about palliative sedation (PS), euthanasia, physician-assisted suicide (PAS), and adequacy of the therapeutic effort (ATE). MATERIALS AND METHODS: A questionnaire was designed to collect knowledge about definition and legality of detailed resources, and disposition for themselves or for a relative. The questionnaire was completed by a total of 192 palliative care Conference attendees (October 2017). RESULTS: Of those that completed the questionnaire, 160 (83.3%) were women, and the mean age was of 39 years (SD=15.8). More than two-thirds (131; 68.2%) did not know that the law existed. The definition with the highest rate of knowledge was on PS (89.1%; 171) and the lowest was ATE (50.5%; 97). On legality, the most successful was euthanasia (94.8%; 182) and the lowest was ATE (63.5%; 122). PS was considered the most appropriate resource (93.2%; 179), and the greater willingness of use in both relatives (91.7%; 176) as well as by themselves (90.6%; 174). PAS was the least suitable (34.4%; 66), and that less might resort in case of end-of-life of a relative (29.7%; 57), and themselves (33.3%; 64). CONCLUSIONS: There is a greater awareness of the condition of legality or illegality of each resource than of the definition of the terms. The use of the PAS and euthanasia is disapproved. It is important to clarify the meaning of ATE, and clarify its confusion with other measures such as PS and PAS.

Topographic Diagnosis of Craniopharyngiomas: The Accuracy of MRI Findings Observed on Conventional T1 and T2 Images.

BACKGROUND AND PURPOSE: The topography of craniopharyngiomas has proved fundamental in predicting the involvement of vital brain structures and the possibility of achieving a safe radical resection. Beyond the imprecise term "suprasellar," indiscriminately used for craniopharyngiomas, an accurate definition of craniopharyngioma topography should be assessed by preoperative MR imaging. The objective of this study was to investigate the MRI findings that help define craniopharyngioma topography. MATERIALS AND METHODS: This study retrospectively investigated a cohort of 200 surgically treated craniopharyngiomas with their corresponding preoperative midsagittal and coronal conventional T1- and T2-weighted MR images, along with detailed descriptions of the surgical findings. Radiologic variables related to the occupation of the tumor of intracranial compartments and the distortions of anatomic structures along the sella turcica-third ventricle axis were analyzed and correlated with the definitive craniopharyngioma topography observed during the surgical procedures. A predictive model for craniopharyngioma topography was generated by multivariate analysis. RESULTS: Five major craniopharyngioma topographies can be defined according to the degree of hypothalamic distortion caused by the tumor: sellar-suprasellar, pseudointraventricular, secondary intraventricular, not strictly intraventricular, and strictly intraventricular. Seven key radiologic variables identified on preoperative MRI allowed a correct overall prediction of craniopharyngioma topography in 86% of cases: 1) third ventricle occupation, 2) pituitary stalk distortion, 3) relative level of the hypothalamus in relation to the tumor, 4) chiasmatic cistern occupation, 5) mammillary body angle, 6) type of chiasm distortion, and 7) tumor shape. CONCLUSIONS: Systematic assessment of these 7 variables on conventional preoperative T1 and T2 MRI is a useful and reliable method to ascertain individual craniopharyngioma topography.

The first sixty-five craniopharyngioma operations in France.

Craniopharyngiomas (CPs) are benign epithelial tumors that develop along the hypothalamus-hypophyseal axis and were first described by Jakob Erdheim in 1904. These tumors have represented a challenge for surgeons since the rise of modern neurosurgery. The study of CPs is linked to the development of this surgical discipline in parallel with neuroendocrinology within the French school of neurology, led by Joseph Babinski. For the present study, all CP cases published in the French scientific literature before the development of modern neuroradiology were gathered, and 65 cases that underwent surgical procedures between 1921 and 1973 were selected. From our analysis of them, useful information has been obtained that can be applied to the management of CPs today. Most tumors were adamantinomatous CPs (62 patients) with an infundibulo-tuberal location (40.6%). The most frequent surgical route employed was subfrontal (69%). Selection of the surgical approach and degree of removal did not appear to have been influenced by the presumed topography of the tumor, and resulted in a poor outcome in 47% of patients. However, the authors were able to recognize the presence of symptoms indicating that the tumor had caused hypothalamic and/or infundibular damage, such as seen in the infundibulo-tuberal syndrome, first described by Claude and Lhermitte in 1917. At present, the optimal surgical approach and degree of removal are still the subject of debate, although the presence of clinical signs pointing to hypothalamic involvement by CPs should always be preoperatively accurately assessed to improve surgical outcomes.

CHK1 expression in Gastric Cancer is modulated by p53 and RB1/E2F1: implications in chemo/radiotherapy response.

Radiation has a limited but relevant role in the adjuvant therapy of gastric cancer (GC) patients. Since Chk1 plays a critical function in cellular response to genotoxic agents, we aimed to analyze the role of Chk1 in GC as a biomarker for radiotherapy resistance. We analyzed Chk1 expression in AGS and MKN45 human GC cell lines by RT-QPCR and WB and in a small cohort of human patient's samples. We demonstrated that Chk1 overexpression specifically increases resistance to radiation in GC cells. Accordingly, abrogation of Chk1 activity with UCN-01 and its expression with shChk1 increased sensitivity to bleomycin and radiation. Furthermore, when we assessed Chk1 expression in human samples, we found a correlation between nuclear Chk1 accumulation and a decrease in progression free survival. Moreover, using a luciferase assay we found that Chk1's expression is controlled by p53 and RB/E2F1 at the transcriptional level. Additionally, we present preliminary data suggesting a posttranscriptional regulation mechanism, involving miR-195 and miR-503, which are inversely correlated with expression of Chk1 in radioresistant cells. In conclusion, Chk1/microRNA axis is involved in resistance to radiation in GC, and suggests Chk1 as a potential tool for optimal stratification of patients susceptible to receive adjuvant radiotherapy after surgery.

Espondiloartritis anquilosante: revisión de hallazgos imagenológicos en la columna / Ankylosing spondyloarthritis: review of spinal imaging findings

Abstract: Introduction. Ankylosing spondyloarthritis (AS) is the most common and representative of seronegative spondyloarthropathy. It is characterised by chronic inflammation of the axial skeleton, leading to chronic back pain and progressive stiffness. It typically occurs in young patients, with symptoms often appearing with peak onset between 20 and 30 years of age, and is strongly associated with human leukocyte antigen B-27 (HLA B-27). Current imaging techniques are central in the management of these patients. The recognition of its classic imaging findings and its complications is essential for radiologists. Objectives. To present a pictorial review of the spinal imaging findings in patients with AS. Methods and materials. An analysis will be made of the spinal imaging findings in conventional radiography, CT and MRI in multiple patients from our medical centre. The most representative findings, complications, differential diagnoses, and some radiological key points will be shown.

Resumen: Introducción. La espondilitis anquilosante (EA) es la artropatía seronegativa más común y representativa. Se caracteriza por inflamación crónica del esqueleto axial, dolor referido a la columna vertebral de tipo inflamatorio y rigidez progresiva. Típicamente se manifiesta en pacientes jóvenes que inician su sintomatología entre los 20-30 años de edad y está ligada al antígeno leucocitario humano B-27 (HLA B-27). Las imágenes son fundamentales en el manejo de estos pacientes. Es deber del radiólogo reconocer los hallazgos imagenológicos presentes. Objetivos. Realizar una revisión pictográfica de hallazgos imagenológicos presentes en la columna vertebral de pacientes portadores de EA. Material y método. Análisis de las manifestaciones imagenológicas de columna más representativas de la EA en pacientes de nuestro centro en radiografía convencional, TC y RM, junto con posibles complicaciones y diagnósticos diferenciales.

Extravasación de medios de contraste intravenosos: lo que todo radiólogo debe saber / Extravasation of intravenous contrast media: what every radiologist should know

The accidental release of intravenous contrast media (ICM) from the intravascular compartment to the adjacent soft tissues is one of the most frequent complications of the injection procedure in multi-slice CT (MSCT). Its incidence is low, occurring in between 0.1 and 0.9 percent of patients undergoing these studies. Affected areas usually present mild lesions characterized by swelling and local erythema and that tend to resolve spontaneously without sequelae. However, serious lesions may also occur, such as compartment syndrome. For these reasons it is essential to know patients at risk, precautionary measures, specific technical factors, early diagnosis and appropriate management of this complication. These elements constitute basic skills that every radiologist must possess.

La salida accidental de medio de contraste intravenoso (MCI) desde el compartimento intravascular hacia los tejidos de partes blandas adyacentes es una de las complicaciones más frecuentes del procedimiento de inyección en tomografía computada multicorte (TCMC). Su incidencia es baja, ocurre entre el 0,1 y el 0,9 porciento de los pacientes que se someten a estos estudios. Las zonas afectadas generalmente presentan lesiones leves caracterizadas por aumento de volumen y eritema local que tienden a remitir espontáneamente sin secuelas. Sin embargo, también pueden ocurrir lesiones graves, como un síndrome compartimental. Por estas razones es fundamental conocer los pacientes en riesgo, las medidas de precaución, los factores técnicos específicos, el diagnóstico precoz y el manejo oportuno de esta complicación. Estos elementos constituyen competencias básicas que todo radiólogo debe poseer.

A comparison of two enzyme immunoassay tests for the detection of IgG antibodies for measles virus.

BACKGROUND: Despite the reduction in the incidence of measles in recent years, outbreaks have appeared in various countries in Central and Western Europe. Estimating the percentage of immune individuals is fundamental for establishing control strategies in these situations. METHODS: A total of 1,147 serum samples from healthy volunteers were tested by two commercial enzyme immunoassay (EIA) tests that detect antibodies for the measles virus: Enzygnost Anti-Measles Virus/IgG (Siemens, Marburg, Germany) and VIDAS Measles IgG (bioMerieux, Inc.). The following values were calculated for each test: sensitivity, specificity, positive and negative predictive values, and likelihood ratios. RESULTS: Compared to the Enzygnost test, the sensitivity of the VIDAS test was 98.0% and the specificity was 78.1%. The likelihood ratio (LR) values were + 4.48, - 0.025 and +/- 0.17. CONCLUSIONS: The VIDAS Measles IgG test is a quick method with good sensitivity for detecting IgG antibodies for the measles virus compared to the Enzygnost EIA test.

Relevance of intracranial hypertension control in the management of Cryptococcus neoformans meningitis related to AIDS.

PURPOSE: To evaluate the relationship between intracranial hyperpressure (HICP) and mortality in patients with cryptococcal meningitis related to AIDS (CMRA). METHODS: This was an observational retrospective study. Patients were treated according to the Infectious Diseases Society of America recommendations during the evaluation period (days 0, 3, 5 and after hospitalization). High intracranial pressure (HICP) was defined as ICP values of C250 mm H20. The correlation between HICP and mortality at each of the three time points considered was investigated. Statistical analysis on the descriptive parameters and on the probability of a "death" event (odds ratio, OR) at each of those three time points was performed using the statistical software program Epidata. RESULTS: Eighty patients were included in this study, of whom 53 (66.25 %) were male. The average age of the patients was 37.5 ± 8.1 (range 22­55) years. The median CD4?lymphocyte cell count was 35 (range 0­367) cells/ml. Among the entire patient cohort, 53 patients had a favorable outcome, and the mortality rate was 33.75 %. At baseline (day 0), 57 subjects (71.5 %) presented HICP, and these patients had a higher mortality rate than those with a normal ICP, but the difference did not reach statistical significance[OR 1.65, 95 % confidence interval (CI) 0.56­4.84]. On day 3, 41 of the patients presented HICP, and HICP at this timepoint was significantly associated with an increased risk of mortality (OR 4.35, 95 % CI 1.56­12.09). On day 5, 35(43.5 %) patients presented HICP, and HCIP at this time point was also significantly associated with higher mortality (OR 7.23, 95 % CI 2.53­20.14). CONCLUSION: The results of this study confirm an association between HICP and mortality in patients with CMRA and indicate that the control of ICP during the first 5 days of hospitalization is more important than managing HICP only at baseline.

Fluorescence in situ hybridization analysis of CCND3 gene as marker of progression in bladder carcinoma.

The aim of this study was to assess patterns of CCND3 gene amplification in bladder cancer and correlate gene status with recurrence-free and progression-free survival. A sequential cohort series of 102 primary bladder tumor samples in which there was enough tissue material to assess CCND3 gene status by fluorescent in situ hybridization (FISH) was the study group. CCND3 gene FISH amplification present in 31.4 percent of bladder carcinomas, was related to tumor progression (p=0.021) and lower time to progression (mean+-SD; 25.75+-15.25 months) as compared to 33.29+-11.0 months in the CCND3 not amplified group (p=0.05). By immunohistochemistry, Cyclin D3 labeling index was higher in the CCND3 amplified group (mean+-SD, 76.69+-27.51) than in not amplified (mean+-SD, 21.57+-7.02) (p less than 0.0001). The univariate survival analysis showed CCND3 gene amplification to be associated to a shorter progression-free survival (p=0.020) together with WHO histological grade (p=0.001) and pT stage category (p less than 0.0001). Cox’s regression analysis selected CCND3 amplification as an independent predictor of progression-free survival (p= 0.030, RR3.561, 95 percent CI 1.128-11.236) together with pT category (p less than 0.0001, RR5.834, 95 percent CI 2.364-14.395). Our FISH analysis suggests that CCND3 gene amplification is a marker of aggressiveness and might be a predictor of tumor progression in bladder urothelial carcinoma.