Clinical and immunological profile of children aged 5-9 years with persistent egg allergy before oral immunotherapy with egg. A multicenter, randomized controlled trial of the Spanish Society of Pediatric Allergy, Asthma and Clinical Immunology (SEICAP)

BACKGROUND: In children with egg protein allergy (EA), the probability of overcoming the allergy decreases with age, and the possibility of suffering severe adverse reactions as a consequence of dietetic transgressions results in worsened quality of life. One treatment option in such cases is oral immunotherapy (OIT) with foods. METHODS: We present a cohort of children with EA scheduled for OIT with pasteurized raw egg white, describing their clinical and allergic characteristics before the start of OIT. RESULTS: The median age was six years, and 93% of the patients also suffered other allergies (58% asthma and 38.6% allergy to more than two food groups). In the last year, 14.8% had suffered a severe reaction due to dietetic transgression with egg. The median IgE specific of egg white titer was 38.5 kU/l. A double-blind placebo-controlled food challenge with cooked egg white was performed, and if the test proved positive, it was repeated with pasteurized raw egg white. The mean symptoms-provoking dose was 1.26 g and 0.55 g for cooked egg white and raw egg white, respectively. An IgE specific of ovomucoid titer of <2.045 kU/l differentiated those patients that tolerated cooked egg white. CONCLUSIONS: OIT with egg is regarded as an option in patients with persistent egg allergy. In the previous challenge test, an IgE specific of ovomucoid titer of <2.045 kU/l differentiates those patients that tolerate cooked egg white

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[Pulmonary lobectomy in children: the sooner the better?] / Lobectomía pulmonar en niños: ¿cuanto antes mejor?

AIM OF THE STUDY: Recommendation of early pulmonary resection in asymptomatic congenital pulmonary airway malformations (CPAMs) is based on the presumed compensatory lung growth during the first months of life. Our aim is to analyze the long-term pulmonary function after lobectomy before and after one year of age using spirometry. METHODS: We performed a retrospective review of children who underwent pulmonary lobectomy for CPAM between 2001 and 2016. Patients who were old enough (>5 years) to carry out a spirometry were included in the study and were divided into 2 groups (surgery before or after 12 months of age). Pulmonary function testing values were considered normal if they were >80% of predicted. MAIN RESULTS: Forty-seven patients underwent pulmonary lobectomy for CPAM, 23 of them met the inclusion criteria and prospectively performed a spirometry. Among them, 7 had surgery before and 16 after one year of age (0.1 vs. 2); being both groups comparable in terms of sex, type of CPAM and surgical approach. Time from surgery until pulmonary function testing was longer in patients who had surgery before one year of age (9.1 vs. 4.6 years, p = 0.003). After correcting results by time from surgery until spirometry, a better FEV1/FVC was found in patients who had surgery after one year of age (90% vs. 77%, p = 0.043). CONCLUSION: Although spirometry may be influenced by many other variables, these preliminary results do not support the current recommendation of performing early lobectomy in CPAMs. Further studies are required in order to resolve the best age to perform pulmonary lobectomy.

INTRODUCCION/OBJETIVO: La resección temprana de las malformaciones pulmonares asintomáticas ofrece el beneficio teórico de optimizar el crecimiento pulmonar compensatorio durante la infancia. El objetivo de este estudio es determinar si la lobectomía antes del año de vida se asocia con mejor función pulmonar a largo plazo. MATERIALES Y METODOS: Revisión de pacientes en los que se realizó lobectomía pulmonar desde 2001, incluyendo los que tenían edad suficiente para realizar una espirometría (>5 años). Fueron divididos en dos grupos: lobectomía antes o después de 12 meses de vida. Los parámetros espirométricos se consideraron normales cuando eran mayores del 80% esperado. RESULTADOS: Veintitrés de los 47 pacientes intervenidos cumplieron los criterios de inclusión. Siete fueron intervenidos antes (0,1 ± 0,4 años) y 16 después del año de vida (2 ± 3,6 años), siendo ambos grupos comparables en sexo, tipo de malformación y abordaje quirúrgico. El tiempo de seguimiento desde la cirugía hasta que se realizó la espirometría fue mayor en los pacientes intervenidos antes del año de vida (9,1 vs. 4,6 años, p = 0,003). Tras corregir los resultados por el tiempo de seguimiento, se objetivó un mejor cociente FEV1/FVC en los pacientes intervenidos después del año de vida (90% vs. 77%, p = 0,043). CONCLUSION: Aunque la espirometría puede estar influenciada por otras variables, los datos de nuestro estudio no apoyan la recomendación actual de realizar resección temprana en las malformaciones pulmonares congénitas asintomáticas. Se necesitan estudios prospectivos con mayor número de pacientes para determinar la mejor edad para realizar la lobectomía.

Increased incidence of necrotizing enterocolitis associated with routine administration of Infloran™ in extremely preterm infants.

We aimed to evaluate the isolation of strains contained in the Infloran™ probiotic preparation in blood cultures and its efficacy in reducing necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in extremely preterm infants. Routine use of probiotics was implemented in 2008. Infants born at <28 weeks gestational age were prospectively followed and compared with historical controls (HC) born between 2005 and 2008. Data on sepsis due to any of the two probiotic strains contained in Infloran and rates of LOS and NEC were analysed. A total of 516 infants were included. During the probiotic period (PC), none of the strains included in the administered probiotic product were isolated from blood cultures. Probiotic administration was associated with an increase in NEC stage II or higher (HC 10/170 [5.9%]; PC 46/346 [13.3%]; P=0.010). Surgical NEC was 12.1% in PC (42/346) versus 5.9% (10/170) in HC (P=0.029). Adjusting for confounders (sex, gestational age, antenatal steroids and human milk) did not change those trends (P=0.019). Overall, clinical LOS and the incidence of staphylococcal sepsis were lower in PC (172/342, 50.3, and 37%, respectively) compared with HC (102/169, 60.3 and 50.9%, respectively) (P=0.038 and P=0.003, respectively). No episodes of sepsis attributable to the probiotic product were recorded. The period of probiotic administration was associated with an increased incidence of NEC after adjusting for neonatal factors, but also with a reduction in the LOS rate.

Clinical and immunological profile of children aged 5-9 years with persistent egg allergy before oral immunotherapy with egg. A multicenter, randomized controlled trial of the Spanish Society of Pediatric Allergy, Asthma and Clinical Immunology (SEICAP).

BACKGROUND: In children with egg protein allergy (EA), the probability of overcoming the allergy decreases with age, and the possibility of suffering severe adverse reactions as a consequence of dietetic transgressions results in worsened quality of life. One treatment option in such cases is oral immunotherapy (OIT) with foods. METHODS: We present a cohort of children with EA scheduled for OIT with pasteurized raw egg white, describing their clinical and allergic characteristics before the start of OIT. RESULTS: The median age was six years, and 93% of the patients also suffered other allergies (58% asthma and 38.6% allergy to more than two food groups). In the last year, 14.8% had suffered a severe reaction due to dietetic transgression with egg. The median IgE specific of egg white titer was 38.5kU/l. A double-blind placebo-controlled food challenge with cooked egg white was performed, and if the test proved positive, it was repeated with pasteurized raw egg white. The mean symptoms-provoking dose was 1.26g and 0.55g for cooked egg white and raw egg white, respectively. An IgE specific of ovomucoid titer of <2.045kU/l differentiated those patients that tolerated cooked egg white. CONCLUSIONS: OIT with egg is regarded as an option in patients with persistent egg allergy. In the previous challenge test, an IgE specific of ovomucoid titer of <2.045kU/l differentiates those patients that tolerate cooked egg white.

Lobectomía pulmonar en niños: ¿cuanto antes mejor? / Pulmonary lobectomy in children: the sooner the better?

Introducción/objetivo. La resección temprana de las malformaciones pulmonares asintomáticas ofrece el beneficio teórico de optimizar el crecimiento pulmonar compensatorio durante la infancia. El objetivo de este estudio es determinar si la lobectomía antes del año de vida se asocia con mejor función pulmonar a largo plazo. Materiales y métodos. Revisión de pacientes en los que se realizó lobectomía pulmonar desde 2001, incluyendo los que tenían edad suficiente para realizar una espirometría (>5 años). Fueron divididos en dos grupos: lobectomía antes o después de 12 meses de vida. Los parámetros espirométricos se consideraron normales cuando eran mayores del 80% esperado. Resultados. Veintitrés de los 47 pacientes intervenidos cumplieron los criterios de inclusión. Siete fueron intervenidos antes (0,1 ± 0,4 años) y 16 después del año de vida (2 ± 3,6 años), siendo ambos grupos comparables en sexo, tipo de malformación y abordaje quirúrgico. El tiempo de seguimiento desde la cirugía hasta que se realizó la espirometría fue mayor en los pacientes intervenidos antes del año de vida (9,1 vs. 4,6 años, p = 0,003). Tras corregir los resultados por el tiempo de seguimiento, se objetivó un mejor cociente FEV1/FVC en los pacientes intervenidos después del año de vida (90% vs. 77%, p = 0,043). Conclusión. Aunque la espirometría puede estar influenciada por otras variables, los datos de nuestro estudio no apoyan la recomendación actual de realizar resección temprana en las malformaciones pulmonares congénitas asintomáticas. Se necesitan estudios prospectivos con mayor número de pacientes para determinar la mejor edad para realizar la lobectomía

Aim of the study. Recommendation of early pulmonary resection in asymptomatic congenital pulmonary airway malformations (CPAMs) is based on the presumed compensatory lung growth during the first months of life. Our aim is to analyze the long-term pulmonary function after lobectomy before and after one year of age using spirometry. Methods. We performed a retrospective review of children who underwent pulmonary lobectomy for CPAM between 2001 and 2016. Patients who were old enough (>5 years) to carry out a spirometry were included in the study and were divided into 2 groups (surgery before or after 12 months of age). Pulmonary function testing values were considered normal if they were >80% of predicted. Main results. Forty-seven patients underwent pulmonary lobectomy for CPAM, 23 of them met the inclusion criteria and prospectively performed a spirometry. Among them, 7 had surgery before and 16 after one year of age (0.1 vs. 2); being both groups comparable in terms of sex, type of CPAM and surgical approach. Time from surgery until pulmonary function testing was longer in patients who had surgery before one year of age (9.1 vs. 4.6 years, p = 0.003). After correcting results by time from surgery until spirometry, a better FEV1/FVC was found in patients who had surgery after one year of age (90% vs. 77%, p = 0.043). Conclusion. Although spirometry may be influenced by many other variables, these preliminary results do not support the current recommendation of performing early lobectomy in CPAMs. Further studies are required in order to resolve the best age to perform pulmonary lobectomy

Radiation dose optimisation for conventional imaging in infants and newborns using automatic dose management software: an application of the new 2013/59 EURATOM directive.

Objective: The new 2013/59 EURATOM Directive (ED) demands dosimetric optimisation procedures without undue delay. The aim of this study was to optimise paediatric conventional radiology examinations applying the ED without compromising the clinical diagnosis. METHODS: Automatic dose management software (ADMS) was used to analyse 2678 studies of children from birth to 5 years of age, obtaining local diagnostic reference levels (DRLs) in terms of entrance surface air kerma. Given local DRL for infants and chest examinations exceeded the European Commission (EC) DRL, an optimisation was performed decreasing the kVp and applying the automatic control exposure. To assess the image quality, an analysis of high-contrast resolution (HCSR), signal-to-noise ratio (SNR) and figure of merit (FOM) was performed, as well as a blind test based on the generalised estimating equations method. RESULTS: For newborns and chest examinations, the local DRL exceeded the EC DRL by 113%. After the optimisation, a reduction of 54% was obtained. No significant differences were found in the image quality blind test. A decrease in SNR (-37%) and HCSR (-68%), and an increase in FOM (42%), was observed. CONCLUSION: ADMS allows the fast calculation of local DRLs and the performance of optimisation procedures in babies without delay. However, physical and clinical analyses of image quality remain to be needed to ensure the diagnostic integrity after the optimisation process. Advances in knowledge: ADMS are useful to detect radiation protection problems and to perform optimisation procedures in paediatric conventional imaging without undue delay, as ED requires.

Sensitivity and specificity of the lymphocyte transformation test in drug reaction with eosinophilia and systemic symptoms causality assessment.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe delayed hypersensitivity reaction. The determination of drug causality is complex. The lymphocyte transformation test (LTT) has been reported positive in more than 50% of DRESS cases. Nevertheless, the sensitivity and specificity of LTT specifically in DRESS have not yet been established. Rechallenge with the culprit drug is contraindicated and cannot be used as gold standard for sensitivity and specificity determination. OBJECTIVE: To estimate the sensitivity and specificity of LTT in a clinically defined series of patients with DRESS. METHODS: Some 41 patients diagnosed with DRESS were included in the study. The results of the algorithm of the Spanish Pharmacovigilance System were used as the standard for a correct diagnosis of drug causality. A standard LTT was performed with involved drugs in acute or recovery samples. A stimulation index (SI) ≥2 in at least one concentration except for beta-lactams (SI ≥3) and contrast media (SI ≥4) was considered positive. Contingency tables and ROC curves were used for analysis. RESULTS: Sensitivity and specificity of LTT in the recovery phase of DRESS were 73% and 82%, respectively, whereas in the acute phase, they were only 40% and 30%, respectively. Comparison of skin tests and LTT confirmed a higher sensitivity and specificity of LTT in DRESS. LTT showed high sensitivity (S) and specificity (Sp) for anticonvulsants (S 100%, Sp 100%; P = .008), anti-TB drugs (S 87.5%, Sp 100%; P = .004), and beta-lactams (S 73%, Sp 100%; P = .001). ROC curves revealed that the best criteria for LTT positivity for all drugs are SI ≥2 in at least one concentration, increasing overall sensitivity to 80%, and for beta-lactams from 73% to 92%. CONCLUSIONS AND CLINICAL RELEVANCE: LTT is a good diagnostic tool for drug causality in DRESS, mainly when performed in the recovery phase.

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab.

BACKGROUND: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. METHODS: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. RESULTS: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). CONCLUSIONS: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.

Estudio retrospectivo de diferentes opciones de tratamiento conservador con Bacilo de Calmette-Guèrin en el carcinoma urotelial vesical T1G3: terapia de mantenimiento / Retrospective study of various conservative treatment options with bacille Calmette-Guérin in bladder urothelial carcinoma T1G3: Maintenance therapy

Objetivo: Comparar diferentes opciones de tratamiento conservador del tumor vesical no músculo-invasivo (TVNMI) T1 de grado alto. El bacilo de Calmette-Guérin (BCG) es el tratamiento intravesical preferido para los tumores T1 de grado alto; sin embargo, algunos expertos aún cuestionan la necesidad de la BCG de mantenimiento. Materiales y métodos: Se analizaron retrospectivamente los datos de 1.039 pacientes con TVNMI T1G3 primario y recurrente. Todos los pacientes fueron tratados mediante una resección transuretral del tumor vesical (RTUTV) completa, con músculo en la muestra y múltiples biopsias de la vejiga. Los pacientes fueron tratados con solo una RTUTV inicial (n = 108), re-RTUTV (n = 153), inducción con 27 mg de BCG (cepa Connaught) (n = 87), inducción con 81 mg de BCG (n = 489) o inducción con 81 mg de BCG + mantenimiento (n = 202). El tiempo hasta la primera recidiva, progresión (a T2 o mayor, o a enfermedad metastásica) y mortalidad específica de la enfermedad se evaluaron mediante la función de supervivencia de Kaplan-Meier y se compararon utilizando la prueba de logaritmo del rango (log-rank) y el modelo multivariado de regresión de Cox de riesgos proporcionales. Resultados: El seguimiento medio fue de 62 ± 39 meses. El riesgo de recurrencia fue significativamente menor en los pacientes tratados con terapia de mantenimiento con 81 mg de BCG que en los otros grupos de tratamiento (p < 0,001). El riesgo de progresión del tumor también fue significativamente más bajo en los pacientes tratados con mantenimiento con BCG que en los pacientes tratados solo con una RTUTV, re-RTUTV y con terapia de inducción con 27 mg de BCG (p = 0,0003). La mortalidad específica de la enfermedad fue significativamente más baja con el mantenimiento con BCG (9,4%) que con solo una RTUTV (27,8%; p = 0,003). Conclusiones: En el caso del TVNMI T1G3, la dosis completa de BCG con mantenimiento va asociada a mejores resultados de recurrencia que otras modalidades de tratamiento conservador. Los resultados de progresión y de supervivencia específica de la enfermedad también fueron mejores con la BCG de inducción, con o sin mantenimiento

Objective: To compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guérin (BCG) is the preferred intravesical treatment for high-grade T1 tumours; however, a number of experts still question the need for maintenance BCG. Material and methods: We retrospectively analysed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumour (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n = 108), re-TURBT (n = 153), induction with 27 mg of BCG (Connaught strain) (n = 87), induction with 81 mg of BCG (n = 489) or induction with 81 mg of BCG + maintenance (n = 202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan-Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. Results: The mean follow-up was 62 ± 39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81 mg of BCG than in the other treatment groups (P<.001). The risk of tumour progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27 mg of BCG (P=.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; P=.003). Conclusions: In the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance

Retrospective study of various conservative treatment options with bacille Calmette-Guérin in bladder urothelial carcinoma T1G3: Maintenance therapy. / Estudio retrospectivo de diferentes opciones de tratamiento conservador con Bacilo de Calmette-Guèrin en el carcinoma urotelial vesical T1G3: terapia de mantenimiento.

OBJECTIVE: To compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guérin (BCG) is the preferred intravesical treatment for high-grade T1 tumours; however, a number of experts still question the need for maintenance BCG. MATERIAL AND METHODS: We retrospectively analysed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumour (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n=108), re-TURBT (n=153), induction with 27mg of BCG (Connaught strain) (n=87), induction with 81mg of BCG (n=489) or induction with 81mg of BCG+maintenance (n=202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan-Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. RESULTS: The mean follow-up was 62±39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81mg of BCG than in the other treatment groups (P<.001). The risk of tumour progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27mg of BCG (P=.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; P=.003). CONCLUSIONS: In the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance.

Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

Background: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. Patients and methods: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student’s t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson’s correlation coefficient. Results: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP(p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. Conclusions: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy (AU)

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SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases

Purpose. Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. Patients and methods. A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient’s outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. Results. Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422–0.944) and SMAD4 (HR 1.680, 95 % CI 1.047–2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. Conclusions. The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence (AU)

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SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases.

PURPOSE: Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. PATIENTS AND METHODS: A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient's outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. RESULTS: Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422-0.944) and SMAD4 (HR 1.680, 95 % CI 1.047-2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. CONCLUSIONS: The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence.

Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

BACKGROUND: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. PATIENTS AND METHODS: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student's t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson's correlation coefficient. RESULTS: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP (p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. CONCLUSIONS: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy.

Clinical outcome following conversion of Girdlestone's resection arthroplasty to total hip replacement: a retrospective matched case-control study.

A total of 31 patients, (20 women, 11 men; mean age 62.5 years old; 23 to 81), who underwent conversion of a Girdlestone resection-arthroplasty (RA) to a total hip replacement (THR) were compared with 93 patients, (60 women, 33 men; mean age 63.4 years old; 20 to 89), who had revision THR surgery for aseptic loosening in a retrospective matched case-control study. Age, gender and the extent of the pre-operative bone defect were similar in all patients. Mean follow-up was 9.3 years (5 to 18). Pre-operative function and range of movement were better in the control group (p = 0.01 and 0.003, respectively) and pre-operative leg length discrepancy (LLD) was greater in the RA group (p < 0.001). The post-operative clinical outcome was similar in both groups except for mean post-operative LLD, which was greater in the study group (p = 0.003). There was a significant interaction effect for LLD in the study group (p < 0.001). A two-way analysis of variance showed that clinical outcome depended on patient age (patients older than 70 years old had worse pre-operative pain, p = 0.017) or bone defect (patients with a large acetabular bone defect had higher LLD, p = 0.006, worse post-operative function p = 0.009 and range of movement, p = 0.005), irrespective of the group. Despite major acetabular and femoral bone defects requiring complex surgical reconstruction techniques, THR after RA shows a clinical outcome similar to those obtained in aseptic revision surgery for hips with similar sized bone defects.

Influencia del número real de instilaciones de Bacilo de Calmette-Guérin aplicadas en el pronóstico de los tumores vesicales no músculo-infiltrantes / Influence of the true number of Bacillus Calmette-Guérin instillations on the prognosis of non-muscle invasive bladder tumors

Objetivos: Analizar si el número real de instilaciones de BCG aplicadas en los tumores vesicales no músculo-infiltrantes tiene alguna influencia en su pronóstico, así como otras variables clínicas y del tumor: edad, sexo, diferentes protocolos, dosis de BCG, primario o recurrente, G3 o Cis. Pacientes y métodos: De 1.491 pacientes incluidos en la base de datos del grupo CUETO se analizaron 324 tumores de alto grado (15 TaG3, 184 T1G3, 125 Cis). Tras la inducción de 6 instilaciones de BCG post-RTU fueron programados para recibir una instilación cada 2 semanas (3-6 veces), total 9-12 instilaciones. Un tercio de dosis (27 mg) en 112 casos y dosis total (81 mg) en 212 casos. Seguimiento medio: 59,6 meses. Análisis estadístico: Kaplan-Meier, regresión de Cox uni y multivariado. Resultados: Con el análisis de Kaplan-Meier y regresión de Cox multivariado se obtuvo mayor riesgo de recidiva (p = 0,032) y progresión (p = 0,013), y peor supervivencia cáncer-específica (p = 0,005) si < de 12 instilaciones. Dosis de 27 mg (p = 0,008) y el ser mujer (p < 0,001) fueron factores independientes predictivos de mayor recidiva, pero no de mayor progresión ni de peor supervivencia cáncer-específica. El resto de las características estudiadas no fueron estadísticamente significativas. Conclusiones: Con los resultados obtenidos parece que el número de instilaciones aplicadas tiene alguna influencia sobre el pronóstico, quedando por determinar cuál es el mínimo de instilaciones a partir del cual el paciente se puede beneficiar y su tiempo de aplicación. Dosis de 27 mg y el ser mujer son factores predictivos para mayor recidiva

Objectives: To analyze if the true number of BCG instillations applied in non-muscle invasive bladder tumors has any influence on their prognosis as well as other tumor and clinical characteristics: age, sex, different protocols, BCG dose, whether primary or recurrent, solitary or multiple, tumor size G3 or Cis. Patients and methods: A total of 324 high grade NMIBC (15 TaG3, 184 T1G3, 125 Cis) out of 1491 cases included in the CUETO database were analyzed. Following 6 post transurethral resection (RTU) BCG instillations, the patients were scheduled to receive one instillation every two weeks (3-6 times), for a total of 9-12 instillations. One third of the dose (27 mg) (112 cases) or total dose of 81 mg (212 cases). Mean follow-up was 59.6 months. Statistical Analysis: Kaplan-Meier, Cox-regression (uni-multivariate). Results: A higher level of recurrence (p = 0.032) and progression (p = 0.013) risk as well as worse Ca-specific survival (p = 0.005) were obtained if there were fewer than 12 instillations with the Kaplan-Meier and Cox-regression multivariate analysis. A 27 mg (p = 0.008) dosage and being a female (p < 0.001) were independent factors for a higher recurrence risk, but not for progression or Ca-specific survival. The remaining characteristics studied were not statistically significant. Conclusions: In accordance with the results obtained, we can conclude that the number of BCG instillations applied has some influence on the outcome of high grade NMIBC. The optimum number of instillations as well as their time of application must still be determined. A dose of 27 mg and being a female are predictive factors of recurrence

Influence of the true number of Bacillus Calmette-Guérin instillations on the prognosis of non-muscle invasive bladder tumors.

OBJECTIVES: To analyze if the true number of BCG instillations applied in non-muscle invasive bladder tumors has any influence on their prognosis as well as other tumor and clinical characteristics: age, sex, different protocols, BCG dose, whether primary or recurrent, solitary or multiple, tumor size G3 or Cis. PATIENTS AND METHODS: A total of 324 high grade NMIBC (15 TaG3, 184 T1G3, 125 Cis) out of 1491 cases included in the CUETO database were analyzed. Following 6 post transurethral resection (RTU) BCG instillations, the patients were scheduled to receive one instillation every two weeks (3-6 times), for a total of 9-12 instillations. One third of the dose (27 mg) (112 cases) or total dose of 81 mg (212 cases). Mean follow-up was 59.6 months. Statistical Analysis: Kaplan-Meier, Cox-regression (uni-multivariate). RESULTS: A higher level of recurrence (p = 0.032) and progression (P = .013) risk as well as worse Ca-specific survival (P = .005) were obtained if there were fewer than 12 instillations with the Kaplan-Meier and Cox-regression multivariate analysis. A 27 mg (P = .008) dosage and being a female (P < .001) were independent factors for a higher recurrence risk, but not for progression or Ca-specific survival. The remaining characteristics studied were not statistically significant. CONCLUSIONS: In accordance with the results obtained, we can conclude that the number of BCG instillations applied has some influence on the outcome of high grade NMIBC. The optimum number of instillations as well as their time of application must still be determined. A dose of 27 mg and being a female are predictive factors of recurrence.

Pharmacogenetic predictors of severe peripheral neuropathy in colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy: a GEMCAD group study.

BACKGROUND: Oxaliplatin-based chemotherapy (CT), widely used as adjuvant therapy for stage III and selected high-risk stage II colon cancer (CC) patients, is often associated with cumulative peripheral neuropathy. Our aim is to identify single-nucleotide polymorphisms (SNPs) in genes involved in oxaliplatin metabolism, DNA repair mechanisms, cell cycle control, detoxification or excretion pathways to predict severe (grade 2-3) oxaliplatin-induced peripheral neuropathy (OXPN) among CC patients treated with oxaliplatin and fluoropyrimidine-based adjuvant CT. PATIENTS AND METHODS: Genomic DNA was extracted from formalin-fixed-paraffin-embedded peritumoral samples from 206 high-risk stage II and stage III CC patients receiving oxaliplatin-based adjuvant CT from January 2004 to December 2009. Genotyping was carried out for 34 SNPs in 15 genes using MassARRAY (SEQUENOM) technology. A total of 181 stage II-III CC patients treated with the same CT regimens were enrolled as a validation set. RESULTS: The rs2230641 cyclin H (CCNH) rs2230641 C/C [odd ratio (OR)=5.03, 95% confidence interval (CI) 1.061-2.41, P=0.042] and the ATP-binding cassette subfamily G, member 2 (ABCG2) rs3114018 A/A genotypes (OR=2.67; 95% CI 0.95-4.41; P=0.059) were associated with a higher risk of severe OXPN. In addition, patients harboring the combination of CCNH C/C and/or the ABCG2 rs3114018 A/A genotypes had a higher risk of grade 2-3 OXPN than those with the CCNH any T and ABCG2 any C genotypes (37.73% versus 19.42%; OR=2.46; 95% CI 1.19-5.07; P=0.014) in the logistic regression analysis using age, gender, adjuvant CT regimen and cumulative dose of oxaliplatin as covariates. The ability to predict severe OXPN of this combined analysis was independently validated in the second cohort (58% versus 33.33%; OR=2.99; 95% CI 1.45-6.13; P=0.002). CONCLUSIONS: Our results suggest that SNPs in CCNH and ABCG2 can modulate the development of severe OXPN among stage II-III CC patients who received oxaliplatin-based CT, thus enabling the individualization of adjuvant treatment.

Tamizaje para sífilis en donantes de sangre y reactividad simultánea con otros marcadores en la Fundación Hematológica Colombia / Screening for syphilis in blood donors and simultaneous reactivity with other markers in the Fundación Hematológica Colombia / O rastreamento da sífilis em doadores de sangue e reativida- de simultânea com outros marcadores na Fundação Hemato - logia da Colombia

El presente artículo se propone caracterizar los donantes voluntarios de sangre que presentaron reactividad contra \r\nTreponema pallidum\r\n durante el periodo 2006-2011 y conocer la reactividad simultánea con otros marcadores en un \r\nbanco de sangre colombiano. Para ello, se realizó un estudio retrospectivo de corte transversal en el banco de sangre \r\nFundación Hematológica Colombia, Bogotá (Colombia). La población de estudio estuvo conformada por registros de \r\ndonantes voluntarios de sangre que presentaron reactividad en el tamizaje para \r\nTreponema pallidum\r\n y otros marca\r\n-\r\ndores entre 2006 y 2011.\r\nLa población de estudio estuvo conformada por 11.203 registros de donantes voluntarios de sangre, el promedio de \r\nedad fue de 43,27 ± 12,04 años, de los cuales el 56,2% (n=6.296) pertenecía al género masculino, el 11,1% (n=1.246) \r\nde los sujetos con tamizaje para sífilis presentaron coinfección para los marcadores de reactividad simultánea con \r\nsífilis; el de mayor presentación fue Anti-Core con un 67,7% (n=900), seguido de VIH con 10,3%. La prevalencia de \r\nsífilis del periodo de estudio fue de 1,9%.\r\nEn conclusión, se logró describir claramente las características generales de la población con tamizaje para sífilis, \r\nademás se encontraron datos estadísticamente significativos por género. Es importante conocer este tipo de compor\r\n-\r\ntamiento con el fin de fortalecer los procesos de selección de donantes de sangre y demostrar que la reactividad \r\nsimultánea no es un proceso aislado en un banco de sangre.

Objective: describe voluntary blood donors who showed \r\nreactivity to Treponema pallidum during 2006-2011 and \r\nto identify simultaneous reactivity with other markers \r\nin a Colombian blood bank. Materials and methods: a \r\nretrospective cross-sectional study was performed at the \r\nFundación Hematológica Colombia, Bogotá-Colombia. \r\nThe records of volunteer blood donors that showed reac\r\n-\r\ntivity for screening for Treponema pallidum and other \r\nmarkers of simultaneous screening during 2006-2011 \r\nwere included. Results: A total of 11.203 records of \r\nvoluntary blood donors were included; the mean age was \r\n43.27 ± 12.04 years, 56.2% males (n = 6.296), 11.1% \r\n(n = 1.246) of subjects with syphilis had co-infection \r\nand syphilis screening for markers simultaneous reacti\r\n-\r\nvity with syphilis. The greatest incidence was Anti Core \r\nwith 67.7% (n = 900), followed by HIV with 10.3%, \r\nthe prevalence of syphilis of the study period was 1.9%. \r\nConclusions: the general characteristics of the popula\r\n-\r\ntion with syphilis screening were clearly determined. \r\nThere is a statistically significant difference among the \r\ngenders. It is important to note this kind of behavior in \r\norder to reinforce the processes of blood donor selection, \r\nand to demonstrate that simultaneous reactivity is not an \r\nisolated process in the blood bank.

Objetivo: caracterizar os doadores voluntários de sangue \r\nque apresentaram reatividade contra \r\nTreponema pallidum\r\ndurante 2006-2011 e para conhecer a reatividade simul\r\n-\r\ntânea com outros marcadores em um banco de sangue \r\nna Colombia. Materiais e métodos: foi realizado um \r\nestudo transversal retrospectivo no banco de sangue da \r\nFundação de Hematologia Colombia, Bogotá, Colombia. \r\nA população do estudo consistiu de registros de doadores \r\nde sangue voluntários que apresentaram reatividade para \r\na triagem de Treponema pallidum e outros marcadores \r\ndurante 2006-2011. Resultados: a população do estudo \r\nconsistiu de 11.203 registros de doadores voluntários de \r\nsangue, a idade média foi de 43,27 ± 12,04 anos, sendo \r\nque 56,2% (n = 6.296) pertenciam ao sexo masculino, \r\n11,1% (n = 1.246) dos indivíduos tiveram co-infecção \r\npara os marcadores reatividade simultânea com a sífilis, \r\na maior incidência foi de Anti-Core com 67,7% (n = \r\n900), seguido por HIV com 10,3%, a prevalência de \r\nsífilis do período de estudo foi de 1,9%. Conclusão: foi \r\npossível descrever claramente as características gerais \r\nda população com sífilis também encontramos dados \r\nestatisticamente significativas por sexo. É importante \r\nconhecer esse tipo de comportamento, a fim de fortalecer \r\nos processos de seleção de doadores de sangue e também \r\nmostrar que a reatividade simultânea não é um processo \r\nisolado no banco de sangue.

Prevalence of and risk factors for biliary carriage of bacteria showing worrisome and unexpected resistance traits.

Data on biliary carriage of bacteria and, specifically, of bacteria with worrisome and unexpected resistance traits (URB) are lacking. A prospective study (April 2010 to December 2011) was performed that included all patients admitted for <48 h for elective laparoscopic cholecystectomy in a Spanish hospital. Bile samples were cultured and epidemiological/clinical data recorded. Logistic regression models (stepwise) were performed using bactobilia or bactobilia by URB as dependent variables. Models (P < 0.001) showing the highest R(2) values were considered. A total of 198 patients (40.4% males; age, 55.3 ± 17.3 years) were included. Bactobilia was found in 44 of them (22.2%). The presence of bactobilia was associated (R(2) Cox, 0.30) with previous biliary endoscopic retrograde cholangiopancreatography (ERCP) (odds ratio [OR], 8.95; 95% confidence interval [CI], 2.96 to 27.06; P < 0.001), previous admission (OR, 2.82; 95% CI, 1.10 to 7.24; P = 0.031), and age (OR, 1.09 per year; 95% CI, 1.05 to 1.12; P < 0.001). Ten out of the 44 (22.7%) patients with bactobilia carried URB: 1 Escherichia coli isolate (CTX-M), 1 Klebsiella pneumoniae isolate (OXA-48), 3 high-level gentamicin-resistant enterococci, 1 vancomycin-resistant Enterococcus isolate, 3 Enterobacter cloacae strains, and 1 imipenem-resistant Pseudomonas aeruginosa strain. Bactobilia by URB (versus those by non-URB) was only associated (R(2) Cox, 0.19) with previous ERCP (OR, 11.11; 95% CI, 1.98 to 62.47; P = 0.006). For analyses of patients with bactobilia by URB versus the remaining patients, previous ERCP (OR, 35.284; 95% CI, 5.320 to 234.016; P < 0.001), previous intake of antibiotics (OR, 7.200; 95% CI, 0.962 to 53.906; P = 0.050), and age (OR, 1.113 per year of age; 95% CI, 1.028 to 1.206; P = 0.009) were associated with bactobilia by URB (R(2) Cox, 0.19; P < 0.001). Previous antibiotic exposure (in addition to age and previous ERCP) was a risk driver for bactobilia by URB. This may have implications in prophylactic/therapeutic measures.