Programa MICCAP (Manejo de la Insuficiencia Cardiaca en Cardiología y en Atención Primaria): mejorando el manejo del paciente con insuficiencia cardiaca / Management of heart failure in cardiology and primary care (MICCAP) program: Improving the management of patients with heart failure

A pesar de los tratamientos actuales,la morbilidad y la mortalidad de los pacientes con insuficiencia cardiaca continúan siendo elevadas. El diagnóstico tardío, el tratamiento insuficiente de la insuficiencia cardiaca (por ejemplo no emplear los fármacos apropiados, prescribir dosis más bajas que las recomendadas, etc.) y la pobre coordinación entre los diferentes niveles asistenciales pueden explicar, al menos en parte, estos datos. El programa MICCAP se ha desarrollado con el objetivo de optimizar el manejo integrado de los pacientes con insuficiencia cardiaca entre atención primaria y cardiología, a través de la mejora en la coordinación entre ambos niveles asistenciales y la educación médica continuada, reforzando las habilidades diagnósticas y terapéuticas de los médicos de atención primaria en el campo de la insuficiencia cardiaca. En este manuscrito se resumen el racional y los objetivos del programa MICCAP

Despite current treatments, morbidity and mortality of patients with heart failure remain high. The late diagnosis of heart failure, the insufficient heart failure treatment (i.e. not using the appropriate drugs, prescribing lower doses of drugs than recommended, etc.), and a poor coordination between different health care levels, may explain, at least in part, these figures. The Management of Heart Failure in Cardiology and Primary Care (MICCAP) program has been developed with the aim of optimising the integrated management of patients with heart failure between Primary Care and Cardiology, through the improvement of coordination between both health care levels. This includes continuous medical education to reinforce the diagnostic and therapeutic skills of general practitioners in the field of heart failure. The rationale and objectives of the MICCAP program are summarised in this article

[Management of heart failure in cardiology and primary care (MICCAP) program: Improving the management of patients with heart failure]. / Programa MICCAP (Manejo de la Insuficiencia Cardiaca en Cardiología y en Atención Primaria): mejorando el manejo del paciente con insuficiencia cardiaca.

Despite current treatments, morbidity and mortality of patients with heart failure remain high. The late diagnosis of heart failure, the insufficient heart failure treatment (i.e. not using the appropriate drugs, prescribing lower doses of drugs than recommended, etc.), and a poor coordination between different health care levels, may explain, at least in part, these figures. The Management of Heart Failure in Cardiology and Primary Care (MICCAP) program has been developed with the aim of optimising the integrated management of patients with heart failure between Primary Care and Cardiology, through the improvement of coordination between both health care levels. This includes continuous medical education to reinforce the diagnostic and therapeutic skills of general practitioners in the field of heart failure. The rationale and objectives of the MICCAP program are summarised in this article.

IL28RA polymorphism is associated with early hepatitis C virus (HCV) treatment failure in human immunodeficiency virus-/HCV-coinfected patients.

Due to the poor rate of response to hepatitis C virus (HCV) with pegylated interferon and ribavirin treatment in HCV/HIV coinfected patients, key factors for predicting failure would be useful. We performed a retrospective study on 291 patients on HCV treatment, who had early virological response (EVR) data. IL28B and IL28RA polymorphisms were performed using the GoldenGate(®) assay. Unfavourable genotypes at IL28B (rs12980275 AG/GG and rs8099917 GT/GG) and an unfavourable allele at IL28RA (rs10903035 G) were associated with early treatment failure. However, only the rs12980275 AG/GG genotype and rs10903035 G allele remained independently associated with early failure in the overall population (OR = 4.15 (95% CI = 1.64-10.54) and OR = 2.00 (95% CI = 1.19-3.36), respectively) as well as in GT1/4 patients (OR = 5.07 (95% CI = 1.81-14.22) and OR = 2.03 (95% CI = 1.13-3.66), respectively). Next, a decision tree showed early treatment failure increased from 37.1% to 65.5% when the unfavourable rs12980275 AG/GG and rs10903035 AG/GG genotypes and HCV-RNA≥ 500.000 IU/mL were taken into account in GT1/4 patients. In contrast, the failure rate decreased from 37.1% to 11.9% when the favourable rs12980275 AA and rs10903035 AA genotypes were detected. The percentage of patients correctly classified was 78.4%, and AUROC was 0.802 ± 0.028. Regarding GT3 patients, the presence of the GCGCA haplotype (all unfavourable alleles) was associated with early treatment failure, while no association was observed for the IL28B polymorphisms. In conclusion, the IL28RA polymorphism was associated with early treatment failure independently of the IL28B SNPs. The combination of IL28B and IL28RA polymorphisms might be a valuable tool for predicting early treatment failure before starting HCV treatment.

Association of torque teno virus (TTV) and torque teno mini virus (TTMV) with liver disease among patients coinfected with human immunodeficiency virus and hepatitis C virus.

Torque teno virus (TTV) and torque teno mini virus (TTMV) have been potentially related to liver diseases. The aim of the study was to quantify TTV and TTMV in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients to study the relationship between the TTV and TTMV viral loads and the severity of liver disease. We carried out a cross-sectional study in 245 patients coinfected with HIV and HCV (HIV/HCV-group), 114 patients monoinfected with HIV (HIV-group), and 100 healthy blood donors (Control-group). Plasma samples were tested for TTV and TTMV by quantitative real-time polymerase chain reaction (PCR). The prevalences of TTV and TTMV infections in the HIV/HCV-group and the HIV-group were significantly higher than the Control-group (p < 0.05). Furthermore, TTV and TTMV coinfections were found in 92.2 % (226/245) in the HIV/HCV-group, 84.2 % (96/114) in the HIV-group, and 63 % (63/100 %) in the Control-group (p ≤ 0.05). HIV/HCV-coinfected patients with HIV viral load ≥50 copies/mL and patients with severe activity grade had the highest viral loads of TTV and TTMV (p ≤ 0.05). HIV/HCV-coinfected patients with high TTV load (>2.78 log copies/µL) had increased odds of having advanced fibrosis or severe necroinflammatory activity grade in the liver biopsy. Moreover, HIV/HCV-coinfected patients with high TTMV load (>1.88 log copies/µL) had decreased odds of having no/minimal fibrosis and no/mild activity grade, and increased odds of having a high fibrosis progression rate. In conclusion, TTV and TTMV might play a role in the development of liver disease in immunodeficiency patients, such as the patients coinfected with HIV and HCV.

Use of transient elastography (FibroScan®) for the noninvasive assessment of portal hypertension in HIV/HCV-coinfected patients.

The hepatic venous pressure gradient (HVPG) is the gold standard for assessing portal pressure and correlates with the occurrence of portal hypertension (PH)-related complications. Transient elastography (TE) is a new, highly accurate noninvasive technique, which enables us to evaluate hepatic fibrosis to detect advanced fibrosis and cirrhosis. We performed a hepatic haemodynamic study and TE in 38 HIV/HCV-coinfected patients. The association between HVPG and liver stiffness was assessed by linear regression. The diagnostic value of TE was assessed by receiver operating characteristic (ROC) curves. We considered clinically significant PH as an HVPG ≥ 10 mmHg and severe PH as an HVPG ≥ 12 mmHg. A total of 38 HIV/HCV-coinfected patients were included. Twenty-eight patients (73.7%) had clinically significant PH (HVPG ≥ 10 mmHg), and 23 (60.5%) of these had severe PH (HVPG ≥ 12 mmHg). We found a statistically significant association between liver stiffness (kPa) and HVPG (r(2) = 0.46, P < 0.001, straight line equation HVPG=7.4 + 0.204*TE). The areas under the ROC curves were 0.80 [95% confidence interval (CI), 0.64-0.97] and 0.80 (95% CI, 0.66-0.94) for the prediction of HVPG ≥ 10 and ≥ 12 mmHg, respectively. Our data suggest that TE can predict the presence of clinically significant and severe PH in HIV/HCV-coinfected patients.

Soluble Fas and Fas ligand in HIV/HCV coinfected patients and impact of HCV therapy.

The aim of this study was to evaluate the influence of clinical and epidemiological characteristics of 183 HIV/HCV coinfected patients and HCV clearance after antiviral treatment on serum sFas and sFasL levels. Thirty out of 183 patients underwent HCV antiviral therapy with IFN-α + RBV for a duration of 48 weeks. HCV genotype 1 and homeostasis model assessment for insulin resistance (HOMA-IR) had a significant positive relationship, and CD4+/µL had a significant negative relationship with sFas (R-square = 0.582; p < 0.001) and sFasL (R-square = 0.216; p < 0.001) in multivariate linear regression analysis. HCV genotype 1 was the only significant variable associated with the sFas/sFasL ratio (R-square = 0.201; p < 0.001). sFas and sFasL levels had positive significant correlations with serum sICAM-1, sVCAM-1, and HOMA levels (p < 0.05). Among patients on IFN-α + RBV therapy, 15 patients showed a sustained virologic response (SVR), while 15 patients were non-responders (NR). Patients with SVR had significant decreases in sFas (p = 0.008) and sFas/sFasL ratio (p = 0.002), while non-responders had a significant increase in sFasL values (p = 0.013). In conclusion, HCV genotype 1, high HOMA, and low CD4+/µL were associated with high serum levels of sFas and sFasL, which indicate higher levels of inflammation and, possibly, increased cardiovascular risk. Moreover, response to HCV antiviral therapy is known to reduce inflammation.

Comparison of transient elastography and liver biopsy for the assessment of liver fibrosis in HIV/hepatitis C virus-coinfected patients and correlation with noninvasive serum markers.

Transient elastography (FibroScan) is a novel, rapid and noninvasive technique to assess liver fibrosis. Our objective was to compare transient elastography (TE) and other noninvasive serum indexes as alternatives to liver biopsy in HIV/hepatitis C virus (HCV)-coinfected patients. The fibrosis stage (METAVIR Score), TE, the aspartate aminotransferase-to-platelet ratio index, the Forns fibrosis index, FIB-4 and HGM-2 indexes were assessed in 100 patients between January 2007 and January 2008. The diagnostic values were compared by calculating the area under the receiver operating characteristic curves (AUROCs). Using TE, the AUROC (95% CI) of liver stiffness was 0.80 (0.72-0.89) when discriminating between F 2, 0.93 (0.85-1.00) when discriminating between F 3 and 0.99 (0.97-1.00) when discriminating between F or= 3, the AUROCs of TE were significantly higher than those obtained with the other four noninvasive indexes. Based on receiver operating characteristic curves, three cutoff values were chosen to identify F or= 3 (>or=11 kPa) and F4 (>or=14 kPa). Using these best cutoff scores, the negative predictive value and positive predictive value were 81.1% and 70.2% for the diagnosis of F or= 3 and 100% and 57.1% for the diagnosis of F4. Thus, Transient elastography accurately predicted liver fibrosis and outperformed other simple noninvasive indexes in HIV/HCV-coinfected patients. Our data suggest that TE is a helpful tool for guiding therapeutic decisions in clinical practice.

CD81 expression in peripheral blood lymphocytes before and after treatment with interferon and ribavirin in HIV/HCV coinfected patients.

BACKGROUND: CD81 is expressed on lymphocytes and confers HCV viral infectivity support. The aim of our study was to quantify CD81 expression in peripheral blood B- and T-cells of HCV/HIV-coinfected patients and healthy subjects to examine its association with several HCV virological characteristics and the therapeutic responsiveness to HCV antiviral treatment. METHODS: We carried out a cross-sectional study on 122 naïve patients. For a duration of 48 weeks, 24 out of 122 patients underwent HCV antiviral therapy with interferon (IFN)-alpha and ribavirin. T- and B-cell subsets were analysed by flow cytometry. RESULTS: We found that HIV/HCV coinfected patients with HCV-RNA > or =850 000 IU/mL had lower values of %CD19+CD81-CD62L+ and %CD19+CD62L+; and higher values of CD19+CD81+CD62L- and CD19+CD81+ percentages and absolute counts than patients with HCV-RNA <850 000 IU/mL. Similarly, HIV/HCV coinfected patients with the genotype 1 had lower values of %CD19+CD81-CD62L+ and higher values of CD3+CD81+CD62L- and CD3+CD81+ percentages and absolute counts than patients without genotype 1. Moreover, we found that HIV/HCV coinfected patients had higher values of %CD19+HLA-DR+CD25+, %CD19+CD40+CD25+ and %CD19+CD25+ than healthy control patients. When we studied the B- and T-cell subset kinetics of 24 HIV/HCV coinfected patients on HCV antiviral therapy, we found a significant decrease in CD3+CD81+and CD3+CD81+CD62L- subsets and a significant increase in CD3+CD62L+ and CD3+CD81+CD62L+ percentages and absolute counts, but the variation in these markers disappeared several months after stopping the treatment. CONCLUSIONS: We observed a different pattern of CD81 T-cell and B-cell levels in naïve HIV/HCV coinfected patients according to HCV virological status and their subsequent variations during HCV antiviral treatment. CD81 expression might influence HCV pathogenesis and response to HCV antiviral treatment.

Diagnosis of advanced fibrosis in HIV and hepatitis C virus-coinfected patients via a new noninvasive index: the HGM-3 index.

BACKGROUND: Noninvasive tests are increasingly being used for the assessment of liver fibrosis. We aimed to develop a serum index for the identification of advanced fibrosis (F>or=3) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: We carried out a cross-sectional study on a group of 195 patients comprised of an estimation group (EG; n=127) and a validation group (VG; n=68) who all underwent liver biopsy and had not received previous interferon therapy. Liver fibrosis was estimated using the METAVIR score. We developed a new serum index (HGM-3) dependent on levels of platelets, alkaline phosphatase, hepatic growth factor, tissue inhibitor of metalloproteinase-1 and hyaluronic acid. RESULTS: In the EG, the area under the receiver operating characteristic curve (AUC-ROC) of HGM-3 for identification of F>or=3 was 0.939 [95% confidence interval (CI) 0.899, 0.979] which was significantly higher than the AUC-ROC of the HGM-2, FIB-4, aspartate aminotransferase to platelet ratio (APRI) and Forns' indexes. With HGM-3 <0.135 for F<3, 57 patients were correctly identified and two patients were misclassified. We found the presence of F<3 with 96.6% certainty. The negative likelihood ratio (LR) was <0.1 and the diagnostic odds ratio (DOR) was >40. With HGM-3 >0.570 in the EG for F>or=3, 31 patients were correctly identified, and five patients were misclassified. We found the presence of F>or=3 with 86.1% certainty. The positive LR was >12 and the DOR was >40. For the VG, the diagnostic accuracy values were similar to the values for the EG. CONCLUSIONS: HGM-3 appears to be an accurate noninvasive method for the diagnosis of bridging fibrosis and cirrhosis in HIV/HCV-coinfected patients.

The relationship between antiretroviral prescription patterns and treatment guidelines in treatment-naïve HIV-1-infected patients.

BACKGROUND: Reports have shown that the publication of practice guidelines does not guarantee their use in clinical practice. The objective of this study was to evaluate the agreement between antiretroviral treatments (ARTs) prescribed in clinical practice and the recommendations in published guidelines. METHODS: A retrospective cohort study was carried out in ART-naïve adults of the Spanish Asociacion Medica Vach de Estudios Multicentricos (VACH) Cohort for the period from 2003 to 2006. RESULTS: A total of 945 patients initiated ART. Of these patients, 12.3% had a CD4 cell count above 350 cells/microL. A 'nonrecommended' antiretroviral regimen was prescribed to 5.3, 5.1 and 7.8% of patients with CD4 counts <200, 200-350 and >350 cells/microL, respectively. Multivariate analyses demonstrated that only a higher viral load was associated with the selection of a combination treatment that was recommended by the guidelines. CONCLUSIONS: Most patients were prescribed initial treatments in agreement with the recommendations. Appropriate routine data collection in databases can be used to evaluate the level of antiretroviral guideline compliance. We propose that routine evaluations of the guidelines must be part of quality assessment to improve medical care.

[Urinary levels of B-type natriuretic peptide (BNP) and ventricular systolic dysfunction in heart failure patients]. / Niveles urinarios de péptido natriurético tipo B (BNP) y disfunción ventricular sistólica en pacientes con insuficiencia cardiaca.

BACKGROUND: It was aimed to compare urine B-type natriuretic peptide (BNP) according to left ventricular systolic dysfunction and to investigate its diagnostic value in heart failure (HF) patients. MATERIAL AND METHODS: A total of 90 HF outpatients (61 men, age 66 +/- 12) and 30 age- and gender-matched controls were studied. RESULTS: An increase in urine BNP was observed in patients with EF 40% (p < 0.0001), and controls (p < 0.0001). Significant correlations between urinary BNP and left ventricular functional parameters were obtained. A multivariate regression analysis was performed and the best model associated with urine BNP included plasma BNP (p < 0.0001), EF (p = 0.02) and LV volume indexes (p < 0.0001). The ROC for detection of EF

Niveles urinarios de péptido natriurético tipo B (BNP) y disfunción ventricular sistólica en pacientes con insuficiencia cardiaca / Urinary levels of B-type natriuretic peptide (BNP) and ventricular systolic dysfunction in heart failure patients

Introducción. Comparar niveles de péptido urinario tipo B (BNP) en orina según la presenciade disfunción sistólica ventricular izquierda e investigar su valor diagnóstico enpacientes con insuficiencia cardiaca (IC).Material y métodos. Hemos estudiado a 90 pacientes ambulatorios con IC (61 hombres,edad 66 ± 12) y 30 sujetos control apareados por edad y género.Resultados. Se encontró un aumento en los niveles urinarios de BNP en los pacientes con fracciónde eyección (FE) <= 40% comparados con los de FE > 40% (p < 0,0001) y con los controles(p < 0,0001). Se obtuvieron correlaciones signifi cativas entre los niveles urinarios de BNP ylos parámetros funcionales del ventrículo izquierdo. Se realizó un análisis multivariado y elmejor modelo asociado con los niveles urinarios de BNP incluyó a los niveles de BNP en plasma(p < 0,0001), FE (p = 0,02) y volúmenes del ventrículo izquierdo (p < 0,0001). La curvaROC para la detección de FE <= 40% usando BNP urinario mostró un área bajo la curva de0,74 ± 0,05, (p < 0,0001). A partir de la curva ROC, el punto óptimo de corte (2,30 pg/ml)tuvo una sensibilidad del 60% y una especifi cidad del 90%. Finalmente, se realizó unaregresión binaria logística para la detección de FE <= 40%, y los niveles urinarios de BNPmostraron un buen valor predictivo con una odds-ratio de 21.Discusión. Los niveles urinarios de BNP se correlacionan con los parámetros funcionalesdel ventrículo izquierdo, demostrando que este marcador biológico es útil para el diagnósticode la disfunción ventricular izquierda en pacientes con insufi ciencia cardiaca(AU)

Background. It was aimed to compare urine B-type natriuretic peptide (BNP) according toleft ventricular systolic dysfunction and to investigate its diagnostic value in heart failure(HF) patients.Material and methods. A total of 90 HF outpatients (61 men, age 66 ± 12) and 30 age- andgender-matched controls were studied.Results. An increase in urine BNP was observed in patients with EF<= 40% compared toEF> 40% (p < 0.0001), and controls (p < 0.0001). Signifi cant correlations between urinaryBNP and left ventricular functional parameters were obtained. A multivariate regressionanalysis was performed and the best model associated with urine BNP included plasmaBNP (p < 0.0001), EF (p = 0.02) and LV volume indexes (p < 0.0001). The ROC fordetection of EF <= 40% using urine BNP levels showed an area under the curve of 0.74 ±0.05, (p < 0.0001). From the ROC curve, the optimal cut-off value (2.30 ng/l) had a 60%sensitivity and 90% specifi city. Finally, we performed a binary logistic regression fordetection of EF <= 40%, and urine BNP was shown to be a strong predictor with an oddsratioof 21.Discussion. Urine BNP levels correlated with left ventricular functional parameters. Thisbiomarker is a useful tool for detecting and diagnosing left ventricular systolic dysfunctionin heart failure(AU)

Amlodipine reduces predicted risk of coronary heart disease in high-risk patients with hypertension in Spain (The CORONARIA Study).

We evaluated the efficacy and safety of amlodipine besylate alone or in combination with other antihypertensive agents in high-risk hypertensive patients in Spanish primary care. In this 1-year, open-label, prospective cohort study, 7468 patients were treated with amlodipine 5 - 10 mg as a monotherapy or as an add-on therapy to attain blood pressure control (target of < 140/90 mmHg or, in patients with conditions such as diabetes or chronic kidney disease, < 130/85 mmHg). At 12 months, the primary outcome (change from baseline in predicted 10-year coronary heart disease risk) was -8.6%, down from 24.7% at baseline (relative risk reduction, 31.6%). Change in blood pressure from baseline (162.5/95.3 mmHg) was -26.7/-14.6 mmHg, and 38.6% of patients achieved their blood pressure target. In summary, significant reductions in predicted coronary heart disease risk and blood pressure were observed with amlodipine both as a monotherapy and as an add-on therapy. Amlodipine was well tolerated and compliance with treatment was good.

Residual platelet thromboxane A2 and prothrombotic effects of erythrocytes are important determinants of aspirin resistance in patients with vascular disease.

BACKGROUND: Permanent inactivation of cyclooxygenase-1 and inhibition of platelet thromboxane A(2) (TxA(2)) constitute the main mechanisms underlying the prevention of vascular disease by aspirin. METHODS AND RESULTS: We studied platelet TxA(2) synthesis and its impact on platelet reactivity and platelet-erythrocyte [platelet-rich plasma (PRP)-RBC] interactions in 533 aspirin-treated patients with vascular disease. Seventy aspirin-free and 16 aspirin-treated normal subjects were evaluated as controls. Collagen (1 mug mL(-1))-induced platelet activation ((14)C-5HT release) and recruitment (proaggregatory activity of cell-free releasates from activated platelets) were assessed in PRP, PRP + RBC, and whole blood (WB). TxA(2) was quantified in releasates from WB. Aspirin inhibited TxA(2) synthesis and platelet function in all patients, but to different degrees. Forty-two patients (8%) displayed partial (<95%) inhibition of TxA(2) relative to that of aspirin-free controls. They produced >3.5 ng mL(-1) TxA(2) and had higher platelet reactivity than 491 patients who had undetectable TxA(2) or produced residual TxA(2) (R-TxA(2);

Pathology of stage I versus stage III ovarian carcinoma with implications for pathogenesis and screening.

The progression of ovarian carcinoma from stage I when it is confined to the ovaries and curable to disseminated abdominal disease, which is usually fatal, is poorly understood. An accurate understanding of this process is fundamental to designing, testing, and implementing an effective screening program for ovarian cancer. Pathologic features of the primary ovarian tumors in 41 FIGO stage I ovarian carcinomas were compared with those in 40 stage III carcinomas. The primary ovarian tumors in stage I cases, when compared with stage III, respectively, were significantly larger (15.4 versus 9.8 cm), were less frequently bilateral (12% versus 75%), more frequently contained a noninvasive component (88% versus 30%), had a higher proportion of a noninvasive component (42% versus 8%), and were more often nonserous (83% versus 20%) (P < 0.001 for all five comparisons). There are significant pathologic differences between the primary ovarian tumors in stage I and III ovarian carcinomas that are very difficult to explain by a simple temporal progression. These findings along with the growing body of literature suggest that early- and advanced-stage ovarian cancers are in many instances biologically different entities. This knowledge may have significant implications for our understanding of the biology of early- and advanced-stage ovarian cancer and therefore on the development of screening strategies for ovarian cancer.

Identification of liver fibrosis in HIV/HCV-coinfected patients using a simple predictive model based on routine laboratory data.

We constructed noninvasive models to predict significant fibrosis (F > or = 2) and advanced fibrosis (F > or = 3) among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients, naïve for anti-HCV treatment. A total of 296 patients with liver biopsy were randomly assigned to an estimation group (EG = 226; 70%) and a validation group (VG = 70; 30%). We developed the Hospital Gregorio Marañón (HGM)-1 index, based on platelet count, aspartate aminotransferase (AST) and glucose, to predict F > or = 2 and the HGM-2 index, based on platelet count, international normalized ratio, alkaline phosphatase and AST to predict F > or = 3. The area under the receiver operating characteristic curves (AUROCs) of the HGM-1 index for the EG and the VG were 0.807 and 0.712 respectively. The AUROCs of the HGM-2 index for the EG and the VG were 0.844 and 0.815 respectively. With the HGM-1 index applied to the VG, using best cutoff scores, the negative predictive value (NPV) to exclude F > or = 2 was 54.5% and the positive predictive value (PPV) to confirm F > or = 2 was 93.3%. With the HGM-2 index applied to the VG, using best cutoff scores, the NPV to exclude F > or = 3 was 92.3, and the PPV to confirm F > or = 3 was 64.3%. Thus, HGM-2 accurately predicted F > or = 3 among HIV/HCV-coinfected patients. HGM-1 was less accurate at predicting F > or = 2.

Hematologic changes after splenectomy for cytoreduction: implications for predicting infection and effects on chemotherapy.

Postsplenectomy leukocytosis and thrombocytosis are common findings in trauma patients. The intent of this study is to describe postsplenectomy hematologic changes in gynecological oncology surgery and subsequent chemotherapy. We performed a retrospective record review of gynecological oncology patients at our institutions. Postsurgical hematologic changes, infectious morbidity, and pre- and post-chemotherapy hematologic changes were noted. Data were analyzed using repeated measures analysis of variance. We identified 27 patients who underwent cytoreductive surgery with splenectomy. Thirteen patients with splenectomy had postoperative chemotherapy data available, and we matched these patients with 13 control patients who underwent cytoreduction surgery without splenectomy and postoperative chemotherapy. Nine of the 27 splenectomy patients had documented infectious morbidity. There was a significant difference in postoperative platelet counts between the infected and the noninfected splenectomy patients (P= 0.037), and a significant difference between splenectomy and control patients for white blood cell (WBC) counts (P = 0.007). Patients with splenectomy had higher precycle WBC, absolute neutrophil count (ANC), platelet counts, and higher postcycle nadir levels in all cycles compared to control patients. There was a significant overall difference between splenectomy patients and controls with regard to WBC (P = 0.001), ANC (P = 0.005), and platelet counts (P = 0.016) during chemotherapy cycles. Median postchemotherapy nadir WBC was 4.4 (range: 3.4-4.8) for the splenectomy group versus 2.8 (range: 2.5-3.0) for the control group. Median postchemotherapy nadir ANC was 1800 (range: 1320-2450) for the splenectomy group and 1001 (range: 864-1064) for the control group. Median postchemotherapy nadir platelet count was 222 (range: 181-277) for the splenectomy patients and 169 (range 164-215) for the control patients. In conclusion, the patients who undergo splenectomy as part of cytoreductive surgeries have a statistically significant leukocytosis and insignificant thrombocytosis relative to the control patients. Leukocytosis alone is not an accurate indicator of infection. Splenectomy is not associated with an increased risk of chemotherapy-related neutropenia and thrombocytopenia.

Utilización de células madre en terapia regenerativa Cardíaca / No disponible

La posibilidad de utilizar células madre en el tratamiento de diversas enfermedades humanas como la diabetes, la enfermedad de Parkinson, la cardiopatía isquémica constituye uno de los retos mas importantes de la medicina moderna. Sin embargo, antes de que los resultados de los estudios con células madre se traduzcan clínicamente existen múltiples problemas que deben ser resueltos. A continuación trataremos de exponer algunos conceptos relacionados con las células madre y su potencial, centrándonos principalmente en las células madre adultas tal como han sido recientemente descritas por el grupo de Catherine Verfaillie. Además presentaremos resultados de alguno de los primeros estudios clínicos realizados con células madre adultas como forma de terapia regenerativa cardíaca. En dichos trabajos se han empleado células madre de músculo (células satélite) autólogas en pacientes con infarto de miocardio, inyectándose directamente dichas células en la periferia de la cicatriz secundaria al infarto (AU)

One of the most important challenges in modern medicine is the use of stem cells for the treatment of human disease such as diabetes, Parkinson´s disease or isquemic cardiomyopathy. A number of problems need to be solved before stem cells can be applied clinically. In this paper we will review some concepts related to the potential of stem cells, focusing on adult stem cells as they have recently been described by the group of Catherine Verfaillie. We will also present our initial clinical results using adult stem cells for cardiac regenerative therapy. In the studies mentioned above, autologous muscle stem cells (satelite cells) were infused directly in the periphery of the scar tissue of the infarct. We describe the technique for ex vivo expansion and purification of muscle stem cells (AU)

Inflammatory reactions in progressive multifocal leukoencephalopathy after highly active antiretroviral therapy.

Three patients with progressive multifocal leukoencephalopathy (PML) treated with highly active antiretroviral therapy (HAART) worsened clinically and radiologically. At the time of deterioration all three had reduced HIV viraemia and increased CD4 cell counts. Brain biopsy in all three disclosed PML and marked perivascular lymphoplasmacytic infiltration. We reviewed the slides of 28 brain biopsies diagnostic of PML. Inflammatory changes were observed in four out of nine patients on HAART and in one out of 19 patients not on HAART.

Nelfinavir plus nevirapine plus two NRTIS as salvage therapy for HIV-infected patients receiving long-term antiretroviral treatment.

PURPOSE: To evaluate a rescue therapy involving nevirapine plus nelfinavir plus two nucleoside reverse transcriptase inhibitors (NRTIs) in patients with prior extensive antiretroviral therapy (AT) including protease inhibitors (PIs) but not nonnucleoside reverse transcriptase inhibitors (NNRTIs). METHOD: Patients with failing regimens were prospectively enrolled. According to genotypic profile at baseline, two groups were identified: a highly resistant (HR) group, which included strains resistant to PI and NRTI, and a moderate nonresistant group (MR), which showed resistance only to PI or NRTI or no resistance. RESULTS: Twenty-two individuals were included. Average time of AT prior to enrollment was 3.7 years (range 1.4-7.6), median viral load 4.92 log(10) (interquartile range [IQR] 1.63 log(10)), and median CD4 cell count 64 cells/microL (IQR 94). After 16 weeks of treatment, seven patients (31%) achieved virological response, five of them (22.7%) with <500 c/mL (bDNA). Fourteen patients were studied for resistance. The HR group showed a poorer response than the MR group (0 vs. 7 responses; p =.034). CONCLUSION: We found a virological response in 31% of our patients, and mainly in those of the MR group some presented previous intolerance. These two factors probably reflect the number of drugs included in the rescue therapy to which the patient is sensitive. Treatment history as well as genotypic resistance assays are useful in identifying patients with the best chance of responding.