A propensity score-weighted study comparing a two- versus four-weekly pegylated liposomal doxorubicin regimen in metastatic breast cancer.

PURPOSE: A 4-weekly schedule of pegylated liposomal doxorubicin (PLD) has been approved for the treatment of metastatic breast cancer (MBC). Phase II trials have suggested interest in a 2-weekly regimen. This study aimed to compare the efficacy and safety of these two schedules. METHODS: Data from MBC patients treated with PLD between 2011 and 2021 were retrospectively collected. The objective was to demonstrate the noninferiority of the 2-weekly versus the 4-weekly schedule in terms of 6-month progression-free survival (PFS). The prespecified noninferiority margin was calculated as 1.20. A propensity score to receive either schedule was estimated using a gradient boosting algorithm. Survival analyses using Cox regression models weighted by the propensity score were performed to compare the schedules. RESULTS: Among the 192 patients included, 96 (50%) underwent each schedule. The median number of previous systemic therapies was 4 (IQR, 3 to 6). Anthracyclines were previously given in early breast cancer in 63.9% of patients. The median follow-up was 10.0 months (IQR, 5.0 to 20.1). A comparable distribution of adverse events was observed. The median PFS was 3.2 months (95% CI, 2.9 to 3.9), and the median overall survival was 12.1 months (95% CI, 10.8 to 14.9). The weighted hazard ratio for PFS was 1.12 (90% CI, 0.82 to 1.54), including the noninferiority boundaries. CONCLUSION: PLD appeared to be a well-tolerated drug in this heavily pretreated MBC population. The efficacy and safety of the 2-weekly schedule did not provide any advantage, suggesting no interest in changing the registered regimen.

Medullary thyroid cancer outcomes in patients with undetectable versus normalized postoperative calcitonin levels.

BACKGROUND: Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors in medullary thyroid cancer (MTC). This study aimed to evaluate progression-free survival and recurrence rates of MTC associated with undetectable compared with normalized serum Ct levels after surgery. METHODS: This retrospective observational study included patients operated for MTC at the Digestive and Endocrine Surgery Department of Lyon Sud Hospital Centre between 2000 and 2019. Clinical and pathological factors were correlated with postoperative Ct concentrations. Undetectable and normalized Ct concentrations were defined as below 2 pg/ml and 2-10 pg/ml respectively. RESULTS: Overall, 176 patients were treated for MTC, and 127 were considered biochemically cured after surgery. Of these, 24 and 103 had normalized and undetectable Ct concentrations respectively. Patients with Ct level normalization had a 25 per cent risk of disease recurrence, compared with 3 per cent in patients with undetectable Ct levels after surgery. The presence of metastasis in two or more compartments was predictive of failure to achieve undetectable Ct concentrations after surgery and an increased risk of recurrence. CONCLUSION: Among patients with biochemically cured MTC, those with undetectable or normalized Ct concentrations after surgery had different risks of recurrence. Simply assessing postoperative Ct normalization can be falsely reassuring, and long-term follow-up is needed. LAY SUMMARY: Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors for medullary thyroid cancer outcomes; however, the significance of postoperative Ct levels remains controversial. This study evaluated the differences between normal and undetectable postoperative Ct levels in patients who had undergone surgical treatment for medullary thyroid cancer. Patients who experienced postoperative Ct level normalization had a higher risk of disease recurrence than those with undetectable Ct levels after surgery.

Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors for medullary thyroid cancer outcomes; however, the significance of postoperative Ct levels remains controversial. This study evaluated the differences between normal and undetectable postoperative Ct levels in patients who had undergone surgical treatment for medullary thyroid cancer. Patients who experienced postoperative Ct level normalization had a higher risk of disease recurrence than those with undetectable Ct levels after surgery.

Niveles de Interferón Tipo I en pacientes con Lupus Eritematoso Sistémico / Type I interferon levels in patients with systemic lupus erythematosus

Introducción: El interferón (IFN) tipo I es una citoquina que juega un rol fundamental en la patogenia del Lupus Eritematoso Sistémico (LES). Diferentes niveles de esta citoquina podrían explicar la heterogeneidad de esta patología y ser útil para evaluar la actividad de la misma. Objetivos: Determinar los niveles de IFN tipo I sérico en pacientes con LES y evaluar su utilidad como biomarcador de actividad. Material y Métodos: 16 pacientes con LES (ACR 1997) y 16 controles. Métodos: Actividad de la enfermedad (SLEDAI-2K), daño orgánico (SLICC), IFN tipo I (HEK-Blue-IFNα/β), anticuerpos anti-DNAdc (Inmunofluorescencia Indirecta), anticuerpos anti-ENA (ELISA), C3-C4 (Inmunoturbidimetría). Estadística: InfoStat/Instat/MedCalc. Valores de p<0,05 fueron considerados estadísticamente significativos. Resultados: Se observó un aumento de la concentración de IFN en el grupo LES con respecto al control (p<0,05). Los pacientes con valores de IFN superiores al punto de corte, se asociaron con la presencia de anticuerpos anti-DNAdc (OR:13,33; p<0,05). Pacientes con hipocomplementemia y aquellos con puntaje de SLEDAI-2K mayor a 8 presentaron mayores niveles de IFN comparados con pacientes con complemento normal y menor puntaje de índice, respectivamente (p<0,05). Conclusiones: Estos resultados sugieren la importancia que podría tener la determinación de IFN tipo I para el monitoreo de la actividad del LES.

Introduction: Type I interferon (IFN) is a cytokine that plays a fundamental role in the pathogenesis of Systemic Lupus Erythematosus (SLE). Different levels of this cytokine could explain the heterogeneity of this pathology and be useful to evaluate its activity. Objectives: To determine the serum type I IFN levels in patients with SLE and evaluate its usefulness as a biomarker of activity. Material and Method: 16 patients with SLE (ACR 1997) and 16 controls. Methods: Disease activity (SLEDAI-2K), organ damage (SLICC), type I IFN (HEK-Blue-IFNα/β), anti-dsDNA antibodies (Indirect Immunofluorescence), anti-ENA antibodies (ELISA), C3-C4 (Immunoturbidimetry). Statistics: InfoStat/Instat/MedCalc. P values <0.05 were statistically significant. Results: An increase in IFN concentration was observed in the SLE group respect to the control (p <0.05). Patients with IFN values above the cut-off point were associated with the presence of anti-dsDNA antibodies (OR: 13.33; p<0.05). Hypocomplementemic patients and those with a SLEDAI-2K score greater than 8 had higher IFN levels compared to patients with normal complement and a lower index score, respectively (p<0.05). Conclusions: These results suggest the importance that the determination of IFN type I could have for the monitoring of SLE activity.

Autofluorescence pattern of parathyroid adenomas.

BACKGROUND: Primary hyperparathyroidism (pHPT) is a common endocrine pathology, and it is due to a single parathyroid adenoma in 80-85 per cent of patients. Near-infrared autofluorescence (NIRAF) has recently been used in endocrine surgery to help in the identification of parathyroid tissue, although there is currently no consensus on whether this technique can differentiate between normal and abnormal parathyroid glands. The aim of this study was to describe the autofluorescence pattern of parathyroid adenoma in pHPT. METHODS: Between January and June 2019, patients with pHPT who underwent surgical treatment for parathyroid adenoma were enrolled. Parathyroid autofluorescence was measured. RESULTS: Twenty-three patients with histologically confirmed parathyroid adenomas were included. Parathyroid adenomas showed a heterogeneous fluorescence pattern, and a well defined autofluorescent 'cap' region was observed in 17 of 23 specimens. This region was on average 28 per cent more fluorescent than the rest of the adenoma, and corresponded to a rim of normal histological parathyroid tissue (sensitivity and specificity 88 and 67 per cent respectively). After resection, all patients were treated successfully, with normal postoperative values of calcium and parathyroid hormone documented. CONCLUSION: Parathyroid adenomas show a heterogeneous autofluorescence pattern. Using NIRAF imaging, the majority of specimens showed a well defined autofluorescent portion corresponding to a rim of normal parathyroid tissue. Further studies should be conducted to validate these findings.

Efecto de la edad en la seroprevalencia de anticuerpos IgG antivirus de Hepatitis A en el personal de salud

RESUMEN Introducción: La incorporación de la vacuna de la Hepatitis A (HA) en el año 2005 y las mejoras en las condiciones sanitarias y socio-económicas disminuyeron la endemicidad de dicha enfermedad en nuestro país, pero generaron un corrimiento etario de la población vulnerable. El equipo de salud pertenece al grupo de riesgo ocupacional con recomendación de vacunación. Nuestro objetivo fue analizar el efecto de la edad sobre los niveles de anticuerpos IgG anti virus de la HA (VHA) en un grupo de trabajadores del ámbito sanitario del Hospital Córdoba. Materiales y Métodos: Se determinó IgG anti VHA por quimioluminiscencia. Criterios de exclusión: haber padecido HA y/o haber recibido la vacuna. Se realizó una breve encuesta para obtener datos epidemiológicos. Para el análisis estadístico se utilizó el test t-Student, una curva ROC y la prueba Chi-cuadrado. Valores de p<0,05 fueron considerados estadísticamente significativos. Resultados: El grupo en estudio estuvo constituido por 90 profesionales entre 25-69 años. La seroprevalencia de IgG antiVHA fue 62,2%. Se detectaron 34 personas seronegativas con una edad promedio de 37.6±10.6, que fue significativamente menor a la del grupo seropositivo 45.3±10.8 años (p=0.0014). El punto de corte etario fue 41 años (p=0,0001; ABC=0,709; S=60,7%; E=73,5%). Los menores de 41 años presentaron una asociación estadísticamente significativa con IgG anti VHA negativa, OR=3.57. Conclusiones: Los profesionales menores de 41 años se asocian a serología anti VHA negativa. Debería evaluarse la indicación de realizar control serológico y vacunar a todo el personal que no presente anticuerpos protectivos al ingreso hospitalario

ABSTRACT Introduction: The incorporation of the hepatitis A (HA) vaccine in 2005 and the improvements in sanitary and socioeconomic conditions reduced the endemicity of this disease in our country, but generated an age shift of the vulnerable population. The health personnel belongs to the occupational risk group with recommendation of vaccination. Our aim was analyze the effect of age on the levels of IgG antibodies against hepatitis A virus (HAV) in a group of health workers at the Hospital Córdoba. Materials and Methods: HAV-specific IgG antibodies was determined by chemiluminescence. Exclusion criteria: to have suffered HA and/or received HA vaccine. A brief survey was made to obtain epidemiological data. We used the t-Student test, ROC curve and Chi-square test for statistical analysis. Values of p <0.05 were considered statistically significant. Results: The study group was formed by 90 professionals between 25-69 years. The seroprevalence of HAV-specific IgG antibodies was 62.2%. 34 seronegative persons were detected with a mean age of 37.6±10.6, which was significantly lower than the mean age of the seropositive group 45.3±10.8 years (p=0.0014). The age cut-off was 41 years (p = 0.0001; ABC = 0.709; S = 60.7%; E = 73.5%). Individuals under the age of 41 had a statistically significant association with negative HAV-IgG, OR = 3.57. Conclusions: Professionals under 41 years are associated with negative HAV IgG antibodies values. The indication to perform serological control and vaccinate any professionals who do not present protective antibodies at the time of hospital admission should be evaluated.

EVALUACIÓN DE LA EXACTITUD DIAGNÓSTICA DE ANTICUERPOS ANTIGLIADINA DEAMINADA IgG (a-DGP) EN ENFERMEDAD CELÍACA

Introducción: Si bien la biopsia intestinal es la técnica-patrón para el diagnóstico de la Enfermedad Celíaca (EC), los ensayos serológicos son un importante complemento en el screening, diagnóstico y seguimiento de la misma. Estos son anticuerpos anti-Transglutaminasa IgA (aTgt), anticuerpos anti-endomisio IgA (EMA) y anticuerpos anti-péptidos de gliadina-deaminados IgG (a-DGP). Nuestros objetivos fueron evaluar la exactitud diagnóstica de a-DGP en pacientes adultos con diagnóstico de EC que concurrieron al Hospital Córdoba y comparar la concordancia de a-DGP con aTgt y EMA. Materiales y métodos: Se realizó un estudio experimental en el Hospital Córdoba. Se analizaron sueros conservados a - 20° C, de 54 pacientes (Marzo de 2015 a Diciembre 2017) sometidos a biopsia intestinal. Las muestras de tejido permitieron determinar los siguientes grupos:´ Grupo Enfermedad Celíaca (GEC): 25 pacientes con biopsia positiva para EC, de acuerdo a la clasificación de Marsh. Grupo Control (GC): 29 pacientes con biopsia negativa para EC. Se determinaron niveles de: a-DGP y aTgt por ELISA comercial, EMA por Inmunofluorescencia indirecta e Ig A sérica por inmunoturbidimetría. Análisis estadísticos de los datos: Se utilizaron los programas estadísticos "InfoStat" y "MedCalc" 10.2.0.0. La concordancia se determinó por el índice kappa (κ). Un valor de p <0,05 fue considerado estadísticamente significativo. Resultados: El valor de corte para a-DGP fue de 15,4 U/ml. La exactitud diagnostica para el título de corte fue de 94,44%. El valor de corte para aTgt fue de 9,3 U/ml. La exactitud diagnostica fue de 92,59 %. La concordancia entre a-DGP y aTgt fue sustancial (κ= 0.740) y casi perfecto entre a-DGP y EMA (κ=0,851). Conclusiones: El ELISA para a-DGP demostró una elevada exactitud diagnóstica. Se observó una mejor concordancia de a-DGP con EMA que con aTgt. Los resultados obtenidos confirman el potencial clínico de este marcador serológico como complemento diagnóstico de EC.

Introduction: Although intestinal biopsy is the standard technique for the diagnosis of Celiac Disease (CD), serological tests are an important complement in the screening, diagnosis and follow-up of the same. These are antibodies IgA to transglutaminase antibodies (aTgt), Ig A antibodies to endomysium (EMA) and antibodies to deamidated gliadin peptides (a-DGP). Our objectives were to evaluate the diagnostic accuracy of a-DGP in adult patients with a diagnosis of CD who attended the Córdoba Hospital and compare the concordance of a-DGP with aTgt and EMA. Materials and methods: An experimental study was carried out at the Hospital Córdoba. Serums conserved at -20 ° C were analyzed, from 54 patients (March 2015 to December 2017) submitted to intestinal biopsy. The tissue samples allowed to determine the following groups: Celiac Disease Group (GEC): 25 patients with a positive biopsy for CD, according to the Marsh classification. Control Group (GC): 29 patients with negative biopsy for CD. Levels of: a-DGP and aTgt were determined by commercial ELISA, EMA by indirect Immunofluorescence and serum IgA by immunoturbidimetry. Statistical analysis of the data: Statistical programs "InfoStat" and "MedCalc" 10.2.0.0 were used. The concordance was determined by the kappa index (κ). A value of p <0.05 was considered statistically significant. Results: The cut-off value for a-DGP was 15.4 U / ml. The diagnostic accuracy for the cutoff title was 94.44%. The cut-off value for aTgt was 9.3 U / ml. The diagnostic accuracy was 92.59%. The agreement between a-DGP and aTgt was substantial (κ = 0.740) and almost perfect between a-DGP and EMA (κ = 0.851). Conclusions: The ELISA for a-DGP demonstrated a high diagnostic accuracy. A better concordance of a-DGP with EMA was observed than with aTgt. The results obtained confirm the clinical potential of this serological marker as a diagnostic complement of CD.

[Clinical usefulness of Beta2microglobulin in patients with Primary Sjögren Syndrome]. / Utilidad clínica de Beta2microglobulina en pacientes con Síndrome de Sjögren Primario.

The extraglandular manifestations and lymphoproliferative disorders are complications in pSS. There are few serological markers that they are useful in these conditions. OBJETIVES: to evaluate the usefulness of the ß2microglobulin level in patients with pSS and its relation to extra glands manifestations , lymphoproliferative disorders and the presence of Rheumatoid factor (RF), serum immunoglobulins (Igs), and C3 and C4 levels. MATERIAL AND METHODS: we retrospectively studied patients with pSS , OAD and healthy controls . Ig G, Ig A and Ig M levels, serum complement C3 and C4 and RF were performed by immunoturbidimetry, and ß2microglobulin protein by the ELISA technique in all patients. RESULTS: 19 patients with pSS (Group SSp), 28 patients with other autoimme diseases diferent from pSS (Group PAD) and 24 healthy controls (Group C).There was an signifcant increase of ß2m values in Groups SS and OAD vs Group C (6.19 mg/dl vs. 2.53 mg/dl p<0.001) and (4.38 mg/dl vs. 2.53 mg/dl p<0.01). On the other hand, mean ß2m levels in Group SS were higher than in Group OAD (6.19 vs. 4.38 mg/dl p<0.01).There was not a relationship between ß2m level and Ig G, A , M ,complement levels and the presence of RF. CONCLUSION: ß2m can discriminate patients with pSS from those with other autoimmune diseases and healthy subjects. Increased ß2m level in pattients with pSS could reflect hyperactivation of B cells and it could be a potential marker associated with extraglandular manifestations and cell lymphoproliferative disorders.

Las manifestaciones extranglandulares y desórdenes linfoproliferativos son complicaciones que pueden comprometer el curso benigno del Síndrome de Sjögren Primario (SSp). Existen escasos marcadores serológicos con comprobada utilidad para predecirlas y/o diagnosticarlas. Objetivos: Evaluar la utilidad de Beta2microglobulina (ß2m) en pacientes con SSp y correlacionarlos con parámetros séricos predictivos de manifestaciones extraglandulares y enfermedades linfoproliferativas (Factor Reumatoideo (FR), Inmunoglobulinas séricas (Igs), C3 y C4). Materiales y métodos: Se realizó una revisión retrospectiva de historias clínicas de pacientes que consultaron en la Unidad de Reumatología del Hospital Córdoba desde enero de 2010 a octubre 2013 y que fueron derivados a la Sección de Inmunología del Servicio de Bioquímica para la determinación de pruebas de laboratorio . Los pacientes fueron clasificados de acuerdo a los Criterios Diagnósticos de patologías autoinmunes en pacientes con diagnóstico de SSp según el Grupo Consenso Americano-Europeo, otras enfermedades autoinmunes y los controles sanos. Se estudiaron las IgG, IgA e IgM, factores del complemento C3, C4 séricos y FR por inmunoturbidimetría y ß2m por ELISA. Resultados: 19 pacientes con SSp (Grupo SSp), 28 pacientes con patologías autoinmunes distintas a SSp (Grupo PAD), y 24 controles sanos (Grupo C) fueron incluidos en este estudio. Se evidenció un aumento estadísticamente significativo de ß2m en el Grupo SSp respecto al Grupo C (6.19mg/dl vs 2.53mg/dl p<0.001) y respecto al Grupo PAD (6.19 vs 4.38mg/dl p<0.01). En el grupo SSp se observó aumento estadísticamente significativo de IgA (p<0.05) y G (p<0.001) y disminución de C4 (p<0.05) respecto al Grupo C. No se observó correlación entre ß2m y el resto de parámetros séricos determinados. Conclusión: ß2m permitió discriminar pacientes con SSp de aquellos con otras patologías autoinmunes y sujetos sanos. El aumento de ß2m en pacientes con SSp podría reflejar la hiperactivación de células B y podría ser un marcador asociado con las manifestaciones extraglandulares y desórdenes linfoproliferativos.

A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer.

BACKGROUND: Masitinib is a selective oral tyrosine-kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Patients with inoperable, chemotherapy-naïve, PDAC were randomized (1 : 1) to receive gemcitabine (1000 mg/m(2)) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic. RESULTS: Three hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl-CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the 'ACOX1' subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the 'pain' subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable. CONCLUSIONS: The present data warrant initiation of a confirmatory study that may support the use of masitinib plus gemcitabine for treatment of PDAC patients with overexpression of ACOX1 or baseline pain (VAS > 20mm). Masitinib's effect in these subgroups is also supported by biological plausibility and evidence of internal clinical validation. TRIAL REGISTRATION: ClinicalTrials.gov:NCT00789633.

DCF (docetaxel, cisplatin and 5-fluorouracil) chemotherapy is a promising treatment for recurrent advanced squamous cell anal carcinoma.

BACKGROUND: Squamous cell carcinoma of the anal canal (SCCA) is a rare disease, mostly diagnosed at early stage. After concurrent chemoradiation (CRT) with mitomycin C and 5-fluorouracil (5FU), local or metastatic recurrences occur in >20% of the patients. After treatment failure, cisplatin (CDDP)-based chemotherapy is the standard option, but complete response (CR) is a rare event and the prognosis remains poor. PATIENTS AND METHODS: Eight consecutive patients with advanced recurrent SCCA after CRT were treated with DCF regimen (docetaxel 75 mg/m(2) day 1, CDDP 75 mg/m(2) day 1 and 5FU at 750 mg/m(2)/day for 5 days every 3 weeks). Tumour samples were analysed for human papillomavirus (HPV) genotyping, as well as p16 and p53 expression. RESULTS: After a median follow-up of 41 months, the overall survival rate at 12 months was 62.5% (95% CI 22.9-86.1 months). Four patients achieved a complete remission and remain relapse-free at the time of analysis with a progression-free survival of 19, 33, 43 and 88 months. Three of these patients underwent surgery for all involved metastatic sites. For all of them, pathological CR was confirmed. DCF regimen appeared feasible in these patients previously exposed to pelvic CRT, and no grade IV toxicity occurred. All patients in complete remission had HPV-16-positive SCCA, while HPV could only be detected among 50% of the non-responding patients. Of interest, immunohistochemical study revealed a p16(+)/p53(-) phenotype in these patients, while none of non-responders expressed p16. CONCLUSION: The high level of complete and long-lasting remission among SCCA patients treated with DCF regimen supports the assessment of this strategy in prospective cohorts.

Extended-pedicle peroneal artery perforator flap in intraoral reconstruction.

The peroneal artery perforator (PNAP) flap is a good choice for reconstruction in intraoral soft-tissue rehabilitation. In this article, the authors propose the use of a modified PNAP flap with pedicle extension.

Phase II study assessing lapatinib added to letrozole in patients with progressive disease under aromatase inhibitor in metastatic breast cancer-Study BES 06.

This trial evaluated the effect of adding lapatinib to letrozole after clinical resistance to aromatase inhibitor (IA) treatment in hormone receptor-positive metastatic breast cancer. Postmenopausal women received daily letrozole plus lapatinib (1,500 mg). The primary end point was objective rate response (ORR) at week 12. Secondary objectives included time to response, duration of response, clinical benefit (CB), progression-free survival (PFS), overall survival, and safety. Twenty-four human epidermal growth factor receptor 2 (HER2)-negative patients were included with secondary resistance to IA. ORR at 12 weeks was 4 % (95 % confidence interval (CI), 0.7-20). Stable and progression diseases were reported in 25 % (95 % CI, 12-45) and 71 % (95 % CI, 51-85) of cases, respectively. At 24 weeks, the ORR increased to 8 %. CB was 21 % (95 % CI, 9-40). At a median follow-up of 27 months, median PFS was 3.4 months (95 % CI, 2.8-5.4). Grade 3 or 4 adverse events were rarely reported. No clinical cardiac toxicity was observed. Lapatinib was discontinued in two patients due to severe diarrhea. This trial was prematurely closed due to low recruitment. These preliminary results suggest that the addition of lapatinib to letrozole has a favorable safety profile and could overcome tumoral resistance to letrozole among HER2-negative tumors.

Economic impact of prescribing error prevention with computerized physician order entry of injectable antineoplastic drugs.

UNLABELLED: A cost-benefit analysis was carried out to determine the potential economic costs and benefits of pharmaceutical analysis in preventing prescribing errors for full standardized injectable antineoplastic drugs computerized physician order entry, in a pharmaceutical unit (University teaching hospital), compared with theoretical setting with no pharmaceutical analysis. The viewpoint is that of the payer or the French national Public Health Insurance system, and is limited to hospital cost (only direct medical costs related to net cost and net benefit. A decision analysis model was performed to compare two strategies: with pharmaceutical analysis (± pharmacy intervention) and without pharmaceutical analysis. RESULTS: are expressed in terms of benefit-to-cost ratio and total benefit. The robustness of the results was assessed through a series of one-way sensitivity analyses. Over 1 year, prescribing error incidence was estimated at 1.5% [1.3-1.7], i.e. 218 avoided prescribing errors. Potential avoidance of hospital stay was estimated at 419 days or 1.9 ± 0.3 days per prescribing error. Cost-benefit analysis could estimate a net benefit-to-cost ratio of 33.3 (€17.34/€0.52) and a total benefit at €16.82 per pharmaceutical analysis or €249,844 per year. The sensitivity analysis showed robustness of results. Our study shows a substantial economic benefit of pharmaceutical analysis and intervention in the prevention of prescribing errors. The clinical pharmacist adds both value and economic benefit, making it possible to avoid additional use of expensive antineoplastic drugs and hospitalization. Computerized physician order entry of antineoplastic drugs improves the relevance of clinical pharmacist interventions, expanding pharmaceutical analysis and also the role of the pharmacist.

Correlación de hallazgos serológicos y compuestos orgánicos en saliva en el Síndrome de Sjõgren / Correlation of serological findings and saliva’s organic compounds in Sjõgren’s Syndrome

Introducción: El objetivo del presente trabajo es evaluar los cambios en flujo y composición orgánica en saliva, así como la presencia de anticuerpos anti Ro/SSA y La/SSB séricos y salivales y su implicancia en el diagnóstico no invasivo del SS. Diseño del estudio: Estudio de corte transversal, de 73 pacientes distribuidos en los siguientes grupos experimentales: Síndrome de Sjõgren primario (SSp) (n = 15), SS secundario (SSs) (n = 17), boca seca y ojo seco sin Síndrome de Sjõgren (BO) (n = 20), y controles sanos (C) (n = 21). Se realizó una determinación del flujosalivalbasal y una toma de muestras de saliva para la medición de proteínas totales, IgA, urea y anticuerpos. Se determinaron anticuerpos anti Ro/SSA y La/SSB en muestras de suero y saliva. Resultados: El flujo salival en SSp, SSs, BO fue significativamente menor (p < 0,001) comparado con C. La composición salival de SS mostró modificaciones de componentes estudiados. Los anticuerpos anti Ro/SSA y anti La/SSB aparecieron con mayor frecuencia en suero y saliva en pacientes con SS en comparación con BO y C, siendo la frecuencia de positividad superior en suero en comparación con saliva. Conclusión: La determinación de anticuerpos Ro/SSA en saliva podrían ayudar a diagnosticar a pacientes con xerostomía como el Síndrome de Sjõgren.

Introduction: The aim of this study was to evaluate changes in flow andorganic composition in saliva, the presence of anti Ro/SSA and La/SSBantibodies in serum and saliva and its implication in the noninvasivediagnosis of SS.Study Design: Cross sectional study, 73 patients divided into four experimentalgroups: Primary Sjögren's syndrome (pSS) (n = 15), secondarySS (sSS) (n = 17), dry eye and dry mouth syndrome without Sjögren's(DEMS) (n = 20) and healthy controls (C) (n = 21). We performed a determinationof basal salivary flow and saliva sampling for measurement oftotal protein, IgA, urea and antibodies. We determined anti Ro/SSA andLa/SSB in serum and saliva.Results: The salivary flow in pSS, sSS, DEMS patients was significantlylower (p <0.001) compared with C. The composition of SS salivary componentsstudied showed changes. The anti Ro/SSA and anti La/SSB occurredmore frequently in serum and saliva in SS patients comparedwith DEMS and C, the frecuency of positivity was higher in serum thanin saliva.Conclusion: The determination in saliva of antibodies Ro/SSA may helpdiagnose patients with xerostomy as Sjögren's Syndrome.

Correlación de hallazgos serológicos y compuestos orgánicos en saliva en el Síndrome de Sj§gren / Correlation of serological findings and salivaÆs organic compounds in Sj§grenÆs Syndrome

Introducción: El objetivo del presente trabajo es evaluar los cambios en flujo y composición orgánica en saliva, así como la presencia de anticuerpos anti Ro/SSA y La/SSB séricos y salivales y su implicancia en el diagnóstico no invasivo del SS. Diseño del estudio: Estudio de corte transversal, de 73 pacientes distribuidos en los siguientes grupos experimentales: Síndrome de Sj§gren primario (SSp) (n = 15), SS secundario (SSs) (n = 17), boca seca y ojo seco sin Síndrome de Sj§gren (BO) (n = 20), y controles sanos (C) (n = 21). Se realizó una determinación del flujosalivalbasal y una toma de muestras de saliva para la medición de proteínas totales, IgA, urea y anticuerpos. Se determinaron anticuerpos anti Ro/SSA y La/SSB en muestras de suero y saliva. Resultados: El flujo salival en SSp, SSs, BO fue significativamente menor (p < 0,001) comparado con C. La composición salival de SS mostró modificaciones de componentes estudiados. Los anticuerpos anti Ro/SSA y anti La/SSB aparecieron con mayor frecuencia en suero y saliva en pacientes con SS en comparación con BO y C, siendo la frecuencia de positividad superior en suero en comparación con saliva. Conclusión: La determinación de anticuerpos Ro/SSA en saliva podrían ayudar a diagnosticar a pacientes con xerostomía como el Síndrome de Sj§gren.(AU)

Introduction: The aim of this study was to evaluate changes in flow andorganic composition in saliva, the presence of anti Ro/SSA and La/SSBantibodies in serum and saliva and its implication in the noninvasivediagnosis of SS.Study Design: Cross sectional study, 73 patients divided into four experimentalgroups: Primary Sj÷grens syndrome (pSS) (n = 15), secondarySS (sSS) (n = 17), dry eye and dry mouth syndrome without Sj÷grens(DEMS) (n = 20) and healthy controls (C) (n = 21). We performed a determinationof basal salivary flow and saliva sampling for measurement oftotal protein, IgA, urea and antibodies. We determined anti Ro/SSA andLa/SSB in serum and saliva.Results: The salivary flow in pSS, sSS, DEMS patients was significantlylower (p <0.001) compared with C. The composition of SS salivary componentsstudied showed changes. The anti Ro/SSA and anti La/SSB occurredmore frequently in serum and saliva in SS patients comparedwith DEMS and C, the frecuency of positivity was higher in serum thanin saliva.Conclusion: The determination in saliva of antibodies Ro/SSA may helpdiagnose patients with xerostomy as Sj÷grens Syndrome.(AU)

Bilateral SMAS rhytidectomy in parotid recurrent pleomorphic adenoma.

A case is presented of a young female with parotid recurrent pleomorphic adenoma and skin infiltration treated with subtotal parotidectomy combined with a bilateral superficial muscular aponeurotic system rhytidectomy.

Phase II trial of paclitaxel and uracil--tegafur in metastatic breast cancer. TEGATAX trial.

UNLABELLED: This Phase II trial investigated the combination paclitaxel (P) and uracil-tegafur (UFT) in patients with metastatic breast cancer (MBC). METHODS: Main eligibility criteria included HER-2 negative MBC, ECOG performance status of 0-2, exposure to 1-2 prior chemotherapy regimen in the metastatic setting, previous exposure to an anthracycline containing regimen either at metastatic or adjuvant setting. Each 35-day cycle consisted of P at 80 mg/m(2) by intravenous infusion on days 1, 8, 15, 22 and 29 and oral UFT at 300 mg/m(2) TID (three time a day) from days 1-28 and oral folinic acid at 90 mg QD (one a day). RESULTS: Between March 2003 and December 2007, 31 patients were enrolled. Median age was 66 years (range 44-78). All tumours were HER-2 negative and 7% were triple negative (ER, PgR, HER-2). The majority of patients had visceral disease (81%). All patients had received an anthracycline containing regimen and 74% had a previous docetaxel containing treatment. Median of 4 and 3 cycles of P and UFT were administered with a relative dose intensity of 85.3% and 94.3%, respectively. Twelve (40%)(95% CI: 22.5-57.5) confirmed ORR were observed. Stable and progression disease were reported in 43% and 17% of cases. Median Response duration was 8.4 month (95% CI: 4.9-11.7), median Time to progression was 9.5 months (95% CI: 6.6-13.8) and median Overall Survival was 23.5 months (95% CI: 16.8-37.2). Thirteen pts (43%) experienced a grade 3 or 4 adverse events (AEs): One death occurred related to the study drugs (febrile neutropenia). Chemotherapy was discontinued due to toxicity in 30% of pts CONCLUSIONS: Accrual was closed in January 2008 due to concerns regarding the degree and accumulative nature of AEs. Nonetheless, the ORR is encouraging and warranted further studies with adapted doses and schedules.

Computerized physician order entry of injectable antineoplastic drugs: an epidemiologic study of prescribing medication errors.

PURPOSE: In the context of CPOE of standardized antineoplastic drugs, the objectives of the present study were to determine the incidence of prescribing medication errors (PME) and to analyse PME related to antineoplastic treatment in university teaching hospitals. METHODS: All consecutive prescribing medication orders over 1 year were analysed prospectively. Potential clinical impact was quoted according to the Hatoum scale and risk factors identified with a logistic-regression model. RESULTS: A total of 14,854 prescriptions were analysed. The PME incidence was estimated at 1.5% [1.3-1.7], i.e. 15 errors per 1000 prescribing medication orders, with a significant or very significant potential clinical impact in 62.9% of cases. Potentially death-threatening events were avoided in 3.7% of cases. Overall, PME incidence related to significant, very significant or vital potential clinical impact was estimated to be 1.0% [0.8-1.2], i.e. 10 errors per 1000 prescribing medication orders. The most common type of error was related to antineoplastic drug dosage (61.0%): inadequate adaptation (43.1%), not taking alarms into account (16.1%), incorrect weight (0.9%), incorrect unit (0.9%). More than 20% of PME are medication errors directly linked to the prescribing medication order (choice of antineoplastic treatment, double-prescribing medication order, forgotten or not validated by a resident or senior physician). Occasional users of the CPOE system and resident physicians were identified as main PME risk factors. CONCLUSION: An epidemiologic survey of PME in the context of the use of a partial CPOE has allowed to determine the incidence and epidemiology of PME as well as the potential clinical impact they represent. Two risk factors have emerged that can be considered from an organization and software points of view. Better pharmacist's analysis of prescribing medication order within the CPOE system could possibly minimize duplication of antineoplasic drugs and the vital clinical impact associated with overdosage.

Reduced in-hospital mortality for heart failure with clinical pathways: the results of a cluster randomised controlled trial.

BACKGROUND: Hospital treatment of heart failure (HF) frequently does not follow published guidelines, potentially contributing to HF high morbidity, mortality and economic cost. The Experimental Prospective Study on the Effectiveness and Efficiency of the Implementation of Clinical Pathways was undertaken to determine how clinical pathways (CP) for hospital treatment of HF affected care variability, guidelines adherence, in-hospital mortality and outcomes at discharge. Methods/ DESIGN: Two-arm, cluster-randomised trial. Fourteen community hospitals were randomised either to the experimental arm (CP: appropriate therapeutic guidelines use, new organisation and procedures, patient education) or to the control arm (usual care). The main outcome was in-hospital mortality; secondary outcomes were length and appropriateness of the stay, rate of unscheduled readmissions, customer satisfaction, usage of diagnostic and therapeutic procedures during hospital stay and quality indicators at discharge. All outcomes were measured using validated instruments available in literature. RESULTS: In-hospital mortality was 5.6% in the experimental arm (n = 12); 15.4% in controls (n = 33, p = 0.001). In CP and usual care groups, the mean rates of unscheduled readmissions were 7.9% and 13.9%, respectively. Adjusting for age, smoking, New York Heart Association score, hypertension and source of referral, patients in the CP group, as compared to controls, had a significantly lower risk of in-hospital death (OR 0.18; 95% CI 0.07 to 0.46) and unscheduled readmissions (OR 0.42; 95% CI 0.20 to 0.87). No differences were found between CP and control with respect to the appropriateness of the stay, costs and patient's satisfaction. Except for electrocardiography, all recommended diagnostic procedures were used more in the CP group. Similarly, pharmaceuticals use was significantly greater in CP, with the exception of diuretics and anti-platelets agents. DISCUSSION: The introduction of a specifically tailored CP for the hospital treatment of HF was effective in reducing in-hospital mortality and unscheduled readmissions. This study adds to previous knowledge indicating that CP should be used to improve the quality of hospital treatment of HF. TRIAL REGISTRATION NUMBER: NCT00519038.

[The results of the experimental prospective study on the effectiveness and efficiency of the implementation of clinical pathways]. / I risultati dello studio sperimentale prospettico di efficacia ed efficienza dell'implementazione dei percorsi assistenziali.

Our study was undertaken to determine how the use of care pathways in hospital affected the quality of the care of the patients. We performed a cluster-randomized trial. The use of diagnostic procedures and of medical treatments was more appropriate in the care pathways group, as well as the discharge process. As a consequence the outcomes indicators adopted in our study showed better performances in the care pathways group when compared to the usual care group. Our study added evidences on the value of clinical pathways that can be effectively used to improve the quality of hospital care. The use of CP helped to create a constant dialogue within the clinicians, ensured that important areas of treatment were not overlooked and unnecessary delays were prevented by timely interventions. We think that our results are reliable because we adopted a cluster-randomized controlled trial design that is widely accepted as the most reliable method of determining effectiveness of complex interventions in healthcare.