Switching from onabotulinum toxin A to abobotulinum toxin A for treating detrusor overactivity in spinal cord injured patient, does it really work?

AIM: To assess the efficacy of switching to Abobotulinumtoxin A (ATA) intradetrusor injections (IDI) after failure of Onabotulinumtoxin A (OTA) IDI for the treatment of neurogenic detrusor overactivity in patients with spinal cord injury (SCI). MATERIALS AND METHODS: A single-centre retrospective chart review study. All SCI patients who started OTA IDI after 2011 and had an ATA IDI switch were included. The primary outcome was the clinical and urodynamic efficacy of the switch to ATA IIDs at the last follow-up. Secondary outcomes were initial efficacy, duration of ATA treatment, and patient outcome including the occurrence of augmentation enterocystoplasty at last follow-up. RESULTS: Sixty-two patients were included. Eighteen patients (28.9%) were initially responders to ATA IDI. Nine patients (14.5%) remained responders at last follow-up after a median of 17 months (AE 8.8-29). Thirty-two patients (51.6%) had had or were awaiting augmentation enterocystoplasty with a follow-up time of 18.5 months (IQR 8-27). Eleven patients (17.7%) were on ATA IDI with low efficacy. Seven patients (11.3%) were switched back to OTA and 3 patients (4.8%) changed their voiding pattern. CONCLUSION: Switching from OTA to ATA toxin for IDI in the treatment of detrusor overactivity after spinal cord injury have long-term efficacy for a limited number of patients but may delay the need for surgery.

Efficacy and Tolerance of Carboplatin plus Cetuximab (Simplified EXTREME Regimen) in Patients with Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma.

AIMS: The EXTREME regimen is the standard for recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC). However, many patients have a poor performance status and/or comorbidities, making them unfit for this regimen. We have treated them with carboplatin and cetuximab (simplified EXTREME regimen) since 2007. Our aim was to assess the efficacy and tolerance of this regimen in this frail population. MATERIALS AND METHODS: A retrospective chart review of all patients treated with the simplified EXTREME regimen for recurrent and/or metastatic HNSCC in three academic hospitals between 2007 and 2017 was carried out. The primary end point was overall survival. Secondary end points were progression-free survival (PFS), overall response rate (ORR) and toxicity. RESULTS: One hundred and three patients were included. The median age was 63 years, 40% had performance status 2-3. The median follow-up was 30.2 months. The median overall survival and PFS were 7.2 and 3.7 months, respectively. The median overall survival was 10.1 months in patients with performance status 0-1 versus 4.6 months in patients with performance status 2-3 (P = 0.01). ORR was 39%. Acute grade 3-4 haematological and non-haematological toxicity rates were 25.2% and 27.2%, respectively. Patients with grade 1 or more skin toxicity had a higher ORR (hazard ratio = 3.44; P = 0.03), a prolonged overall survival (hazard ratio = 0.37; P < 0.0001) and PFS (hazard ratio = 0.29; P < 0.0001). During treatment, 29% of patients had pain reduction, 13.5% had weight gain and 17.2% had an improvement in performance status. CONCLUSIONS: This is the largest cohort of patients treated with simplified EXTREME for HNSCC. It was well tolerated, with a high ORR. Interestingly, skin toxicity correlated with treatment efficacy.

Vitamin D and iron deficiencies in children and adolescents with cerebral palsy. / Deficiencia de vitamina D y de hierro en niños y adolescentes con parálisis cerebral.

INTRODUCTION: Children and adolescents with cerebral palsy (CP) are at a greater risk of malnutrition and micronutrient deficiencies. Two deficiencies that we can study and treat are vitaminD (VD) and iron deficiencies; however, no studies have described these deficiencies in Chile. OBJECTIVE: To describe the status of VD and iron in patients with CP and evaluate the relationship with certain factors associated with deficiencies of these micronutrients. PATIENTS AND METHOD: We performed a descriptive, cross-sectional study including 69 patients aged between 2 and 21years, from two public hospitals. Data were obtained on demographic variables, motor function, use of feeding tube, and pharmacological treatment. We performed a nutritional assessment according to patterns of CP and determined 25-hydroxyvitaminD (25[OH]D) ferritin, and albumin levels. RESULTS: Patients' mean age was 11.1±4.9years; 43 (62.3%) were male; and 56 (81.2%) had moderate-to-severe CP. Thirty-five (50.7%) used a nasogastric tube and/or gastrostomy; 15.4% were underweight and 73.8% were eutrophic, all with normal height. Twenty (29%) and 4 patients (6.2%) received VD and iron supplementation, respectively. Albuminaemia was normal in all patients. Mean 25(OH)D level was 24.3±8.8ng/mL; 33 patients (47.8%) had insufficiency and 21 (30.4%) deficiency; 36 patients (52.2%) had low ferritin levels. There was no association between 25(OH)D level and the other variables studied. Low ferritin levels were found to be associated with older age (P=.03), being male (P=.006), and feeding tube use (P=.006). CONCLUSIONS: The patients studied mainly had moderate-to-severe CP, with a high frequency of suboptimal VD values and low plasma ferritin; few patients received VD and/or iron supplementation. We suggest monitoring 25(OH)D and ferritin levels due to the high rate of deficiency of these nutrients; public hospitals should be equipped with drugs to treat these deficiencies.

High prevalence of Mycoplasma genitalium infection and macrolide resistance in patients enrolled in HIV pre-exposure prophylaxis program.

OBJECTIVES: Limited data on Mycoplasma genitalium infection has been reported among PrEP users. The aim of this study was to estimate the prevalence and macrolide resistance of M. genitalium infection among enrollees in a French PrEP program. PATIENTS AND METHODS: M. genitalium infection screening was systematically and prospectively proposed to patients of the Bordeaux PrEP program (between January 2016 and February 2017). Macrolide resistance was evaluated in M. genitalium-positive patients. RESULTS: Among 89 clients, M. genitalium infection prevalence was 10% (mainly asymptomatic) with a high rate of macrolide resistance (58%). CONCLUSIONS: Because of a high level of macrolide resistance, a systematic search for M. genitalium macrolide resistance associated-mutations may be recommended in PrEP users before initiating the antibiotic therapy.

Generation of Mycoplasma hominis gene-targeted mutants by targeting-induced local lesions in genomes (TILLING).

BACKGROUND: Mycoplasma hominis is a human urogenital pathogen involved in gynaecological, neonatal and extra-genital infections. However, no versatile genetic tools are currently available to study the pathogenicity of this bacterium. Targeting-Induced Local Lesions IN Genomes (TILLING) is a reverse-genetic method that combines point mutations induced by chemical mutagenesis with a DNA screening technique. We used ethyl methanesulfonate (EMS) that introduces C-G to T-A transition mutations to generate a library of M. hominis mutants. As a proof of concept, mutagenized organisms were screened for mutations in two target genes previously associated with the mycoplasma pathogenicity, the vaa gene encoding an adhesin lipoprotein and the oppA gene encoding the main ectoATPase of the bacterium. The resulting mutants were evaluated using functional assays, an adhesion to HeLa cell assay for vaa-mutants and an ATPase activity test for oppA-mutants. RESULTS: A 1200-clone library was generated by exposing M. hominis PG21 to 9 mg/mL EMS for 3 h. To identify mutants of interest, targeted gene fragments were amplified, heat-denatured, slowly reannealed and digested with the mismatch-specific endonuclease ENDO1. If multiple alleles were present in the PCR amplicons, these alleles formed heteroduplexes during reannealing that were specifically cleaved by ENDO1 at mismatching positions. A total of four vaa-mutants and two oppA-mutants harbouring missense mutations were obtained and fully sequenced. Zero to eight additional mutations were identified in the genomes of each mutant. The vaa-mutants were tested for adhesion to immobilized HeLa cells but their adhesion was not significantly different from the adhesion of M. hominis PG21. One of the two oppA-mutants that were tested for ATPase activity presented a higher affinity for its ATP substrate than the parental strain. CONCLUSION: For the first time, we demonstrated that M. hominis gene-targeted mutants could be successfully obtained using this TILLING strategy. In the absence of robust genetic tools for studying M. hominis, the TILLING strategy that can target any gene of the genome could help to elucidate gene functions and to better understand the pathogenesis of this human pathogenic species.

Nutritional recovery after cardiac surgery in children with congenital heart disease. / Recuperación nutricional post cirugía cardiaca en niños con cardiopatía congénita.

INTRODUCTION: Malnutrition is common in children with congenital heart disease (CHD). Medical treatment and surgical interventions contribute improving the nutritional status of these children. OBJECTIVE: To describe nutritional recovery in children with CHD and associated factors after surgery. PATIENTS AND METHOD: Longitudinal study. 46 Children under 18 years old admitted for CHD surgery between April 2015 and April 2016 were recruited. The following CHD were included: Ventricular septal defect (VSD), Atrial septal defect (ASD), Hypoplastic left heart syndrome (HLHS), Tetralogy of Fallot (TOF), and Transposition of great arteries (dTGA). Children with genetic syndromes and other diseases that could compromise nutritional status were excluded. We obtained demographic, CHD, nasogastric tube use (NGT), nutritional evaluation, and weight and height data at the time of admission and one, three and six months after surgery and. Z-score to assess anthropometric measu res were calculated according to WHO standards. RESULTS: Median age was 8 months (IQR: 3,26), 24 (52%) male, 6 (13%) preterm and 12 (26,1%) small for gestational age (SGA). CHD diagnosis were: 9 (19,6%) VSD, 8 (17,4%) ASD, 12 (26,1%) HLHS, 9 (19,6%) TOF and 8 (17,4%) dTGA. The mean weight-for-heigth-BMI-for-age-z-score (W/H-BMI/AZ) was 0,6 ± 1,5 SD, (28.3% of undernutri tion). The mean heigth-for-age-z-score (H/AZ) was -0,86 ± 1.3sd (21.7% of short stature). We found differences between each CHD and age, use of NGT and been under nutritional follow-up. There was an improvement between H/AZ at admission and 3rd month (p = 0,02), and W/H-BMI/AZ at 3th (p = 0,046) and 6th month (p = 0,001). Use of NGT decreased from admission to 6th month (19 vs 3) (p = 0,0016). We found correlation between admission W/H-BMI/AZ and nutritional recovery (r = -0,7; p < 0,001). CONCLUSION: There is a high prevalence of prematurity, SGA, undernutrition and short stature use of with weight recovery but not in heigth after cardio-surgery.

Recuperación nutricional post cirugía cardiaca en niños con cardiopatía congénita / Nutritional recovery after cardiac surgery in children with congenital heart disease

Resumen: Introducción: La desnutrición es frecuente en niños con cardiopatía congénita (CC). El manejo mé dico e intervenciones cardioquirúrgicas contribuyen a mejorar el estado nutricional en estos niños. Objetivo: Describir la recuperación nutricional posterior a cirugía de CC y sus factores asociados. Pacientes y Método: Estudio longitudinal. Se reclutaron 46 sujetos menores de 18 años ingresados para cirugía de CC entre abril de 2015 y abril de 2016. Se incluyeron las siguientes CC: comunica ción interventricular (CIV), comunicación interauricular (CIA), hipoplasia de ventrículo izquierdo (HVI), Tetralogía de Fallot (TOF) y transposición de grandes arterias (dTGA). Se excluyeron los síndromes genéticos y pacientes con otra enfermedad con compromiso nutricional. Se obtuvo al ingreso y los meses 1, 3 y 6 postquirúrgico los datos demográficos, de su CC, uso de sonda naso- gástrica (SNG), control nutricional, peso y talla. Los valores Z de indicadores antropométricos se calcularon según estándares de la OMS. Resultados: La mediana de edad de los pacientes reclutados fue de 8 meses (RIC 3,26); 24 (52%) varones; 6 (13%) prematuros y 12 (26,1%) pequeños para edad gestacional (PEG). Las CC fueron: 9 (19,6%) CIV; 8 (17,4%) CIA; 12 (26,1%) HVI; 9 (19,6%) TOF y 8 (17,4%) dTGA. ZP/T-IMC/E promedio -0,6 (± 1,5DE), 28,3% malnutrición por déficit. ZT/E promedio -0,86 (± 1,3 DE), 21,7% talla baja. Se encontraron diferencias según CC para edad, uso de SNG y tener control nutricional. Hubo una mejoría de ZT/E entre ingreso y tercer mes (p = 0,02) y de ZP/T-IMC/E al tercer (p = 0,046) y sexto mes (p = 0,001). Se disminuyó el uso de SNG, 19 al ingreso y 3 al sexto mes (p = 0,0016). Se encontró una correlación entre ZP/T-IMC/E de ingreso y una recuperación nutricional (r = -0,7; p < 0,001). Conclusiones: En este estudio se encontró una alta prevalencia de prematurez, PEG, malnutrición por déficit y talla baja, con recuperación de peso, pero no de talla post cardiocirugía.

Abstract: Introduction: Malnutrition is common in children with congenital heart disease (CHD). Medical treatment and surgical interventions contribute improving the nutritional status of these children. Objective: To describe nutritional recovery in children with CHD and associated factors after surgery. Patients and Method: Longitudinal study. 46 Children under 18 years old admitted for CHD surgery between April 2015 and April 2016 were recruited. The following CHD were included: Ventricular septal defect (VSD), Atrial septal defect (ASD), Hypoplastic left heart syndrome (HLHS), Tetralogy of Fallot (TOF), and Transposition of great arteries (dTGA). Children with genetic syndromes and other diseases that could compromise nutritional status were excluded. We obtained demographic, CHD, nasogastric tube use (NGT), nutritional evaluation, and weight and height data at the time of admission and one, three and six months after surgery and. Z-score to assess anthropometric measu res were calculated according to WHO standards. Results: Median age was 8 months (IQR: 3,26), 24 (52%) male, 6 (13%) preterm and 12 (26,1%) small for gestational age (SGA). CHD diagnosis were: 9 (19,6%) VSD, 8 (17,4%) ASD, 12 (26,1%) HLHS, 9 (19,6%) TOF and 8 (17,4%) dTGA. The mean weight-for-heigth-BMI-for-age-z-score (W/H-BMI/AZ) was 0,6 ± 1,5 SD, (28.3% of undernutri tion). The mean heigth-for-age-z-score (H/AZ) was -0,86 ± 1.3sd (21.7% of short stature). We found differences between each CHD and age, use of NGT and been under nutritional follow-up. There was an improvement between H/AZ at admission and 3rd month (p = 0,02), and W/H-BMI/AZ at 3th (p = 0,046) and 6th month (p = 0,001). Use of NGT decreased from admission to 6th month (19 vs 3) (p = 0,0016). We found correlation between admission W/H-BMI/AZ and nutritional recovery (r = -0,7; p < 0,001). Conclusion: There is a high prevalence of prematurity, SGA, undernutrition and short stature use of with weight recovery but not in heigth after cardio-surgery.

Diagnóstico nutricional en lactantes menores con cardiopatía congénita: comparación de dos clasificaciones antropométricas / Nutritional assessment in infants with congenital heart disease: comparison of two anthropometric classifications

INTRODUCCIÓN: Los niños con cardiopatía congénita (CC) presentan alto porcentaje de malnutrición por déficit, siendo difícil la interpretación de su estado nutricional. OBJETIVO: Describir el estado nutricional de lactantes con CC utilizando dos clasificaciones antropométricas y realizar una comparación entre ellas. PACIENTES Y MÉTODO: Estudio de cohorte no concurrente. Se estudiaron menores de 12 meses sometidos a cirugía de CC. Se excluyeron prematuros, pequeños para la edad gestacional, portadores de síndrome genético u otra enfermedad con compromiso nutricional. Se registraron datos demográficos, diagnóstico de CC, peso y talla de ingreso. Se realizó evaluación nutricional comparando estándares OMS según clasificación norma ministerial (CNM) y una Clasificación Antropométrica Integrada (CAI) que define desnutrición si (ZT/E)≤-2 y/o (ZP/T)≤-2, riesgo de desnutrición ZP/T entre -1 a -1,9, eutrofia ZP/T entre -0,9 a +0,9, sobrepeso entre +1 a +1,9 y obesidad ZP/T≥+2. RESULTADOS: Se incluyeron 387 intervenciones, 219 (56,6%) varones, mediana de edad 3,1 meses (RIC:0,4;6,4). Un 26,4% tenían talla baja. Utilizando CNM 55 sujetos presentaron dos diagnósticos por superposición de ZP/E y ZP/T, con CAI no hubo superposición. Al comparar CNM con CAI se encontró diferencia en desnutrición 28,9% versus 38,5%(p = 0,001), riesgo de des nutrición 27,4% versus 16,3%(p = 0,01) y obesidad 4,9% versus 3,3%(p = 0,03) respectivamente. Se encontró correlación entre ZP/E y ZP/T, r = 0,6(p < 0,001) y entre ZP/E y ZT/E, r = 0,6(p < 0,001). Conclusiones: Los niños con CC presentan alto porcentaje de desnutrición y talla baja. Utilizando las mismas mediciones antropométricas CAI no presentó superposición de diagnósticos y detectó más desnutrición. El P/E es útil como tamizaje, pero insuficiente en malnutrición crónica.

INTRODUCTION: Children with congenital heart disease (CHD) present a high percentage of undern utrition and the interpretation of their nutritional assessment is difficult. OBJECTIVE: To describe the nutritional status of infants with CHD using two anthropometric classifications and compare them. PATIENTS AND METHOD: Non-concurrent cohort study. We studied children under 12 months under going cardiac surgery. We excluded preterm infants, small for gestational age, carriers of genetic syndrome or other disease with nutritional compromise. Demographic data, type of CHD, weight and height were recorded. Nutritional assessment was performed using WHO standards per health ministry criteria (HMC) and per an Integrated Anthropometric Classification (IAC), which defines undernutrition if height-for-age Z-score (ZT/E)≤-2 and/or weight-for-height (ZP/T)≤-2, risk of un dernutrition as ZP/T between -1 to -1,9, normal as ZP/T between -0.9 to +0.9, overweight as ZP/T between +1 to +1.9 and obesity as ZP/T≥+2. RESULTS: 387 interventions were included, 219 (56.6%) were males, median age 3.1 months (IQR:0.4;6.4). A 26.4% presented short stature. Using HMC classification 55 subjects presented two diagnoses by overlap of ZP/E and ZP/T, although with IAC there was no overlap. Comparing HMC with IAC, a difference was found in undernutrition, 28.9% versus 38.5% (p = 0.001), risk of undernutrition 27.4% versus 16.3%(p = 0.01) and obesity 4.9% ver sus 3.3% (p = 0.03) respectively. Correlation was found between ZP/E and ZP/T, r = 0.6(p < 0.001) and between ZP/E and ZT/E, r = 0.6 (p < 0.001). CONCLUSIONS: Children with CHD have a high per centage of undernutrition and short stature. Using the same anthropometric measurements IAC did not present overlapping diagnoses and detected more undernutrition. P/E is useful as screening, but insufficient in chronic undernutrition.

[Nutritional assessment in infants with congenital heart disease: comparison of two anthropometric classifications]. / Diagnóstico nutricional en lactantes menores con cardiopatía congénita: comparación de dos clasificaciones antropométricas.

INTRODUCTION: Children with congenital heart disease (CHD) present a high percentage of undern utrition and the interpretation of their nutritional assessment is difficult. OBJECTIVE: To describe the nutritional status of infants with CHD using two anthropometric classifications and compare them. PATIENTS AND METHOD: Non-concurrent cohort study. We studied children under 12 months under going cardiac surgery. We excluded preterm infants, small for gestational age, carriers of genetic syndrome or other disease with nutritional compromise. Demographic data, type of CHD, weight and height were recorded. Nutritional assessment was performed using WHO standards per health ministry criteria (HMC) and per an Integrated Anthropometric Classification (IAC), which defines undernutrition if height-for-age Z-score (ZT/E)≤-2 and/or weight-for-height (ZP/T)≤-2, risk of un dernutrition as ZP/T between -1 to -1,9, normal as ZP/T between -0.9 to +0.9, overweight as ZP/T between +1 to +1.9 and obesity as ZP/T≥+2. RESULTS: 387 interventions were included, 219 (56.6%) were males, median age 3.1 months (IQR:0.4;6.4). A 26.4% presented short stature. Using HMC classification 55 subjects presented two diagnoses by overlap of ZP/E and ZP/T, although with IAC there was no overlap. Comparing HMC with IAC, a difference was found in undernutrition, 28.9% versus 38.5% (p = 0.001), risk of undernutrition 27.4% versus 16.3%(p = 0.01) and obesity 4.9% ver sus 3.3% (p = 0.03) respectively. Correlation was found between ZP/E and ZP/T, r = 0.6(p < 0.001) and between ZP/E and ZT/E, r = 0.6 (p < 0.001). CONCLUSIONS: Children with CHD have a high per centage of undernutrition and short stature. Using the same anthropometric measurements IAC did not present overlapping diagnoses and detected more undernutrition. P/E is useful as screening, but insufficient in chronic undernutrition.

Overexpression of a dominant-negative type II TGFbeta receptor tagged with green fluorescent protein inhibits the effects of TGFbeta on cell growth and gene expression of mouse adrenal tumor cell line Y-1 and enhances cell tumorigenicity.

Transforming growth factor beta (TGFbeta) has been reported to be a potent growth inhibitor of epithelial cells. The purpose of the present work was to study in vitro and in vivo the effects of overexpression of a dominant-negative type II TGFbeta receptor on the proliferation and differentiation of Y-1 cells. Stable transfections were performed with a mutant TbetaRII (TbetaRII-KR) fused with the Enhanced Fluorescent Green Protein (EGFP). The expression of this fusion protein and its overexpression were demonstrated by northern blot and immunoblot with EGFP and TbetaRII probes and antibodies respectively. The membrane localization of this fusion protein was confirmed by confocal microscopy. The functionality of this fusion protein was demonstrated by its blocking effects on TGFbeta action on DNA synthesis and on Y-1 expression of steroidogenic acute regulatory protein (StAR) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD). Moreover, in nude mice the tumorigenicity of cells stably transfected with the fusion protein was higher than that of cells stably transfected with EGFP alone. Taken together, the present results show that TbetaRII-KR/EGFP blocks the effects of TGFbeta1 on Y-1 cells and acts as a potent dominant-negative receptor preventing TGFbeta signaling.