The CAPRA-S Score and Immune Dysfunction as a Guide to Outcome in Men Treated with Prostatectomy Radical as Mono-Therapy for Prostate Cancer

Objective: Incorporate the immune function as determined by the absolute lymphocyte count (ALC) into the CAPRA-S risk stratification score to determine if predictive values could be improved. Materials and Methods: The clinical pathological findings in the surgical specimen and total PSA were used to define the three CAPRA-S risk groups. One month after surgery and at each follow up total PSA and the ALC were determined, until biochemical failure (BF) or the end of the study period. A cut off value of <1,000 lymphocytes/mm3 was used to define lymphocytopenia (LCP). Each CAPRA-S group was sub-divided based on the presence or absence of LCP. Kaplan-Meier biochemical failure free survival (BFFS) curves and restricted mean biochemical failure free survival times were calculated for each group. Results: 404 patients participated of whom 103 (25.5%) underwent BF. 270 men were CAPRA-S low risk (LR), 89 intermediate risk (IR) and 45 high risk (HR), of whom LCP was found in 22 (8%) of low risk, 24 (27%) of intermediate risk and 17 (38%) of high risk men. LCP was significantly associated with a higher PSA, higher Gleason and CAPRA-S scores and BF. HRs were 1.76 for IR, 2.49 for HR and 1.29 for LCP. Five-year BFFS for men without LCP, LR 93.5%, IR 61% and HR 36%, for those with LCP, LR 55%, IR 25% and HR 6%. All patients with LCP and IR or HR scores relapsed within 6 years. 10 year BFFS for men without LCP were 71% LR, 43% IR and 23% HR, LR with LCP 16%. Men with BF had increasing LCP approximately 18 months before BF. Conclusions: The incorporation of the ALC taken one month after surgery with the CAPRA-S improves risk stratification; decreases in the ALC suggest that BF is occuring. These results need to be confirmed with larger studies (AU)

Objetivo: Establecer el riesgo de recidiva bioquímica(RBQ) basado en la puntuación CAPRA-S (riesgo bajo(RB) , riesgo intermedio (RI) y riesgo alto (RA) y recuentoabsoluto de linfocitos (RAL) ≤1000 por mm3(definidiacomo linfocitipenia LCP).Material y Métodos: Entre 2005 y 2020, se realizaun estudio observacional prospectivo de sujetos con cáncerpróstatico tratado con cirugia. Se registran los hallazgos delespécimen quirúrgico y el PSA para definir la CAPRA-S.Un mes pos-cirugía y durante el seguimiento el PSA y RALfueron determinados hasta la RBQ o final del estudio. Seconstruye un modelo de supervivencia flexible paramétrico(FP) para predecir la RBQ a 5 años utilizando la puntuaciónCAPRA-S y la LCP. Se evalúan mediante regresión localponderada mediciones repetidas de los RAL y el tiempo aRBQ o fin del estudio.Resultados: De los 404 participantes observaron 103(25,5%) RBQ. Puntajes de la CAPRA-S: 270 RB, 89 RI y45 RA. La LCP estaba asociada con niveles elevados delPSA, puntuación Gleason, márgenes comprometidos, extensión extracapsular, invasión de vesículas seminales ynodos linfáticos. El modelo FP incorporo en forma independiente y significativa ( coeficiente con valor P<0,01) laLCP ( 1,29), RA (2,49), RI (1,76) y RB (1); mostrando unaC de Harrell de 0,81 con adecuada validez. la media restringida en años (MR) para ocurrencia de RBQ, como lasupervivencia predicha (SP) a 5 años fueron: sin LCP RA(MR: 3,63; SP 42,1%) RI (MR 4,3; SP 63,1%) RB (MR4,83; SP 91,7%) con LCP RA (MR 2,1; SP 4,34%) RI (MR3,14; SP 18,9%) y RB (MR 4,42; SP 73,1%). Los sujetoscon RBQ tuvieron LCP 18 meses previo a la RBQ. LCP más CAPRA-S predicen la RB en sujetos tratado con cirugia (AU)

Análisis del rol de los exámenes de imagen en el régimen de garantías explícitas en salud en Chile / Analysis of the role of imaging exams in the regime of explicit health guarantees in Chile

Resumen: Objetivo: Describir la participación de los exámenes de imagen en el Régimen de Garantías Explícitas en Salud en Chile y analizar el papel de los radiólogos en este campo. Materiales y métodos: todas las patologías incluidas en el Programa de garantías explícitas en salud, cuentan con una guía de práctica clínica (GC) y un listado de prestaciones específicas (LP). Ambos fueron analizados respecto a la cantidad y la modalidad de los exámenes de imagen recomendados, la presencia de radiólogos dentro de los paneles de expertos y la concordancia entre las recomendaciones de las guías y los Listados de Prestaciones. Resultados: 60 GC (67%) y 55 LP (69%) incluyen pruebas de imagen dentro de sus prestaciones garantizadas. 7 GC (8%) recomiendan pruebas de imágenes no cubiertas en su listado de prestaciones respectivos y 5 pruebas de imágenes del LP (6%) no están incluídas en las guías clínicas. La participación de un radiólogo en el panel de expertos se asoció con la ausencia de discrepancias en las pruebas de imagen entre GC y LP (p = 0,007). Discusión: el diagnóstico por imágenes juega un papel importante dentro del Programa de garantías explícitas y se asocia al aumento de los costos de atención médica. Algunos casos de discordancia entre las guías clínicas y los Listados de Prestaciones representan costos económicos y sociales significativos que podrían reducirse al incluir radiólogos en los paneles de expertos, así como optimizar el uso de recursos y reducir la exposición de los pacientes a la radiación ionizante.

Abstract: Objective: To describe the involvement diagnostic imaging exams in the framework of Regime of Explicit Health Guarantees in Chile and analyze the role of radiologists in this field. Materials and methods: Every pathology included in the Explicit Healthcare Guarantees Program encompasses an expert consensus clinical guideline (CG) and a specific services list (SL). Both of them were analyzed regarding the amount and modality of imaging exams recommended, the presence of radiologists within the expert panels and the concordance between guidelines recommendations and service lists. Results: 60 CG (67%) and 55 SL (69%) include imaging tests within their guaranteed services. Seven CG (8%) recommend medical imaging tests not covered in their respective services list and 5 SL (6%) reference imaging tests not included in the clinical guidelines. The involvement of a radiologist on the expert panel was associated with the absence of imaging test discrepancies between CG and SL (p=0.007). Discussion: Diagnostic imaging plays an important role within the Explicit Healthcare Guarantees Program and is associated with rising healthcare costs. There are cases of discordance between clinical guidelines and specific services lists that account for significant economic and social costs, which may be reduced by including radiologists on expert panels, optimizing resource use and lowering patients' exposure to ionizing radiation.

Psychoeducational intervention to improve oral assessment in people with autism spectrum disorder, BIO-BIO region, Chile.

BACKGROUND: To assess the effectiveness of a psychoeducational intervention program designed to facilitate the performance of a series of steps of oral examination in children, adolescents and adults with autism spectrum disorder (ASD), in the Bio-Bio region, Chile. MATERIAL AND METHODS: A prospective, quasi-experimental study with pre-intervention, post-intervention and maintenance tests was carried out. Behavior was measured using Frankl's scale and the number of steps of a dental examination completed (1-10 steps) was also recorded. Only 104 of the 188 subjects with ASD that agreed to participate in the study met all the inclusion criteria. RESULTS: 82 people with ASD completed the psychoeducational intervention. The mean number of steps achieved pre- and post-intervention was 4.1 and 9.4, resulting in a clinically and statistically significant difference. Regarding behavior, the median in the pre-test was 2 (negative behavior) and in the post-test it increased to 3 (positive behavior), this difference being relevant and statistically significant. A maintenance test one month later on 63 people with ASD found no variations in behavior and in the number of examination steps completed. CONCLUSIONS: The proposed intervention was effective as an increase of more than 5 in the number of steps of examination completed was achieved. Frankl's behavior rating also increased, from negative to positive, in a group of children, adolescents and adults with ASD.

Anti TNF como inductor de lupus cutáneo: caso clínico / Anti TNF as inducer of cutaneous lupus: clinical case

El mayor acceso a las terapias biológicas para el tratamiento de múltiples enfer-medades autoinmune trae consigo el mayor riesgo de padecer eventos adversos relacionados al uso de estos2,4. Presentamos un caso clínico de una paciente con diagnóstico de artritis reumatoide en tratamiento con ANTI TNF

The greater access to biological therapies for the treatment of multiple autoim-mune diseases brings with it the greatest risk of suffering adverse events related to the use of these (2,4). We present a clinical case of a patient diagnosed with rheumatoid arthritis in treatment with ANTI TNF

Vo2 máximo indirecto y edad fitness de sedentarios y no sedentarios / Vo2 indirect maximum and fitness age of sedentary and non-sedentary

El objetivo es: comparar la edad cronológica con la edad fitness obtenida por medio del VO2 máximo indirecto, de un grupo de personas sedentarias y no sedentarias. Método: 253 personas fueron evaluadas respecto a masa corporal, estatura, perímetro de cintura, frecuencia cardiaca basal y un cuestionario del modelo web "Fitness Calculator". Los resultados demostraron diferencias significativas en las variables antropométricas y fisiológicas entre personas sedentarias y no sedentarias (P<,001). Las personas no sedentarias tienen un mayor VO2máx en comparación con las personas sedentarias. Las personas sedentarias indican que presentan una edad fitness que se encuentra sobre 12 años cronológicos promedio de lo esperado. Conclusión: Las personas sedentarias tienen una mayor edad fitness, esto permite establecer que su cuerpo se deteriora más rápido que los no sedentarios. El bajo VO2 máx es un potente predictor de la capacidad cardiorrespiratoria y se establece como un predictor de enfermedades cardiovasculares

The purpose was to compare chronological age with fitness age obtained through indirect VO2max in a group of sedentary and non-sedentary people. Method: 253 people were evaluated for body mass, height, waist circumference, basal heart rate and a web model questionnaire "Fitness Calculator". The results: showed significant differences in anthropometric and physiological variables between sedentary and non-sedentary people (P <.001). Non-Sedentary people have a greater higher VO2máx group compared to sedentary people. This indicates that sedentary people have a fitness age 12 years over their expected chronological average age. Conclusion: Sedentary people have a higher fitness age; therefore your body deteriorates faster than the non-sedentary people. A low level of VO2máx is a powerful predictor of cardiorespiratory capacity and of cardiovascular diseases

The effect of Lactobacillus acidophilus and Lactobacillus casei on the in vitro bioaccessibility of flaxseed lignans (Linum usitatissimum L.).

Secoisolariciresinol (SECO) is present in flaxseeds as a glucoside, secoisolariciresinol diglucoside (SDG), which can be metabolized to enterodiol (ED) and enterolactone (EL) by the human intestinal microbiota. The aim of this study was to evaluate the effect of Lactobacillus casei and Lactobacillus acidophilus on the bioaccessibility of flaxseed lignans from a complete in vitro digestion of whole flaxseeds (WFs) and flaxseed flour (FF). Lignans are only detected in the large intestine. The bioaccessibility of SDG for FF digestion can be ordered as follows: control (without probiotics) > L. casei > L. acidophilus; and for WF digestion, only in the presence of L. casei SDG was detected. For SECO and EL, the presence of both probiotics had no effect on FF and WF digestion. However, in the digestion of WF both L. casei and L. acidophilus increased ED bioaccessibility in the first 12 h; but both probiotics had no significant effect on FF digestion.

Comparación de 3 nomogramas en línea con la detección de las células primarias circulantes de la próstata para predecir el cáncer de próstata en la biopsia inicial / A comparison of 3 on-line nomograms with the detection of primary circulating prostate cells to predict prostate cancer at initial biopsy

Introducción: Los nomogramas que incluyen el PSA para predecir los resultados de una biopsia prostática son de utilidad en la clínica diaria. En este estudio de hombres con sospecha de cáncer prostático comparamos el uso de 3 nomogramas online con la detección de células prostáticas circulantes (CPC) para predecir los resultados de la biopsia prostática. Métodos y pacientes: Una serie de varones con sospecha de cáncer fueron sometidos a una biopsia prostática de 12 muestras. Se registraron la edad, APE total, porcentaje de APE libre, historia familiar de cáncer prostático, origen étnico y resultados de una ecografía transrectal. Se calculó el riesgo de cáncer prostático utilizando 3 nomogramas. Se separaron las células mononucleares por centrifugación diferencial de 8 ml sangre venosa e identificaron las CPC utilizando inmunocitoquímica con anti-APE y anti-P504S. Una CPC fue definida como una célula expresando APE y P504S y el test como positiva/negativa. La biopsia fue clasificada como cáncer/no-cáncer. Por cada parámetro el área bajo la curva fue calculada y los rendimientos diagnósticos comparados. Resultados: Un total de 1.223 hombres>55 años participaron, 467 (38,2%) tuvieron una biopsia positiva para cáncer, de los cuales 114/467 (24,4%) tuvieron un cáncer no-significativo. El análisis del área bajo la curva mostró que la detección de las CPC fue superior (p<0,001), evitando el 57% de las biopsias prostáticas, mientras que no detectó el 4% de los cánceres significativos. Conclusiones: La detección de CPC fue superior a los otros modelos para predecir los resultados de la biopsia prostática inicial, reduce potencialmente el número de biopsias innecesarias y no detecta solo una pequeña fracción de los pacientes con cáncer clínicamente significativos. Fue superior a los otros modelos en este aspecto, cuando considerados negativos los nomogramas no detectaron un número significativo de cánceres agresivos. De ser un test positivo/negativo, la detección de CPC evita la definición de un punto de corte, lo cual podría variar entre poblaciones diferentes

Introduction: The use of nomograms which include the PSA may improve the predictive power of obtaining a prostate biopsy (PB) positive for cancer. We compare the use of three on-line nomagrams with the detection of primary malignant circulating prostate cells (CPCs) to predict the results of an initial PB in men with suspicion of prostate cancer. Methods and patients: Consecutive men with suspicion of prostate cancer underwent a 12 core TRUS prostate biopsy; age, total serum PSA, percent free PSA, family history, ethnic origin and prostate ultrasound results were used for risk assessment using the online nomograms. Mononuclear cells were obtained by differential gel centrifugation from 8 ml of blood and CPCs were identified using double immunomarcation with anti-PSA and anti-P504S. A CPC was defined as a cell expressing PSA and P504S and defined as negative/positive. Biopsies were classified as cancer/no-cancer. Areas under the curve (AUC) for each parameter were calculated and compared and diagnostic yields were calculated. Results: 1,223 men aged>55 years participated, 467 (38.2%) had a biopsy positive for cancer of whom 114/467 (24.4%) complied with the criteria for active observation. Area under the curve analysis showed CPC detection to be superior (p<0.001), avoiding 57% of potential biopsies while missing 4% of clinically significant prostate cancers. Conclusions: The CPC detection was superior to the nomograms in predicting the presence of prostate cancer at initial biopsy; its high negative predictive value potentially reduces the number of biopsies while missing few significant cancers, being superior to the nomograms in this aspect. Being a positive/negative test the detection of CPCs avoids defining a cutoff value which may differ between populations

A comparison of 3 on-line nomograms with the detection of primary circulating prostate cells to predict prostate cancer at initial biopsy. / Comparación de 3 nomogramas en línea con la detección de las células primarias circulantes de la próstata para predecir el cáncer de próstata en la biopsia inicial.

INTRODUCTION: The use of nomograms which include the PSA may improve the predictive power of obtaining a prostate biopsy (PB) positive for cancer. We compare the use of three on-line nomagrams with the detection of primary malignant circulating prostate cells (CPCs) to predict the results of an initial PB in men with suspicion of prostate cancer. METHODS AND PATIENTS: Consecutive men with suspicion of prostate cancer underwent a 12 core TRUS prostate biopsy; age, total serum PSA, percent free PSA, family history, ethnic origin and prostate ultrasound results were used for risk assessment using the online nomograms. Mononuclear cells were obtained by differential gel centrifugation from 8ml of blood and CPCs were identified using double immunomarcation with anti-PSA and anti-P504S. A CPC was defined as a cell expressing PSA and P504S and defined as negative/positive. Biopsies were classified as cancer/no-cancer. Areas under the curve (AUC) for each parameter were calculated and compared and diagnostic yields were calculated. RESULTS: 1,223 men aged>55 years participated, 467 (38.2%) had a biopsy positive for cancer of whom 114/467 (24.4%) complied with the criteria for active observation. Area under the curve analysis showed CPC detection to be superior (p<0.001), avoiding 57% of potential biopsies while missing 4% of clinically significant prostate cancers. CONCLUSIONS: The CPC detection was superior to the nomograms in predicting the presence of prostate cancer at initial biopsy; its high negative predictive value potentially reduces the number of biopsies while missing few significant cancers, being superior to the nomograms in this aspect. Being a positive/negative test the detection of CPCs avoids defining a cutoff value which may differ between populations.

Development and validation of a feline abdominal palpation model and scoring rubric.

Simulation in veterinary education enables clinical skills practice without animal use. A feline abdominal palpation model was created that allows practice in this fractious species. This study assessed the model and rubric using a validation framework of content evidence, internal structure and relationship with level of training. Content Evidence: Veterinarians accepted this model as a helpful training tool for students (median=4 on five-point Likert scale). Internal Structure Evidence: G-coefficients were low for first- and second-year students (0.28 and 0.23), but were acceptable for veterinarians (0.61). Internal consistency values (0.24, 0.42 and 0.67) followed a similar pattern. Thus, scores were more reliable for veterinarians than for the students. Evidence of Relationship with Level of Training: Although level of training impacted reliability, its effect on performance scores was inconsistent. Analysis of variance (ANOVA) identified no differences among the groups of students and veterinarians. However, effect size between first- and third-year students was medium to large (0.62). Effect sizes between the veterinarians and student groups were small. Although the model and rubric appeared valid for experts, modifications would be necessary to generate reliable scores for students. These results allow greater understanding of the needs of students utilising a low-fidelity model.

Consideraciones clínicas de la expresión de P504S y metaloproteinasa de matriz 2 en células prostáticas circulantes en sangre diseminadas como resultado de una biopsia prostática trans-rectal guiada por ecografía / Expression of P504S and matrix metalloproteinase-2 in circulating prostate cells disseminated as a result of transrectal ultrasound guided biopsy as determined by immunocytochemistry: Clinical implications

OBJETIVO: la manipulación quirúrgica del cáncer tiene la potencialidad de aumentar la diseminación de células cancerosas al torrente sanguíneo y con esto el riesgo de metástasis. Presentamos el efecto de la biopsia prostática en la diseminación de estas células así como sus características fenotípicas. MÉTODOS: Se incluyeron cincuenta hombres que fueron sometidos a una biopsia prostática trans rectal como sospecha de cáncer de próstata en nuestro estudio. Se recolectaron muestras sanguíneas inmediatamente antes de la biopsia, una hora y 24 horas posterior a la misma, para detección de células prostáticas en sangre (CPC) así como para determinar sus características fenotípicas utilizando inmunocitoquímica estándar con anti PSA y luego caracterizarlas utilizando anti P504S y anti matriz de metaloproteinasa 2 (MMP-2). RESULTADOS: Catorce hombres (28%) tuvieron cáncer de próstata en la biopsia, 13 de estos fueron P504S + y MMP-2 + previo a la biopsia. Una hora posterior a la biopsia existió una mezcla de P504S + y P504S - así como de MMP2 + y MMP2 - en pacientes con biopsia positiva para cáncer, niveles que se igualaron a los pre biopsia luego de 24 horas. En pacientes negativos para cáncer, se detectaron células circulantes P504S - y MMP-2 -, algunas de ellas se mantuvieron por más de 24 horas. CONCLUSIONES: La biopsia prostática puede causar diseminación de células prostáticas malignas y benignas a la circulación y la mayoría son eliminadas dentro de las primeras 24 horas. No existió conversión de pacientes con cáncer de CPCs negativos a positivos lo que sugiere que la capacidad inherente de las células prostáticas de diseminar es más importante que el efecto de la biopsia prostática

OBJECTIVES: Surgical manipulation of cancer has been shown to increase blood borne cancer cell dissemination and increase the risk of metastasis. We present the effect of prostate biopsy on prostate cell dissemination and the phenotypic characteristics of these cells. METHODS: 50 men undergoing initial prostate biopsy for suspicion of prostate cancer were studied. Blood samples were taken immediately before, and 1 and 24 hours after biopsy for circulating prostate cells (CPC) determination and phenotypic characterization. CPCs were detected and counted using standard immunocytochemistry using anti-PSA and then characterized using anti-P504S and anti-matrix metalloproteinase-2 (MMP-2). RESULTS: 14 (28%) men had cancer detected on biopsy. 13/14 had P504S (+) and MMP-2 (+) cells detected prior to biopsy. One hour after biopsy there was a mixture of P504S (+) and P504S (-) cells detected, as well as MMP-2 (+) and MMP-2 (-) cells detected. 24 hours after biopsy the same 13/14 men remained positive, although the number of CPCs increased 1 hour after biopsy and then the numbers decreased to prebiopsy levels after 24 hours. In cancer negative men, P504S (-) and MMP-2 (-) cells were detected, some of these cells persisted 24 hours after biopsy. CONCLUSIONS: Prostate biopsy causes dissemination of prostate cells into the circulation, both malignant and benign; the majority of them are cleared within 24 hours. There was no conversion of negative to positive result in men with cancer, this suggests that the inherent capacity of malignant CPCs to disseminate is more important than the effect of dissemination caused by prostate biopsy

Effect of androgen blockade on HER-2 and matrix metalloproteinase-2 expression on bone marrow micrometastasis and stromal cells in men with prostate cancer.

INTRODUCTION: HER-2 has been associated with castrate resistant prostate cancer and matrix metalloproteinase-2 (MMP-2) in the dissemination and invasion of tumor cells as well as activating angiogenesis. We present an immunocytochemical study of the effect of androgen blockade on the expression of HER-2 and MMP-2 in bone marrow micrometastasis and the surrounding stromal cells in men with prostate cancer. METHODS AND PATIENTS: A cross-sectional study of men with prostate cancer. Touch preps were obtained from bone marrow biopsies of men with prostate cancer, before and after radical prostatectomy and during androgen blockade. Micrometastasis detected with anti-PSA immunocytochemistry underwent processing with anti-HER-2 and anti-MMP-2 immunocytochemistry. Patients were defined as HER-2 positive or negative, MMP-2 negative or an MMP-2 pattern described as border or central and stromal MMP-2 defined as positive or negative. The expression of the biomarkers was compared before and after primary treatment and during androgen blockade in relation to the serum PSA at the time of sampling and duration of androgen blockade. RESULTS: 191 men participated, 35 men before surgery and 43 after surgery; there were no significant differences in HER-2 expression between groups, there was no MMP-2 expression centrally or stromal expression of MMP-2. In men with androgen blockade, HER-2 expression was significantly higher; there was a trend for increasing HER-2 expression up to 5 years; central MMP-2 expression significantly increased after 3 years, while stromal MMP-2 significantly increased after 6 years. MMP-2 expression both in micrometastasis and stroma was significantly associated with HER-2 expression. Expression of MMP-2 at the border of the micrometastasis was not associated with HER-2 expression and occurred in the absence of androgen blockade. CONCLUSIONS: Androgen blockade decreases serum PSA by eliminating HER-2 negative prostate cancer cells. However, there is early selection of HER-2 positive cancer cells which leads to androgen independence and to increased expression of MMP-2 activity in the micrometastasis. The increased MMP-2 activity in the micrometastasis increases the expression of MMP-2 in the surrounding stromal cells and thus could promote angiogenesis and tumor growth resulting in macrometastatic androgen independent disease.

A performance analysis of the presence of malignant circulating prostate cells as a predictive factor for the detection of prostate cancer in the first, second and third prostate biopsy.

OBJECTIVES: Serum prostate specific antigen and digital rectal examination are the tests used as screening tests to detect prostate cancer. However, only approximately 30% of men with suspicion of cancer have it confirmed on prostate biopsy, and not all of these need treatment. Detection of circulating tumor cells in localized prostate cancer has given variable results, but it could be a useful complementary screening tool to detect prostate cancer in men with abnormal screening tests before the evaluation with prostate biopsy. This may be more so in subsequent biopsies where serum PSA has a decreased diagnostic yield. To evaluate the diagnostic yield of the detection of CPCs as a complementary PC screening test in a population fulfilling criteria for an initial, second and third prostate biopsy for suspicion of PC. METHODS: A prospective screening study of consecutive patients aged 45-80 years presenting to the urologist for PC screening. Inclusion criteria were PSA >4.0 ng/ml, PSA velocity >0.35 ng/ml/year and/or DRE suspicious for cancer. Patients fulfilling inclusion criteria had blood taken for CPC detection and then underwent 12-core transrectal prostate biopsy. Double immune-his-tochemical staining with anti-PSA and anti-P504S was used to detect CPCs. Both cytologist and pathologist were blinded to the results of the biopsy, CPC results and clinical details. The diagnostic yield of the presence or absence of CPC was evaluated; the prostate biopsy was classified as cancer or no-cancer. RESULTS: 282 men participated, 83 undergoing of these undergoing a second and 38 a third biopsy, with a mean age of 66.2 ± 8.9 years and a median serum PSA of 5.10 ng/ml, 5.45 ng/ml and 6.45 ng/ml for first, second and third biopsies. Cancer was detected in 33,6%, 10.8% and 29.0% of first, second and third biopsies respectively, CPCs were detected in 36.9%, 21.7% and 36.8% of the patients. Sensibility, specificity and negative predictive value were 86% ,91% and 94% for the first biopsy, 89%, 87% and 99% for the second and 100% , 89% and 100% for third biopsy respectively. All the CPC determinations were interpretable. There were 11 false negative cases, all with small low grade tumors. Of the 29 men with a false positive CPC, 8/10 had cancer detected in the subsequent biopsy. CONCLUSIONS: The use of CPC detection could be useful as a complementary prostate cancer screening test, especially for excluding cancer, and including patients with indications for repeat biopsies. Men with a false positive CPC detection had a high risk of detecting cancer in the succeeding biopsy.

Análisis del desempeño de la presencia de células prostáticas malignas circulantes como factor predictivo para la detección de cáncer de próstata en la primera, segunda y tercera biopsia prostática / A performance analysis of the presence of malignant circulating prostate cells as a predictive factor for the detection of prostate cancer in the first, second and third prostate biopsy

OBJETIVO: El PSA en conjunto con el tacto rectal son los exámenes más utilizados para el cribado de cáncer de próstata (CP), sin embargo, en solo el 30% de estos pacientes se confirma el diagnóstico. En el presente estudio evaluamos el rendimiento diagnóstico de la detección de células prostáticas circulantes malignas (mCPC) para la detección precoz del CP en pacientes que cumplen con los criterios para realización de una o más biopsias prostáticas. MÉTODO: Estudio prospectivo, ciego, con reclutamiento consecutivo de pacientes entre 45-80 años, con sospecha de CP. Criterios de inclusión: PSA sérico >4,0 ng/ml, elevación >0,75 ng/ml/año, tacto rectal sospechoso de cáncer. La detección de mCPC fue realizada por inmunohistoquímica con doble marcación hacia el PSA y P504S. Se evalúo el rendimiento diagnóstico de la presencia o ausencia de mCPC comparándolos con los resultados de la biopsia prostática, la cual se clasificó como cáncer o no cáncer. RESULTADOS: Participaron 282 hombres; 83 de los cuales fueron sometidos a una segunda biopsia y 38 a una tercera. La edad media fue 66.2 ± 8.9 años; una media de PSA de 5,10, 5,45 y 6,45 ng/dl para la primera, segunda y tercera biopsia respectivamente. Se diagnosticó CP en 33.6%, 10,8% y 29,0% y las mCPC se detectaron en 36,9%, 21,7% y 36,8% de la primera, segunda y tercera biopsia respectivamente. Con una sensibilidad, especificidad y valor predictivo negativo de 86.2%, 90.8% y 94.3% para la primera biopsia; 89%, 87% y 99% para la segunda y 100%, 89% y 100% para la tercera biopsia respectivamente. Ocurrieron 11 casos de falsos negativos, con un CP pequeño y de bajo grado. De los 29 pacientes con un falso positivo para CPC, 8/10 tuvieron un cáncer detectado en la siguiente biopsia. CONCLUSIÓN: El uso de la detección de mCPC puede ser un método útil como examen complementario a los actualmente en uso para la detección de cáncer prostático, y durante el seguimiento de pacientes con PSA persistentemente elevado para determinar la necesidad de una re biopsia. Las mCPCs tienen un especial valor por su alto valor predictivo negativo en pacientes con un PSA ≥4.0ng/ml (AU)

OBJECTIVES: Serum prostate specific antigen and digital rectal examination are the tests used as screening tests to detect prostate cancer. However, only approximately 30% of men with suspicion of cancer have it confirmed on prostate biopsy, and not all of these need treatment. Detection of circulating tumor cells in localized prostate cancer has given variable results, but it could be a useful complementary screening tool to detect prostate cancer in men with abnormal screening tests before the evaluation with prostate biopsy. This may be more so in subsequent biopsies where serum PSA has a decreased diagnostic yield. To evaluate the diagnostic yield of the detection of CPCs as a complementary PC screening test in a population fulfilling criteria for an initial, second and third prostate biopsy for suspicion of PC. METHODS: A prospective screening study of consecutive patients aged 45-80 years presenting to the urologist for PC screening. Inclusion criteria were PSA >4.0ng/ml, PSA velocity >0.35ng/ml/year and/or DRE suspicious for cancer. Patients fulfilling inclusion criteria had blood taken for CPC detection and then underwent 12-core transrectal prostate biopsy. Double immune-his-to chemical staining with anti-PSA and anti-P504S was used to detect CPCs. Both cytologist and pathologist were blinded to the results of the biopsy, CPC results and clinical details. The diagnostic yield of the presence or absence of CPC was evaluated; the prostate biopsy was classified as cancer or no-cancer. RESULTS: 282 men participated, 83 undergoing of these undergoing a second and 38 a third biopsy, with a mean age of 66.2 ± 8.9 years and a median serum PSA of 5.10ng/ml, 5.45ng/ml and 6.45ng/ml for first, second and third biopsies. Cancer was detected in 33,6%, 10.8% and 29.0% of first, second and third biopsies respectively, CPCs were detected in 36.9%, 21.7% and 36.8% of the patients. Sensibility, specificity and negative predictive value were 86%, 91% and 94% for the first biopsy, 89%, 87% and 99% for the second and 100%, 89% and 100% for third biopsy respectively. All the CPC determinations were interpretable. There were 11 false negative cases, all with small low grade tumors. Of the 29 men with a false positive CPC, 8/10 had cancer detected in the subsequent biopsy. CONCLUSIONS: The use of CPC detection could be useful as a complementary prostate cancer screening test, especially for excluding cancer, and including patients with indications for repeat biopsies. Men with a false positive CPC detection had a high risk of detecting cancer in the succeeding biopsy (AU)

Redefining micrometastasis in prostate cancer - a comparison of circulating prostate cells, bone marrow disseminated tumor cells and micrometastasis: Implications in determining local or systemic treatment for biochemical failure after radical prostatectomy.

The presence of cells positive for cytokeratins or prostate-specific antigen (PSA) in bone marrow aspirates (BMAs) has been used to indicate the presence of micrometastasis. The aim of this prospective study of prostate cancer patients was to determine the presence of prostate cells in blood and BMAs and to compare them with bone marrow biopsy touch prep samples. The results indicated that there was a satisfactory concordance between circulating prostate cells (CPCs) in blood and disseminated tumor cells (DTCs) in BMAs for all Gleason scores (κ>0.50). However, neither were concordant with the presence of prostate cells in bone marrow biopsies except for high-grade tumors, Gleason 8 and 9. Phenotypic characteristics of CPCs and DTCs were identical (κ>0.9) but were different than cells detected in bone marrow biopsies (κ<0.2). The expression of matrix metalloproteinase-2 (MMP-2) in bone marrow biopsies was positively associated with the Gleason score (trend Chi-squared <0.05) and may explain the differences between the presence of DTCs and the presence of prostate cells in bone marrow biopsies. If the presence of DTCs was used to indicate micrometastatic disease, 20% of patients would be misclassified compared to micrometastasis defined as patients with a positive biopsy. This may have clinical implications for patients with low-grade tumors.

Rendimiento diagnóstico de la detección de células prostáticas malignas en la circulación sanguínea para la detección précoz del cáncer prostático: una comparación con la biopsia prostática / Diagnostic performance of malignant prostatic cells detection in blood for early detection of prostate cancer: comparison to prostatic biopsy

OBJETIVO: El PSA y el tacto rectal son los exámenes utilizados para el tamizaje de cáncer prostático (CP), pero solo en el 30% de los pacientes con sospecha de cáncer prostático se confirma el diagnóstico. La detección de células prostáticas circulantes en sangre puede ser una herramienta útil para la detección de cáncer prostático en estos pacientes.Evaluar el rendimiento diagnóstico de la detección de CPCm para la detección precoz del CP, en una población que cumple los criterios para la realización de una biopsia prostática por sospecha de CP.MÉTODO: Estudio prospectivo, con reclutamiento consecutivo de pacientes entre 45-80 años, con sospecho de CP. Criterios de inclusión: PSA sérico >4,0 ng/ml, elevación >0,35 ng/ml/año, tacto rectal sospechoso de cáncer. Pacientes con alguno de estos criterios fue sometido a una biopsia prostática transrectal y a la determinación de CPCm en sangre. La detección de CPCm fue realizada por inmunohistoquímica con doble marcación hacia el PSA y P504S. Tanto el citólogo como el patólogo fueron ciegos al resultado de las CPCm y la BP, así como a los datos clínicos. Se evalúo el rendimiento diagnóstico de la presencia o ausencia de CPCm. La biopsia se clasificó como cáncer o no cáncer. Los pacientes fueron divididos entre 1) PSA ≥4,0ng/ml y 2) PSA <4,0ng/ml y cumple con otro criterio para una BP.RESULTADOS: Participaron 228 hombres; edad media de 66.8 ± 8.8 años; PSA mediana de 5.15 ng/dl. Se diagnosticó CP en 28.6% de los casos mediante la BP y las CPCm se detectaron en 31% de todos los pacientes. Con una sensibilidad, especificidad y valor predictivo negativo de 86.2%, 90.8% y 94.3%, respectivamente. Razón de verosimilitud negativa y positiva de 0,15 y 9,36. En hombres con un PSA <4,0ng/ml, hubo 13,3% con CP, una sensibilidad y especificidad de 83,3% y 84,6% y valor predictivo negativo de 97,1%. Ocurrieron 9 casos de falsos negativos, con un CP pequeño y de bajo grado(AU)

CONCLUSIÓN: La detección de CPCm podría ser útil como examen complementario en la detección de cáncer prostático, en especial para su exclusión, incluido pacientes con PSA < de 4 ng/ml(AU)

OBJECTIVES: Serum prostate specific an-tigen and digital rectal examination are the tests used as screening tests to detect prostate cancer. However, only approximately 30% of men with suspicion of can-cer have it confirmed on prostate biopsy, and not all of these need treatment. Detection of circulating tumor cells in localized prostate cancer has given variable re-sults, but it could be a useful complementa-ry screening tool to detect prostate cancer in men with abnormal screening tests before the evaluation with prostate biopsy.To evaluate the diagnostic yield of the detection of mCPC as a complementary PC screening test in a po-pulation fulfilling criteria for a prostate biopsy for sus-picion of PC.METHODS: A prospective screening study of consecuti-ve patients aged 45-80 years presenting to the urologist for PC screening. Inclusion criteria were PSA >4.0ng/ml, PSA velocity >0.35ng/ml/year and/or DRE suspi-cious for cancer. Patients fulfilling inclusion criteria had blood taken for mCPC detection and then underwent 12-core transrectal prostate biopsy. Double immune-histochemical staining with anti-PSA and anti-P504S was used to detect mCPC. Both cytologist and pathologist were blinded to the results of the biopsy, mCPC results and clinical de-tails. The diagnostic yield of the presence or absence of mCPC was evaluated; the prostate biopsy was classi-fied as cancer or no-cancer(AU)

RESULTS: 228 men participated, with a mean age of 66.8 ± 8.8 years and a median serum PSA of 5.15ng/ml. 28.6% of the biopsies were positive for PC, and mCPC were detected in 31.0% of all cases. Sensibility, specifici-ty and negative predictive value were 86.2%, 90.8% and 94.3% respectively. The negative and positive like-lihood ratios were 9.36 and 0.15. In men with a PSA <4.0ngml, 13.3% had cancer detected on biopsy, with a sensibility and specificity for mCPC detection of 83.3% and 84.6% and negative predictive value of 97.1%. All the mCPC determinations were interpretable. There were 9 false negative cases, all with small low grade tumors.CONCLUSIONS: The use of mCPC detection could be useful as a complementary prostate cancer screening test, especially for excluding cancer, including patients with a serum PSA <4.0ng/ml(AU)

Diagnostic performance of malignant prostatic cells detection in blood for early detection of prostate cancer: comparison to prostatic biopsy.

OBJECTIVES: Serum prostate specific antigen and digital rectal examination are the tests used as screening tests to detect prostate cancer. However, only approximately 30% of men with suspicion of cancer have it confirmed on prostate biopsy, and not all of these need treatment. Detection of circulating tumor cells in localized prostate cancer has given variable results, but it could be a useful complementary screening tool to detect prostate cancer in men with abnormal screening tests before the evaluation with prostate biopsy. To evaluate the diagnostic yield of the detection of mCPC as a complementary PC screening test in a population fulfilling criteria for a prostate biopsy for suspicion of PC. METHODS: A prospective screening study of consecutive patients aged 45-80 years presenting to the urologist for PC screening. Inclusion criteria were PSA >4.0 ng/ml, PSA velocity >0.35 ng/ml/year and/or DRE suspicious for cancer. Patients fulfilling inclusion criteria had blood taken for mCPC detection and then underwent 12-core transrectal prostate biopsy. Double immune-histochemical staining with anti-PSA and anti-P504S was used to detect mCPC. Both cytologist and pathologist were blinded to the results of the biopsy, mCPC results and clinical details. The diagnostic yield of the presence or absence of mCPC was evaluated; the prostate biopsy was classified as cancer or no -cancer. RESULTS: 228 men participated, with a mean age of 66.8 ± 8.8 years and a median serum PSA of 5.15 ng/ml. 28.6% of the biopsies were positive for PC, and mCPC were detected in 31.0%of all cases. Sensibility, specificity and negative predictive value were 86.2%, 90.8% and 94.3% respectively. The negative and positive like-lihood ratios were 9.36 and 0.15. In men with a PSA <4.0ngml, 13.3% had cancer detected on biopsy, with a sensibility and specificity for mCPC detection of 83.3% and 84.6% and negative predictive value of 97.1%. All the mCPC determinations were interpretable. There were 9 false negative cases, all with small low grade tumors. CONCLUSIONS: The use of mCPC detection could be useful as a complementary prostate cancer screening test, especially for excluding cancer, including patients with a serum PSA <4.0 ng/ml.

Tumour necrosis factor (TNF)alpha -308 G/G promoter polymorphism and TNFalpha levels correlate with a better response to adalimumab in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the influence of -308 tumour necrosis factor-alpha (TNFalpha) promoter polymorphism and circulating TNFalpha levels in the clinical response to adalimumab treatment in patients with rheumatoid arthritis (RA). METHODS: Eighty-one patients with active RA were genotyped for the -308 TNFalpha polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and subdivided into two groups for each polymorphism (G/A and G/G genotype). All received 40 mg of adalimumab subcutaneously every other week. We compared the groups' clinical responses to adalimumab at 8, 16, and 24 weeks using the Disease Activity Score in 28 joints (DAS28). RESULTS: Both groups showed a significant improvement from baseline. A significant difference between groups was found at week 24. We found that 88.2% of G/G versus 68.4% of G/A for the -308 polymorphism were DAS28 responders (p = 0.05). The score improvement at week 24 was 2.5 +/- 1.3 in the G/G group and 1.8 +/- 1.3 in the G/A group for the -308 polymorphism (p = 0.04). The median of serum TNFalpha levels of the G/A group were lower than those of the G/G group, and statistically different at weeks 8 and 24 (p < 0.039 and p < 0.043). When comparing baseline levels to those achieved at 8, 16, and 24 weeks for the whole group, only responder patients showed a statistically significant overall increase in TNFalpha over time (p < 0.000001). CONCLUSION: A relationship between DAS28 improvement, the -308 G/G polymorphism, and increased circulating TNFalpha levels was found in Chilean RA patients treated with adalimumab.

Effect of chronic exposure to excess dietary copper and dietary selenium supplementation on liver specimens from rats.

OBJECTIVE: To determine the effects of chronic exposure to excess dietary copper (Cu) on liver specimens from rats and the effects of dietary selenium (Se) supplementation in experimental Cu toxicosis. ANIMALS: 60 weanling male Fischer 344 rats. PROCEDURE: Rats were randomly assigned to 4 groups of 15 rats each and fed 1 of the following 4 diets: high Cu (500 microg/g)/adequate Se (0.2 microg/g); high Cu (500 microg/g)/supplemented Se (2 microg/g); adequate Cu (18 microg/g)/adequate Se (0.2 microg/g); or, adequate Cu (18 microg/g)/supplemented Se (2 microg/g). Five rats per group were euthanatized after 3, 6, and 12 months, and liver specimens were obtained for histologic examination, histochemistry, metal analysis by atomic absorption spectrophotometry, measurement of glutathione peroxidase activity, and assessment of lipid peroxidation, using quantification of malondialdehyde (MDA) by the thiobarbituric acid reaction. RESULTS: Hepatic Cu concentration was significantly higher in rats fed high Cu diets (range, 9 to 18 microg/g of tissue [wet weight]), compared with rats receiving adequate Cu diets (4.0 to 5.7 microg/g of tissue). Rats fed high-Cu diets for 3, 6, and 12 months had mild multifocal hepatitis often surrounding necrotic foci. However, an increase in hepatic MDA content, indicative of lipid peroxidation, was not detected in these rats. Development of morphologic changes was not prevented by use of dietary Se supplementation. CONCLUSION AND CLINICAL RELEVANCE: Long-term exposure to excess dietary Cu caused mild hepatic lesions in Fischer 344 rats. Dietary Se supplementation did not prevent hepatic damage in rats with Cu toxicosis.

[Characteristics of hospitalization of patients with rheumatic diseases admitted to a tertiary care hospital]. / Características de la hospitalización reumatológica en un hospital de nivel terciario.

BACKGROUND: The diagnostic profile of patients with rheumatic diseases admitted to a general hospital is variable. AIM: To report the epidemiological profile of patients with rheumatic diseases admitted to a tertiary care hospital. MATERIAL AND METHODS: All admissions to a Medicine ward of a general hospital and seen by the Rheumatology team were prospectively registered during one year in 1999. Patients were classified as primarily admitted for a rheumatic disease or admitted for other cause that required a consultation with the Rheumatology team. RESULTS: One hundred forty five admissions due to rheumatic diseases were registered. Of these, 82 were due to primary rheumatic diseases. Systemic lupus erythematosus, rheumatoid arthritis and vasculitis were the main diagnoses and the mean hospital stay was 18.5 days. Sixty three patients required a consultation with the Rheumatology team specially due to osteoarthritis and crystal induced diseases. CONCLUSIONS: Admissions due to rheumatic diseases are prolonged, correspond to 0.46% of all admissions and the main responsible disease is systemic lupus erythematosus.

[Nocardia asteroides infection in a patient with systemic lupus erythematosus]. / Infección por Nocardia asteroides en un paciente con lupus eritematoso sistémico.

Nocardia asteroides infection are unusually observed in systemic Lupus erithematous (SLE) patients. They are generally associated to steroidal and immunosuppressive therapy. We report a 24 years old female with SLE diagnosed in 1994 who developed a severe preeclampsia in her first pregnancy requiring emergency caesarean section. Post partum acute renal failure and type IV lupus nephropathy were treated with hemodialysis, methylprednisolone, cyclophosphamide and prednisone. Three months later, while she was receiving the fourth cyclophosphamide dose, she presented with a pleuro pneumonia and occipital abscess, both caused by Nocardia asteroides. She was treated with cotrimoxazole + cefixime and pleural decortication was required. Five months later, she developed Meningitis caused by Nocardia asteroides and hydrocephalus. She was treated with ceftriaxone, vancomycin, cotrimoxazole and ventricular shunting procedure. Two months later, a retroperitoneal abscess was diagnosed and surgically drained but the patient died, due to a methicillin-resistant Staphylococcus aureus septicemia.