Study of paediatric patients with the clinical and biochemical phenotype of glucose transporter type 1 deficiency syndrome.

INTRODUCTION: Glucose transporter type 1 (GLUT1) deficiency syndrome may present a range of phenotypes, including epilepsy, intellectual disability, and movement disorders. The majority of patients present low CSF glucose levels and/or defects in the SLC2A1 gene; however, some patients do not present low CSF glucose or SLC2A1 mutations, and may have other mutations in other genes with compatible phenotypes. AIMS: We describe the clinical, biochemical, and genetic characteristics of the disease and perform a univariate analysis of a group of patients with clinical and biochemical phenotype of GLUT1 deficiency syndrome, with or without SLC2A1 mutations. MATERIAL AND METHODS: The study included 13 patients meeting clinical and biochemical criteria for GLUT1 deficiency syndrome. SLC2A1 sequencing and multiplex ligation-dependent probe amplification were performed; exome sequencing was performed for patients with negative results. RESULTS: Six patients presented the classic phenotype; 2 paroxysmal dyskinesia, 2 complex movement disorders, 2 early-onset absence seizures, and one presented drug-resistant childhood absence epilepsy. Six patients were positive for SLC2A1 mutations; in the other 5, another genetic defect was identified. No significant differences were observed between the 2 groups for age of onset, clinical presentation, microcephaly, intellectual disability, or response to ketogenic diet. Patients with SLC2A1 mutations presented more clinical changes in relation to diet (66.7%, vs 28.6% in the SLC2A1-negative group) and greater persistence of motor symptoms (66% vs 28.6%); these differences were not statistically significant. Significant differences were observed for CSF glucose level (34.5 vs 46mg/dL, P=.04) and CSF/serum glucose ratio (0.4 vs 0.48, P<.05). CONCLUSIONS: GLUT1 deficiency syndrome may be caused by mutations to genes other than SLC2A1 in patients with compatible phenotype, low CSF glucose level, and good response to the ketogenic diet.

Estudio de pacientes pediátricos con fenotipo clínico y bioquímico de síndrome de déficit de transportador de glucosa cerebral (GLUT-1) / Study of paediatric patients with the clinical and biochemical phenotype of glucose transporter type 1 deficiency syndrome

Introducción: El síndrome de déficit del transportador de glucosa cerebral (GLUT1DS) puede presentar fenotipos variados, incluyendo epilepsia, déficit intelectual y trastorno del movimiento. La mayoría presenta hipoglucorraquia y/o defectos en el gen SLC2A1, aunque existen pacientes sin hipoglucorraquia y otros con genética de SLC2A1-negativa, o con defectos en otros genes y fenotipo compatible. Objetivos: Describir las características clínicas, bioquímicas y genéticas y realizar un análisis univariante de un grupo de pacientes con fenotipo clínico y bioquímico de GLUT1DS, con o sin genética SLC2A1-positiva. Material y métodos: Se incluyeron 13 pacientes con criterios clínico-bioquímicos de GLUT1DS. Se realizó secuenciación de SLC2A1 y MLPA. En los casos negativos se realizó exoma clínico. Resultados: Seis presentaron fenotipo clásico, 2 discinesia paroxística, 2 trastornos del movimiento complejo, 2 ausencias precoces y otro presentó epilepsia con ausencias infantiles refractaria a farmacoterapia. Seis fueron SLC2A1-positivos. Y en 5 de los SLC2A1-negativos se identificó otro defecto genético. No hubo diferencias significativas entre los dos grupos en edad de inicio, presentación clínica, microcefalia, discapacidad intelectual ni respuesta a dieta cetogénica. De forma no significativa, los pacientes SCL2A1-positivos presentaron más cambios clínicos en relación con la ingesta (66,7% vs. 28,6%) y mayor persistencia de síntomas motores (66% vs. 28,6%). De forma significativa, presentaron menor glucorraquia (34,5 mg/dl vs. 46 mg/dl, p = 0,04) e índice glucorraquia/glucemia más bajo (0,4 vs. 0,48, p = 0,05) que los SLC2A1-negativos. Conclusiones: GLUT1DS puede ser causado por defectos genéticos en otros genes diferentes de SLC2A1 en pacientes con fenotipo compatible, hipoglucorraquia y buena respuesta a dieta cetogénica. (AU)

Introduction: Glucose transporter type 1 (GLUT1) deficiency syndrome may present a range of phenotypes, including epilepsy, intellectual disability, and movement disorders. The majority of patients present low CSF glucose levels and/or defects in the SLC2A1 gene; however, some patients do not present low CSF glucose or SLC2A1 mutations, and may have other mutations in other genes with compatible phenotypes. Aims: We describe the clinical, biochemical, and genetic characteristics of the disease and perform a univariate analysis of a group of patients with clinical and biochemical phenotype of GLUT1 deficiency syndrome, with or without SLC2A1 mutations. Material and methods: The study included 13 patients meeting clinical and biochemical criteria for GLUT1 deficiency syndrome. SLC2A1 sequencing and multiplex ligation-dependent probe amplification were performed; exome sequencing was performed for patients with negative results. Results: Six patients presented the classic phenotype; 2 paroxysmal dyskinesia, 2 complex movement disorders, 2 early-onset absence seizures, and one presented drug-resistant childhood absence epilepsy. Six patients were positive for SLC2A1mutations; in the other 5, another genetic defect was identified. No significant differences were observed between the 2 groups for age of onset, clinical presentation, microcephaly, intellectual disability, or response to ketogenic diet. Patients ith SLC2A1 mutations presented more clinical changes in relation to diet (66.7% vs. 28.6% in the SLC2A1-negative group) and greater persistence of motor symptoms (66% vs. 28.6%); these differences were not statistically significant. Significant differences were observed for CSF glucose level (34.5 vs. 46 mg/dL, P = .04) and CSF/serum glucose ratio (0.4 vs. 0.48, P < .05). [...] (AU)

Pediatric septic thrombosis of intracranial venous sinuses: from diagnosis to discharge. Twenty years of experience. / Trombosis séptica pediátrica de senos venosos intracraneales: del diagnóstico al alta. Veinte años de experiencia.

INTRODUCTION: Septic thrombosis of intracranial venous sinuses (STSV) is a rare and severe complication of cranial infections. MATERIALS AND METHODS: The main objective of this paper is to describe the clinical data, diagnostic procedures, treatment and evolution of a series of cases of STSV. In addition, the current literature is reviewed. Observational retrospective study by review of medical histories (January 1995-December 2016). The data collected were: clinical, analytical, epidemiological, microbiological, radiological, management and follow-up. A descriptive and statistical analysis of the data was done. RESULTS: Twelve children were included (86,832 admissions studied). They have a median age of 4.5 years (range 1-13) with a median time of symptoms of 6 days (range 1-25). At admission, the clinical data were: fever (11/12), vomiting (9/12) and headache (8/12). They also showed bad general status 12/12, 7/12 acute otitis media and 5/12 VI cranial nerve paresis. The lumbar puncture was pathological in 4/12. The most frequently microorganism isolated was Streptococcus sp. Prothrombotic mutations were confirmed on 2/12. Cranial computed tomography allowed diagnosis in 9/12; the magnetic resonance imaging achieves that in 12/12. Previous neurological signs or time to diagnosis did not influence the appearance of other image complications. All received antibiotic treatment, heparin 10/12 and 11/12 surgery. There were no sequels. CONCLUSION: In our series otitis, headache, vomiting and fever were prevalent. Complementary tests allowed the suspect but the definitive diagnosis was obtained by neuroimaging. There were no sequels and the therapies were mainly wide broad-spectrum antibiotics, heparin, and surgical.

TITLE: Trombosis séptica pediátrica de senos venosos intracraneales: del diagnóstico al alta. Veinte años de experiencia.Introducción. La trombosis séptica de los senos venosos intracraneales (TSSV) es una complicación rara y grave de las infecciones craneales. Materiales y métodos. El objetivo principal de este trabajo es describir los datos clínicos, procedimientos diagnósticos, tratamiento y evolución de una serie de casos de TSSV. Además, se revisa la bibliografía actual. Es un estudio retrospectivo observacional mediante revisión de historias médicas (enero de 1995-diciembre de 2016). Los datos recogidos fueron: clínicos, analíticos, epidemiológicos, microbiológicos, radiológicos, de manejo y de seguimiento. Se realizó un análisis descriptivo y estadístico de los datos. Resultados. Se incluyó a 12 niños (86.832 ingresos estudiados). La mediana de edad fue de 4,5 años (rango: 1-13), con un tiempo medio de síntomas de 6 días (rango: 1-25). En el momento de la admisión, los datos clínicos fueron: fiebre (11/12), vómitos (9/12) y dolor de cabeza (8/12). También mostraron mal estado general, 12/12; otitis media aguda, 7/12; y paresia del VI par craneal, 5/12. La punción lumbar fue patológica en 4/12. El microorganismo más frecuentemente aislado fue Streptococcus spp. Se confirmaron mutaciones protrombóticas en 2/12. La tomografía computarizada craneal permitió el diagnóstico en 9/12; la resonancia magnética lo logró en 12/12. Los signos neurológicos anteriores o el tiempo de diagnóstico no influyeron en la aparición de otras complicaciones de la imagen. Recibieron tratamiento antibiótico 12/12; heparina, 10/12; y cirugía, 11/12. No hubo secuelas. Conclusión. En nuestra serie, la otitis, el dolor de cabeza, los vómitos y la fiebre fueron frecuentes. Las pruebas complementarias permitieron el diagnóstico de sospecha, pero el diagnóstico definitivo se obtuvo por neuroimagen. No hubo secuelas y las terapias fueron principalmente antibióticos de amplio espectro, heparina y cirugía.

Trombosis séptica pediátrica de senos venosos intracraneales: del diagnóstico al alta. Veinte años de experiencia / Pediatric septic thrombosis of intracranial venous sinuses: from diagnosis to discharge. Twenty years of experience

Introducción: La trombosis séptica de los senos venosos intracraneales (TSSV) es una complicación rara y grave de las infecciones craneales. Materiales y métodos: El objetivo principal de este trabajo es describir los datos clínicos, procedimientos diagnósticos, tratamiento y evolución de una serie de casos de TSSV. Además, se revisa la bibliografía actual. Es un estudio retrospectivo observacional mediante revisión de historias médicas (enero de 1995-diciembre de 2016). Los datos recogidos fueron: clínicos, analíticos, epidemiológicos, microbiológicos, radiológicos, de manejo y de seguimiento. Se realizó un análisis descriptivo y estadístico de los datos. Resultados: Se incluyó a 12 niños (86.832 ingresos estudiados). La mediana de edad fue de 4,5 años (rango: 1-13), con un tiempo medio de síntomas de 6 días (rango: 1-25). En el momento de la admisión, los datos clínicos fueron: fiebre (11/12), vómitos (9/12) y dolor de cabeza (8/12). También mostraron mal estado general, 12/12; otitis media aguda, 7/12; y paresia del VI par craneal, 5/12. La punción lumbar fue patológica en 4/12. El microorganismo más frecuentemente aislado fue Streptococcus spp. Se confirmaron mutaciones protrombóticas en 2/12. La tomografía computarizada craneal permitió el diagnóstico en 9/12; la resonancia magnética lo logró en 12/12. Los signos neurológicos anteriores o el tiempo de diagnóstico no influyeron en la aparición de otras complicaciones de la imagen. Recibieron tratamiento antibiótico 12/12; heparina, 10/12; y cirugía, 11/12. No hubo secuelas. Conclusión: En nuestra serie, la otitis, el dolor de cabeza, los vómitos y la fiebre fueron frecuentes. Las pruebas complementarias permitieron el diagnóstico de sospecha, pero el diagnóstico definitivo se obtuvo por neuroimagen. No hubo secuelas y las terapias fueron principalmente antibióticos de amplio espectro, heparina y cirugía.(AU)

Introduction: Septic thrombosis of intracranial venous sinuses (STSV) is a rare and severe complication of cranial infections. Materials and methods: The main objective of this paper is to describe the clinical data, diagnostic procedures, treatment and evolution of a series of cases of STSV. In addition, the current literature is reviewed. Observational retrospective study by review of medical histories (January 1995-December 2016). The data collected were: clinical, analytical, epidemiological, microbiological, radiological, management and follow-up. A descriptive and statistical analysis of the data was done. Results: Twelve children were included (86,832 admissions studied). They have a median age of 4.5 years (range 1-13) with a median time of symptoms of 6 days (range 1-25). At admission, the clinical data were: fever (11/12), vomiting (9/12) and headache (8/12). They also showed bad general status 12/12, 7/12 acute otitis media and 5/12 VI cranial nerve paresis. The lumbar puncture was pathological in 4/12. The most frequently microorganism isolated was Streptococcus sp. Prothrombotic mutations were confirmed on 2/12. Cranial computed tomography allowed diagnosis in 9/12; the magnetic resonance imaging achieves that in 12/12. Previous neurological signs or time to diagnosis did not influence the appearance of other image complications. All received antibiotic treatment, heparin 10/12 and 11/12 surgery. There were no sequels. Conclusion: In our series otitis, headache, vomiting and fever were prevalent. Complementary tests allowed the suspect but the definitive diagnosis was obtained by neuroimaging. There were no sequels and the therapies were mainly wide broad-spectrum antibiotics, heparin, and surgical.(AU)

Neonato con sobreinfección de un cefalohematoma complicado con meningitis: a propósito de un caso / Newborn with infected cephalohematoma complicated with meningitis: report of one case

INTRODUCCIÓN: La infección del cefalohematoma es una patología muy infrecuente, aunque potencialmente grave por las complicaciones asociadas que puede conllevar: osteomielitis del hueso subyacente, meningitis o sepsis. CASO CLÍNICO: Se expone un caso de una recién nacida por cesárea con antecedente de atresia duodenal intervenida, que desarrolla, al octavo día de vida, la infección de un cefalohematoma con cuadro séptico y meningitis asociada. Tras un drenaje del cefalohematoma y la administración de antibioterapia durante 3 semanas, la paciente evoluciona favorablemente. CONCLUSIÓN: Ante la sospecha de la infección de un cefalohematoma, el drenaje del mismo es la clave diagnóstica y terapéutica, ya que la antibioterapia de forma aislada puede no ser suficiente para erradicar el patógeno. Se deben descartar otras complicaciones asociadas, como meningitis, sepsis u osteomielitis del hueso subyacente

INTRODUCTION: The infection of a cephalohematoma is an infrequente but potentially fatal condition due to its possible complications such as osteomyelitis, meningitis or sepsis. CASE REPORT: The report describes a newborn delivered by cesarean section, and a history of duodenal atresia with surgical correction, who develops, at 8 days of life, an infection of a cephalohematoma with sepsis and meningitis. After aspiration of the cephalohematoma and a three week course of antibiotics, she showed a favorable outcome. CONCLUSION: When the infection of a cephalohematoma is suspected, its drainage is both a diagnostic and therapeutic tool, as antibiotic therapy alone is often insufficient. Possible complications such as meningitis, osteomyelitis and sepsis must be ruled out

A Comparison of Mechanical Properties of Different Hydroxyapatite (HAp) Based Nanocomposites: The Influence of Morphology and Preferential Orientation.

Three different types of hydroxyapatite (HAp) based porous ceramic materials were obtained through the modified gel casting method; one of them was made of commercial HAp particles and used as a reference in the mechanical characterization. Other type of ceramic was elaborated using HAp nanofibers, which were synthesized through the microwave assisted hydrothermal method and they possess a high crystallinity, purity and a preferential crystalline orientation in the [300], such were grown along the [001]. The third type of porous ceramic was elaborated using a combination of HAp nanofibers and particles. The HAp nanofibers and particles were previously analyzed by using X-ray diffraction to study their crystal structure, the topology and morphology of those HAp aggregates were observed with scanning electron microscopy (SEM); high-resolution transmission electron microscopy was useful to carry out a detailed crystallographic analysis. Afterwards, an organic phase made of gelatin was added to the porous ceramics in order to obtain nanocomposite materials. Two different concentrations of gelatin were used separately, and the combination of three types of porous ceramics and two concentrations of gelatin produced six different nanocomposite materials. All of these composite materials were observed through the SEM to see their topology and porosity and after that, they were probed under compression tests and their corresponding mechanical behavior was analyzed. All the composites showed mechanical properties similar to those observed in cellular materials. The Young modulus and ultimate strength were compared, finally, it was determined the contribution to the mechanical properties of the morphology, crystalline quality and preferential crystalline orientation in the HAp nanofibers. According to such properties, the composite material made of HAp nanofibers has bone tissue implant potential applications.

Study of paediatric patients with the clinical and biochemical phenotype of glucose transporter type 1 deficiency syndrome. / Estudio de pacientes pediátricos con fenotipo clínico y bioquímico de síndrome de déficit de transportador de glucosa cerebral (GLUT-1).

INTRODUCTION: Glucose transporter type 1 (GLUT1) deficiency syndrome may present a range of phenotypes, including epilepsy, intellectual disability, and movement disorders. The majority of patients present low CSF glucose levels and/or defects in the SLC2A1 gene; however, some patients do not present low CSF glucose or SLC2A1 mutations, and may have other mutations in other genes with compatible phenotypes. AIMS: We describe the clinical, biochemical, and genetic characteristics of the disease and perform a univariate analysis of a group of patients with clinical and biochemical phenotype of GLUT1 deficiency syndrome, with or without SLC2A1 mutations. MATERIAL AND METHODS: The study included 13 patients meeting clinical and biochemical criteria for GLUT1 deficiency syndrome. SLC2A1 sequencing and multiplex ligation-dependent probe amplification were performed; exome sequencing was performed for patients with negative results. RESULTS: Six patients presented the classic phenotype; 2 paroxysmal dyskinesia, 2 complex movement disorders, 2 early-onset absence seizures, and one presented drug-resistant childhood absence epilepsy. Six patients were positive for SLC2A1 mutations; in the other 5, another genetic defect was identified. No significant differences were observed between the 2 groups for age of onset, clinical presentation, microcephaly, intellectual disability, or response to ketogenic diet. Patients with SLC2A1 mutations presented more clinical changes in relation to diet (66.7% vs. 28.6% in the SLC2A1-negative group) and greater persistence of motor symptoms (66% vs. 28.6%); these differences were not statistically significant. Significant differences were observed for CSF glucose level (34.5 vs. 46mg/dL, P=.04) and CSF/serum glucose ratio (0.4 vs. 0.48, P<.05). CONCLUSIONS: GLUT1 deficiency syndrome may be caused by mutations to genes other than SLC2A1 in patients with compatible phenotype, low CSF glucose level, and good response to the ketogenic diet.

Antibacterial activity of amoxicillin in vitro and its oral bioavailability in broiler chickens under the influence of 3 water sanitizers.

The interaction of 3 water sanitizers (sodium hypochlorite, iodine-polyvinylpyrrolidone, and citrate) utilized in poultry production on antibacterial activity and bioavailability of amoxicillin trihydrate (AMX) were studied. Sanitizers were mixed with AMX in prepared water, the resulting substances were regarded as amoxicillin-sanitizer products (ASP). First, the in vitro antibacterial activity of each ASP was compared to that of AMX. Then, pharmacokinetics (PK) of ASP and AMX diluted in prepared water, were carried out in broiler-chickens. Amoxicillin or ASP (20 mg/kg) from different concentrations of sanitizers was directly placed into the chicken's crop and blood samples were taken. Basic PK parameters were obtained. Serum activity/concentrations of AMX were assessed by agar diffusion and corroborated with high performance liquid chromatography. Results show that ASP of AMX/sodium hypochlorite decrease both, the antimicrobial activity of in vitro AMX and its relative bioavailability (Fr) assessed with the maximum serum concentration (Cmax), the area under the concentration-time curve, and the mean residence time (MRT) (3.80 µg/mL, 2.70 µg/mL·h, and 0.59 h, respectively), compared to the AMX administered alone (12.54 µg/mL, 44.02 µg/mL·h, and MRT 2.78 h). ASP from amoxicillin/ionophore, reduced the Cmax (10.62 µg/mL), Fr (94.67%), and MRT (2.07 h), at the highest tested concentrations. In contrast, the 2 highest concentrations of the citrate sanitizer increased the Cmax (15.07 and 15.47 µg/mL), Fr (119 and 132%), and MRT (3.32 and 4.06 h) and their in vitro antimicrobial activity. Interactions between the tested water sanitizers and AMX modify the Cmax, Fr, MRT of the latter, altering the PK/pharmacodymanic ratios for a time-dependent antibiotic. Results also reveal that the use of amoxicillin trihydrate administered through the drinking water does not meet the required PK/pharmacodymanic ratios. Thus, it is here postulated that this antibiotic should be administered at least twice a day and that its interaction with water sanitizers should be considered.

Multi-center analysis of the effect of T-cell acute lymphoblastic leukemia subtype and minimal residual disease on allogeneic stem cell transplantation outcomes.

This study aims to provide a detailed analysis of allogeneic stem cell transplantation (allo-SCT) outcomes in a large T-cell acute lymphoblastic leukemia (T-ALL) cohort with a specific emphasis on the effects of pre-transplant minimal residual disease (MRD) and disease subtype, including the aggressive early-thymic precursor (ETP) subtype. Data from 102 allo-SCT patients with a diagnosis of T-ALL from three centers were retrospectively analyzed. Patients were grouped into four T-ALL subtypes: ETP, early, cortical and mature. At 3 years, overall survival (OS), PFS, non-relapse mortality and cumulative incidence (CI) progression were 35, 33, 11 and 55%, respectively. Patients transplanted in first complete remission (CR1) had a 3-year OS of 62% versus those transplanted in CR2 or greater (24%) (hazards ratio 1.6, P=0.2). Patients with MRD positivity at the time of transplant had significantly higher rates of progression compared with those with MRD negativity (76 vs 34%, hazards ratio 2.8, P=0.006). There was no difference in OS, PFS or cumulative incidence (CI) progression between disease subtypes, including ETP (n=16). ETP patients transplanted in CR1 (n=10) had OS of 47%, comparable to other disease subtypes, suggesting that allo-SCT can overcome the poor prognosis associated with ETP. MRD status at transplant was highly predictive of disease relapse, suggesting novel therapies are necessary to improve transplant outcomes.

Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL.

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.

Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors.

BACKGROUND: High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. PATIENTS AND METHODS: Eligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ≤ 1.8 mg/dl and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-year relapse-free survival (RFS) from an expected 25% 2-year RFS in this population. RESULTS: We enrolled 43 male patients, median age 30 (20-49) years, with absolute refractory (N = 20), refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1-5) prior relapses. Disease status right before HDC was unresponsive (N = 24, progressive disease 22, stable disease 2), partial response with positive markers (PRm(+)) (N = 8), PRm(-) (N = 7) or complete response (N = 4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively. CONCLUSIONS: Sequential bevacizumab/GemDMC-bevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population. CLINICALTRIALSGOV: NCT00936936.

Informed consent in colonoscopy: A comparative analysis of 2 methods.

BACKGROUND: The manner in which informed consent is obtained varies. The aim of this study is to evaluate the level of knowledge about colonoscopy and comparing 2 methods of obtaining informed consent. MATERIALS AND METHODS: A comparative, cross-sectional, observational study was conducted on patients that underwent colonoscopy in a public hospital (Group A) and in a private hospital (Group B). Group A received information verbally from a physician, as well as in the form of printed material, and Group B only received printed material. A telephone survey was carried out one or 2 weeks later. RESULTS: The study included a total of 176 subjects (group A [n=55] and group B [n=121]). As regards education level, 69.88% (n=123) of the patients had completed university education, 23.29% (n= 41) secondary level, 5.68% (n=10) primary level, and the remaining subjects (n=2) had not completed any level of education. All (100%) of the subjects knew the characteristics of the procedure, and 99.43% were aware of its benefits. A total of 97.7% received information about complications, 93.7% named some of them, and 25% (n=44) remembered major complications. All the subjects received, read, and signed the informed consent statement before the study. There were no differences between the groups with respect to knowledge of the characteristics and benefits of the procedure, or the receipt and reading of the consent form. Group B responded better in relation to complications (P=.0027) and group A had a better recollection of the major complications (P<.0001). Group A had a higher number of affirmative answers (P<.0001). CONCLUSIONS: The combination of verbal and written information provides the patient with a more comprehensive level of knowledge about the procedure.

Comparison of outcomes at two institutions of patients with ALL receiving ex vivo T-cell-depleted or unmodified allografts.

We compared outcomes of adult patients receiving T-cell-depleted (TCD) hematopoietic SCT (HCT) without additional GVHD prophylaxis at Memorial Sloan Kettering Cancer Center (MSKCC, N=52), with those of patients receiving conventional grafts at MD Anderson Cancer Center (MDACC, N=115) for ALL in CR1 or CR2. Patients received myeloablative conditioning. Thirty-nine patients received anti-thymocyte globulin at MSKCC and 29 at MDACC. Cumulative incidence of grades 2-4 acute (P=0.001, 17.3% vs 42.6% at 100 days) and chronic GVHD (P=0.006, 13.5% vs 33.4% at 3 years) were significantly lower in the TCD group. The non-relapse mortality at day 100, 1 and 3 years was 15.4, 25.0 and 35.9% in the TCD group and 9.6, 23.6 and 28.6% in the unmodified group (P=0.368). There was no difference in relapse (P=0.107, 21.3% vs 35.5% at 3 years), OS (P=0.854, 42.6% vs 43.0% at 3 years) or RFS (P=0.653, 42.8% vs 35.9% at 3 years). In an adjusted model, age >50, cytogenetics and CR status were associated with inferior RFS (hazard ratio (HR)=2.16, P=0.003, HR=1.77, P=0.022, HR=2.47, P<0.001), whereas graft type was NS (HR=0.90, P=0.635). OS and RFS rates are similar in patients undergoing TCD or conventional HCT, but TCD effectively reduces the rate of GVHD.

Intravenous BU plus Mel: an effective, chemotherapy-only transplant conditioning regimen in patients with ALL.

We investigated the administration of i.v. BU combined with melphalan (Mel) in patients with ALL undergoing allogeneic hematopoietic SCT. Forty-seven patients with a median age of 33 years (range 20-61) received a matched sibling (n=27) or matched unrelated donor transplant (n=20) for ALL in first CR (n=26), second CR (n=13), or with more advanced disease (n=8). BU was infused daily for 4 days, either at a fixed dose of 130 mg/m² (5 patients) or using pharmacokinetic (PK) dose adjustment (42 patients), to target an average daily area-under-the-curve (AUC) of 5000 µmol/min, determined by a test dose of i.v. BU at 32 mg/m². This was followed by a rest day, then two daily doses of Mel at 70 mg/m². Stem cells were infused on the following day. The 2-year OS, PFS and non-relapse mortality (NRM) rates were 35% (95% confidence interval (CI), 23-51%), 31% (95% CI, 21-48%) and 37% (95% CI, 23-50%), respectively. Acute NRM at 100 days was favorable at 12% (95% CI, 5-24%); however, the 2-year NRM was significantly higher for patients older than 40 years, 58% vs 20%, mainly due to GVHD.

Clofarabine combined with busulfan provides excellent disease control in adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation.

We investigated the safety and early disease control data for i.v. busulfan (Bu) in combination with clofarabine (Clo) in patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation (SCT). Fifty-one patients (median age, 36 years; range, 20-64 years) received a matched sibling (n = 24), syngeneic (n = 2), or matched unrelated donor transplant (n = 25) for acute lymphoblastic leukemia in first complete remission (n = 30), second complete remission (n = 13), or active disease (n = 8). More than one-half of the patients had a high-risk cytogenetic profile, as defined by the presence of t(9;22) (n = 17), t(4;11) (n = 3), or complex cytogenetics (n = 7). Clo 40 mg/m(2) was given once daily, with each dose followed by pharmacokinetically dosed Bu infused over 3 hours daily for 4 days, followed by hematopoietic SCT 2 days later. The Bu dose was based on drug clearance, as determined by the patient's response to a 32-mg/m(2) Bu test dose given 48 hours before the high-dose regimen. The target daily area under the receiver-operating characteristic curve was 5500 µM/min for patients age <60 years and 4000 µM/min for those age ≥60 years. The regimen was well tolerated, with a 100-day nonrelapse mortality rate of 6%. With a median follow-up of 14 months among surviving patients (range, 6-28 months), the 1-year overall survival, disease-free survival, and nonrelapse mortality rates were 67% (95% confidence interval [CI], 55%-83%), 54% (95% CI, 41%-71%), and 32% (95% CI, 16%-45%), respectively. For patients undergoing SCT in first remission, these respective rates were 74%, 64%, and 25%. Our data indicate that the combination of Clo and Bu provides effective disease control while maintaining a favorable safety profile.

Efecto del pulido radicular en la adhesion dentinaria: estudio al microscopio electronico de barrido (MEB) / Effects of the root planning in the dentin adhesi¨®n: a SEM study

Para analizar al MEB las características micro morfológicas de la adhesión dentinaria en superficies radiculares expuestas a enfermedad periodontal y tratadas con pulido radicular, se utilizaron 30dientes, separados en tres grupos: Grupo 1: Dientes con enfermedad periodontal tratados solo con pulido radicular. Grupo 2: Dientes con enfermedad periodontal tratados con pulido radicular y sometidas a grabado con ácido fosfórico al 34% por dos minutos. Grupo 3: Dientes con enfermedad periodontal tratados con pulido radicular, en las cuales se realizó todo el protocolo adhesivo para confeccionar resinas compuestas. Resultados. Grupo 1: Se observó una capa de barro dentinario en toda la superficie. Grupo 2: Presentaba una irregular capa de barro dentinario. Grupo 3: Se observó una seudocapa hibrida de 15,9 um de grosor, pero no se evidencio la presencia de tags deresina. Conclusiones. La adhesión en raíces con enfermedad periodontal y tratadas con pulidoradicular se realiza sobre barro dentinario que no es removido por la acción del ácido fosfórico, no formándose capa hibrida ni tags de resina, por lo tanto creemos que la adhesión como concepto propiamente tal no existe en estos tejidos (AU)

The aim of this in vitro study was to analize some characteristics of dentinary adhesion over root surfaces exposed to periodontal disease an treated with root planning by observing the samples at SEM. 30 teeth were classified in three groups. Group 1: Teeth with periodontal disease treated only by root planning. Group 2: Teeth with periodontal disease treated by root planning and 34% fosforic acid etching. Group 3: Teeth with periodontal disease treated by root planning at and an adhesive composite restoration. Results: Group 1 presented a thick smear layer over all the treated surface. Group 2 presented an irregular adhesive layer. Group 3 showed a 15.9 µm thick layer that looks as an hybrid layer, composite tags were not found in this group. Conclusions: Dentine adhesion over teeth with periodontal disease and treated by root planning is achieved over a thick smear layer, which is not removed by fosforic acid. Hybrid layer and composite tags were not formed, so it is assumed that adhesion does not occur (AU)

[n-3 fatty acid evaluation in eighteen Mexican marine fishes as functional food]. / Evaluación de los acidos grasos n-3 de 18 especies de pescados marinos mexicanos como alimentos funcionales.

The objective of the present work was to characterize the n-3 fatty acid composition of eighteen species of Mexican marine fishes and to evaluate their potential as functional food. Total lipids and fatty acid (FA) compositions were obtained of the edible portion of the fish, by solvent extraction and gas chromatography. Fifty percent of the studied species proceeded of the Mexican Pacific and the remainder from the Gulf of Mexico. The total lipid content varied from 0.76 to 7.13 g/100g. Averages of 58.51, 58.74 and 132.85 mg/100g of flesh were obtained for saturated, monounsaturated and polyunsaturated FA, respectively. In all the samples the n-3 fatty acids identified in order of abundance were (mg/100g), C22:6n-3 (DHA) (85.02), C20:5 n-3 (EPA)(16.22), C18:3 n-3 (ALA)(1.95) and the C20:3 n-3 was found only in four species (range from 0.08 to 12.99 mg/100g). Twenty-seven percent of the fishes exhibited low (4 to 40), 66% intermediate (70 to 170) and 7% high values (200 to 300 mg/100g) of n-3 FA. The latter species were identified as picuda (Sphyraena agentea) and sargo (Lagodon rhomboides). Since international standards recommend a daily regular consumption form 200 to 650 mg of EPA + DHA/day as beneficial for good health, it is therefore suggested as functional food.

Evaluación de los acidos grasos n-3 de 18 especies de pescados marinos mexicanos como alimentos funcionales / n-3 fatty acid evaluation in eighteen Mexican marine fishes as functional food

The objective of the present work was to characterize the n-3 fatty acid composition of eighteen species of Mexican marine fishes and to evaluate their potential as functional food. Total lipids and fatty acid (FA) compositions were obtained of the edible portion of the fish, by solvent extraction and gas chromatography. Fifty percent of the studied species proceeded of the Mexican Pacific and the remainder from the Gulf of Mexico. The total lipid content varied from 0.76 to 7.13 g/100g. Averages of 58.51, 58.74 and 132.85 mg/100g of flesh were obtained for saturated, monounsaturated and polyunsaturated FA, respectively. In all the samples the n-3 fatty acids identified in order of abundance were (mg/100g), C22:6n-3 (DHA) (85.02), C20:5 n-3 (EPA)(16.22), C18:3 n-3 (ALA)(1.95) and the C20:3 n-3 was found only in four species (range from 0.08 to 12.99 mg/100g). Twenty-seven percent of the fishes exhibited low (4 to 40), 66% intermediate (70 to 170) and 7% high values (200 to 300 mg/100g) of n-3 FA. The latter species were identified as picuda (Sphyraena agentea) and sargo (Lagodon rhomboides). Since international standards recommend a daily regular consumption form 200 to 650 mg of EPA + DHA/day as beneficial for good health, it is therefore suggested as functional food.

Absceso cerebral / Brain abscess

El absceso cerebral es una patología poco frecuente en la infancia, aunque grave, que puede presentar una alta morbimortalidad, a pesar de los avances diagnósticos y terapéuticos actuales. El germen causal depende de los factores predisponentes. La presentación clínica en niños es inespecífica, y requiere la sospecha precoz por parte del médico. La tomografía computarizada (TC) y/o la resonancia magnética (RM) son herramientas indispensables para realizar el diagnóstico de certeza. El tratamiento de la mayoría de los abscesos consiste en antibioterapia de amplio espectro y drenaje quirúrgico, aunque en la fase precoz de cerebritis puede responder sólo a tratamiento médico. Describimos una niña de 13 años diagnosticada de dos abscesos cerebrales originados a partir de una otitis media y que se encontraba en tratamiento antibiótico. Presentaba cefalea, vómitos y otalgia a su ingreso. El diagnóstico se hizo mediante TC. Se trató con antibioterapia de amplio espectro con buna penetración cerebral, con la que evolucionó a un aumento del tamaño del absceso y un empeoramiento clínico. Se realizó la aspiración estereotáxica de la lesión y la evolución fue favorable sin complicaciones postquirúrgicas (AU)

Brain abscess is uncommon but life- threatening infection in children with high mobility and mortality despite recent advances in diagnostic and therapeutic modalities. Predominant etiologic microorganisms vary depending on these predisposing factors. The clinical presentation in children can be nonspecific, and a high index of suspicion is required. Computed tomography (CT) and/or magnetic resonance imaging (MRI) are essential tools that enable the physician to diagnosis. Surgical drainage with antimicrobial therapy is the treatment of choice for most brain abscesses. In the early phase of cerebritis, infection can respond to long-term antibiotic therapy alone. We described a 13 years old girl with two brain abscesses originated form otitis media with antibiotic therapy. Diagnosis was given by CT. Initial treatment with broad spectrum antibiotics with good cerebral penetration was associated with an increase in the size of abscess and clinical worsening. Stereotactic aspiration of lesion and culture was performed and the patient showed improvement and there was any postoperative complication (AU)