Adaptation Time as a Determinant of the Dosimetric Effectiveness of Online Adaptive Radiotherapy for Bladder Cancer.

Interfraction anatomic deformations decrease the precision of radiotherapy, which can be improved by online adaptive radiation therapy (oART). However, oART takes time, allowing intrafractional deformations. In this study on focal radiotherapy for bladder cancer, we analyzed the time effect of oART on the equivalent uniform dose in the CTV (EUDCTV) per fraction and for the accumulated dose distribution over a treatment series as measure of effectiveness. A time-dependent digital CTV model was built from deformable image registration (DIR) between pre- and post-adaptation imaging. The model was highly dose fraction-specific. Planning target volume (PTV) margins were varied by shrinking the clinical PTV to obtain the margin-specific CTV. The EUDCTV per fraction decreased by-4.4 ± 0.9% of prescribed dose per min in treatment series with a steeper than average time dependency of EUDCTV. The EUDCTV for DIR-based accumulated dose distributions over a treatment series was significantly dependent on adaptation time and PTV margin (p < 0.0001, Chi2 test for each variable). Increasing adaptation times larger than 10 min by five minutes requires a 1.9 ± 0.24 mm additional margin to maintain EUDCTV for a treatment series. Adaptation time is an important determinant of the precision of oART for one half of the bladder cancer patients, and it should be aimed at to be minimized.

Fractionation versus Adaptation for Compensation of Target Volume Changes during Online Adaptive Radiotherapy for Bladder Cancer: Answers from a Prospective Registry.

Online adaptive radiotherapy (ART) allows adaptation of the dose distribution to the anatomy captured by with pre-adaptation imaging. ART is time-consuming, and thus intra-fractional deformations can occur. This prospective registry study analyzed the effects of intra-fraction deformations of clinical target volume (CTV) on the equivalent uniform dose (EUDCTV) of focal bladder cancer radiotherapy. Using margins of 5-10 mm around CTV on pre-adaptation imaging, intra-fraction CTV-deformations found in a second imaging study reduced the 10th percentile of EUDCTV values per fraction from 101.1% to 63.2% of the prescribed dose. Dose accumulation across fractions of a series was determined with deformable-image registration and worst-case dose accumulation that maximizes the correlation of cold spots. A strong fractionation effect was demonstrated-the EUDCTV was above 95% and 92.5% as determined by the two abovementioned accumulation methods, respectively, for all series of dose fractions. A comparison of both methods showed that the fractionation effect caused the EUDCTV of a series to be insensitive to EUDCTV-declines per dose fraction, and this could be explained by the small size and spatial variations of cold spots. Therefore, ART for each dose fraction is unnecessary, and selective ART for fractions with large inter-fractional deformations alone is sufficient for maintaining a high EUDCTV for a radiotherapy series.

Canales dominantes de percepción del conocimiento. Influencia en la evaluación del aprendizaje de la inmunología / Knowledge Perception Dominant Channels. Influence of the Evaluation of Immunology Learning

Introducción: Los estilos de aprendizaje según canales de percepción dominante del conocimiento de los estudiantes influyen en su aprendizaje. Su uso por los docentes puede favorecer o no a estudiantes con un canal específico. Objetivo: Describir la ubicación según los canales de percepción dominante del conocimiento de los estudiantes de medicina y la relación de estos con el resultado de las evaluaciones frecuentes en la asignatura Sangre y Sistema Inmune. Métodos: Se realizó una investigación en 234 estudiantes y 30 profesores de la carrera de medicina en los cursos 2020-2021 y 2022. Los estudiantes se clasificaron según los resultados de un cuestionario para identificar el predominio del canal de percepción (visuales-auditivos-kinestésicos) y a los profesores se les realizó una encuesta para determinar su percepción sobre el uso de estrategias de enseñanza diferenciales para cada canal. El procesamiento se realizó en programa SPSS 25, a través de números, porcentaje y prueba de ji al cuadrado. Resultados: Predominó el canal visual con el 48 por ciento. Existió asociación con el sexo con p = 0,0016; en varones prevaleció el canal auditivo y en hembras el visual. La relación entre los canales de percepción dominante y el rendimiento académico fue significativa con p = 0,000. Conclusiones: Prevaleció el canal de percepción dominante visual. La distribución de cada canal se asoció con el sexo y el rendimiento académico; así se lograron mejores resultados por los estudiantes con percepción dominante visual. Esto último estuvo relacionado con el predominio de acciones por parte de los docentes que potencian este canal de percepción(AU)

Introduction: Learning styles according to dominant perception channels of students' knowledge influence their learning. Their use by professors may or may not favor students with a specific channel. Objective: To describe the location according to the dominant knowledge perception channels of medical students and their relationship with the results of frequent evaluations in the subject Blood and Immune System. Methods: A research was conducted with 234 students and 30 professors of the Medicine major during the academic years 2020-2021 and 2022. The students were classified according to the results of a questionnaire to identify the perception channel predominance (visual-auditory-kinesthetic), while the professors were surveyed to determine their perception on the use of differential teaching strategies for each channel. Processing was performed in SPSS 25, using numbers, percentages and the chi-squared test. Results: The visual channel predominated, accounting for 48 percent. There was an association with sex (p=0.0016); the auditory channel prevailed among males, while the visual channel prevailed among females. The relationship between dominant perception channels and academic performance was significant (p=0.000). Conclusions: The visual dominant perception channel prevailed. The distribution of each channel was associated with sex and academic performance; thus, better results were achieved by students with visual dominant perception. The latter was related to the predominance of actions by professors that enhance this perception channel(AU)

Comparison of Online-Onboard Adaptive Intensity-Modulated Radiation Therapy or Volumetric-Modulated Arc Radiotherapy With Image-Guided Radiotherapy for Patients With Gynecologic Tumors in Dependence on Fractionation and the Planning Target Volume Margin.

Importance: Patients with newly diagnosed locally advanced cervical carcinomas or recurrences after surgery undergoing radiochemotherapy whose tumor is unsuited for a brachytherapy boost need high-dose percutaneous radiotherapy with small margins to compensate for clinical target volume deformations and set-up errors. Cone-beam computed tomography-based online adaptive radiotherapy (ART) has the potential to reduce planning target volume (PTV) margins below 5 mm for these tumors. Objective: To compare online ART technologies with image-guided radiotherapy (IGRT) for gynecologic tumors. Design, Setting, and Participants: This comparative effectiveness study comprised all 7 consecutive patients with gynecologic tumors who were treated with ART with artificial intelligence segmentation from January to May 2022 at the West German Cancer Center. All adapted treatment plans were reviewed for the new scenario of organs at risk and target volume. Dose distributions of adapted and scheduled plans optimized on the initial planning computed tomography scan were compared. Exposure: Online ART for gynecologic tumors. Main Outcomes and Measures: Target dose coverage with ART compared with IGRT for PTV margins of 5 mm or less in terms of the generalized equivalent uniform dose (gEUD) without increasing the gEUD for the organs at risk (bladder and rectum). Results: The first 10 treatment series among 7 patients (mean [SD] age, 65.7 [16.5] years) with gynecologic tumors from a prospective observational trial performed with ART were compared with IGRT. For a clinical PTV margin of 5 mm, IGRT was associated with a median gEUD decrease in the interfractional clinical target volume of -1.5% (90% CI, -31.8% to 2.9%) for all fractions in comparison with the planned dose distribution. Online ART was associated with a decrease of -0.02% (90% CI, -3.2% to 1.5%), which was less than the decrease with IGRT (P < .001). This was not associated with an increase in the gEUD for the bladder or rectum. For a PTV margin of 0 mm, the median gEUD deviation with IGRT was -13.1% (90% CI, -47.9% to 1.6%) compared with 0.1% (90% CI, -2.3% to 6.6%) with ART (P < .001). The benefit associated with ART was larger for a PTV margin of 0 mm than of 5 mm (P = .004) due to spreading of the cold spot at the clinical target volume margin from fraction to fraction with a median SD of 2.4 cm (90% CI, 1.9-3.4 cm) for all patients. Conclusions and Relevance: This study suggests that ART is associated with an improvement in the percentage deviation of gEUD for the interfractional clinical target volume compared with IGRT. As the gain of ART depends on fractionation and PTV margin, a strategy is proposed here to switch from IGRT to ART, if the delivered gEUD distribution becomes unfavorable in comparison with the expected distribution during the course of treatment.

Emergence of Fosfomycin Resistance by Plasmid-Mediated fos Genes in Uropathogenic ESBL-Producing E. coli Isolates in Mexico.

Fosfomycin is currently a viable option against urinary tract infections, particularly against extended-spectrum ß-lactamases (ESBL)-producing E. coli, due to its unique mechanism of action and its low resistance among bacteria. The objective of this study was to investigate two of the three most common mechanisms of resistance against this antibiotic among 350 ESBL-producing E. coli strains isolated from the urine of Mexican patients. The prevalence of fosfomycin resistance in our study was 10.9% (38/350). Of all resistant isolates analyzed, 23 (60.5%) were identified as fos-producing organisms, with 14 strains carrying fosA3 and 9, fosA1. Additionally, 11 (28.9%) fosfomycin-resistant isolates presented resistance due to impaired antibiotic transport and 8 (21.0%) both mechanisms. No resistance mechanism investigated in the study was found on 12 strains. All 38 confirmed ESBL-producing isolates carried a blaCTX-M subtype, 36 (94.5%) belonged to the O25b-ST131 clone, and all of them were able to transfer the fosfomycin resistance trait to recipient strains horizontally. This is the first study in Mexico demonstrating a plasmid-mediated fosfomycin resistance mechanism among clinical E. coli strains. Since our results suggest a strong association among fos and blaCTX-M genes and ST131 clones in uropathogenic E. coli, plasmid-mediated fosfomycin resistance should be closely monitored.

Prediction of malignant lymph nodes in NSCLC by machine-learning classifiers using EBUS-TBNA and PET/CT.

Accurate determination of lymph-node (LN) metastases is a prerequisite for high precision radiotherapy. The primary aim is to characterise the performance of PET/CT-based machine-learning classifiers to predict LN-involvement by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in stage-III NSCLC. Prediction models for LN-positivity based on [18F]FDG-PET/CT features were built using logistic regression and machine-learning models random forest (RF) and multilayer perceptron neural network (MLP) for stage-III NSCLC before radiochemotherapy. A total of 675 LN-stations were sampled in 180 patients. The logistic and RF models identified SUVmax, the short-axis LN-diameter and the echelon of the considered LN among the most important parameters for EBUS-positivity. Adjusting the sensitivity of machine-learning classifiers to that of the expert-rater of 94.5%, MLP (P = 0.0061) and RF models (P = 0.038) showed lower misclassification rates (MCR) than the standard-report, weighting false positives and false negatives equally. Increasing the sensitivity of classifiers from 94.5 to 99.3% resulted in increase of MCR from 13.3/14.5 to 29.8/34.2% for MLP/RF, respectively. PET/CT-based machine-learning classifiers can achieve a high sensitivity (94.5%) to detect EBUS-positive LNs at a low misclassification rate. As the specificity decreases rapidly above that level, a combined test of a PET/CT-based MLP/RF classifier and EBUS-TBNA is recommended for radiation target volume definition.

Diferentes formas de presentación de la anemia megaloblástica en el lactante / Different forms of presentation of megaloblastic anemia in the infant

Introducción: La anemia megalobástica es un trastorno madurativo de los precursores eritroides y mieloides causado por déficit de vitamina B12, ácido fólico, o ambos. Es poco común en la infancia y su prevalencia se desconoce por ser una enfermedad poco frecuente. Objetivo: Describir diferentes formas de presentación de la anemia megaloblástica en el lactante. Presentación de casos: Se presentan dos casos de lactantes, en el caso 1 la madre tuvo una alimentación precaria durante el embarazo y la lactancia, prolongó la lactancia materna exclusiva más de 6 meses. La paciente comenzó a perder las habilidades ganadas en el desarrollo psicomotor y presentó trastornos neurológicos graves, por lo que se consideró que se trataba de una enfermedad progresiva del sistema nervioso central. En el caso 2, en el que se prolongó la lactancia materna exclusiva, apareció trombocitopenia, por lo que se sospechó una enfermedad hematológica maligna. Resultados: En ambos casos después de realizar diversas pruebas para descartar enfermedades neurológicas (caso 1) y enfermedades hematológicas (caso 2) se diagnosticó anemia megaloblástica por déficit de vitamina B12 por disminución en la ingesta y una reserva limítrofe en la madre que lacta. En ambos casos los síntomas desaparecieron con el tratamiento vitamínico sustitutivo. Conclusiones: En el lactante la anemia megaloblástica se puede presentar de diferentes formas clínicas a pesar de tener la misma causa, un déficit en la ingesta y una reserva escasa de la madre durante el embarazo y lactancia(AU)

Introduction: Megaloblastic anemia is a maturing disorder of the erythroid and myeloid precursors caused by deficiency of vitamin B12, folic acid, or both. It is uncommon in childhood and its prevalence is unknown because it is a rare disease. Objective: To describe different forms of presentation of megaloblastic anemia in infants. Presentation of cases: Two cases of infants are presented, in case 1 the mother had a precarious diet during pregnancy and lactation, and prolonged exclusive breastfeeding more than 6 months. The patient began to lose the skills gained in psychomotor development and presented severe neurological disorders, so it was considered that it was a progressive disease of the central nervous system. In case 2, in which exclusive breastfeeding was prolonged, thrombocytopenia appeared, so a malignant hematological disease was suspected. Results: In both cases, after performing various tests to rule out neurological diseases (case 1) and hematological diseases (case 2), megaloblastic anemia was diagnosed due to vitamin B12 deficiency due to a decrease in intake and a borderline reserve in the breastfeeding mother. In both cases the symptoms disappeared with vitamin replacement therapy. Conclusions: In the infant, megaloblastic anemia can occur in different clinical ways despite having the same cause, a deficit in intake and a low reserve of the mother during pregnancy and lactation(AU)

Correspondencia vacunación-inmunización como necesidad social y reto para la ciencia y la educación médica / Vaccination-immunization correspondence as a social need and challenge for science and medical education

Introducción: La vacunación constituye el arma preventiva más efectiva para las enfermedades trasmisibles que conoce la humanidad. Hacer que las vacunas aplicadas sean realmente inmunizantes resulta la responsabilidad de los profesionales de la atención primaria. Del mismo modo, es importante que se acepte, sin recelo, la vacunación, sobre todo en la situación epidemiológica actual. Objetivo: Describir las implicaciones sociales, económicas y éticas relacionadas con la existencia de vacunas teóricamente no inmunizantes. Métodos: Se emplearon los resultados de un programa de intervención educativa en edades pediátricas en el Policlínico 13 de marzo. Se utilizó la prueba de rangos con signo de Wilcoxon, con índice de confianza del 95 por ciento. Resultados: Inicialmente, predominó el nivel inadecuado de conocimiento, que luego mejoró significativamente. Se recuperaron 48 niños no vacunados y 29 vacunaciones no inmunizados. Conclusiones: No existe correspondencia entre las coberturas vacunales y la inmunización. Están instauradas, como correctas, falsas contraindicaciones para la vacunación. La intervención educativa fue efectiva, y se hizo patente la pertinencia de programas de pregrado y posgrado que perfeccionen la formación de los profesionales y la calidad en el desempeño profesional(AU)

Introduction: Vaccination is the most effective preventive weapon for communicable diseases known to humanity. It is the responsibility of primary health care professionals to ensure that the administered vaccines are truly immunizing. Likewise, it is important that vaccination be accepted without hesitations, especially in the current epidemiological situation. Objective: To describe the social, economic and ethical implications related to the existence of theoretically nonimmunizing vaccines. Methods: The results of an educational intervention program in pediatric ages at 13 de Marzo Policlinic were used. The Wilcoxon signed-rank test was used, with a confidence index of 95 percent. Results: Initially, an inadequate level of knowledge predominated, which later improved significantly. Forty-eight unvaccinated children and 29 unimmunized children recovered. Conclusions: There is no correspondence between vaccination coverage and immunization. False contraindications for vaccination are established as correct. The educational intervention was effective, while the relevance became evident for undergraduate and postgraduate programs to improve the training of professionals and the quality of professional performance(AU)

Síndrome de úlceras en piernas de carácter familiar y comienzo precoz / Familial Leg Ulcer Syndrome of Early Onset

Introducción: Las úlceras en las piernas son llagas sin sanar o lesiones abiertas de etiología multifactorial. Constituyen una patología importante en la práctica diaria de los profesionales de la salud en todos los niveles de asistencia. Objetivo: Presentar un caso infrecuente con una afección genética hereditaria familiar que provocó lesiones ulcerosas en las extremidades inferiores. Presentación del caso: Paciente masculino de 30 años con lesiones ulcerosas en ambos miembros inferiores, de 18 años de años de evolución, muy dolorosas con signos de infección local severa. Presentó diagnóstico de úlceras inespecíficas en ambos miembros inferiores. Fue ingresado con toma de su estado general, gran limitación de la deambulación, dolor intenso en ambas piernas, lesiones abundantes ulcerosas sucias diseminadas en ambas piernas, de fondo amarillento, con secreción amarilla clara, muy fétida. Se realizó estudio clínico, humoral, imagenológico, microbiológico y anátomo-histopatológico. Conclusiones: Se diagnostica síndrome de úlceras en piernas de carácter familiar y comienzo precoz, de herencia recesiva ligada al cromosoma X. Se requieren estudios a mayor escala para evaluar las contribuciones de los factores genéticos en la génesis de esta enfermedad, los cuales podrían ser la clave para comprender mejor su desarrollo(AU)

Introduction: Leg ulcers are unhealed sores or open lesions of multifactorial etiology. They constitute an important pathology in the daily practice of health professionals at all levels of care. Objective: To report an infrequent case with a familial hereditary genetic condition that caused ulcerative lesions in the lower limbs. Case report: We report the case of a 30-year-old male patient with ulcerative lesions on both lower limbs, 18 years of evolution, very painful with signs of severe local infection. He had diagnosis of nonspecific ulcers in both lower limbs. He was admitted with poor general condition, great limitation of ambulation, intense pain in both legs, abundant dirty yellowish ulcerative lesions scattered on both legs, and light yellow, very foul-smelling discharge. A clinical, humoral, imaging, microbiological and anatomical-histopathological study was performed. Conclusions: The diagnosis was familial leg ulcer syndrome of early onset, recessive inheritance linked to the X chromosome, is diagnosed. Larger scale studies are required to assess the contributions of genetic factors in the genesis of this disease, which could be the key to better understand its development(AU)

Atención integral a escolares con trastorno por déficit de atención con hiperactividad: estudio de caso / Comprehensive care for schoolchildren with attention deficit hyperactivity disorder: a case study

RESUMEN Fundamento: la labor conjunta del sector educacional y de la salud en Cuba encamina sus esfuerzos hacia la prevención, y establece vínculos para mejorar la calidad de vida de las personas que padecen del trastorno por déficit de atención con hiperactividad. Objetivo: describir resultados parciales de una investigación realizada en el municipio Santa Clara, provincia Villa Clara, basada en la atención integral a escolares con trastorno por déficit de atención con hiperactividad, mediante la articulación de la educación primaria con instituciones de salud mental. Métodos: el estudio fue realizado con un enfoque cualitativo a partir del diseño de una investigación-acción y se utilizó el estudio de caso como estrategia de investigación en el periodo 2014-2019 en cuatro instituciones de la educación primaria y las respectivas áreas de salud mental. Se emplearon métodos del nivel teórico y empírico, y entre las técnicas, el diario del investigador y el análisis de evidencias. Resultados: los obstáculos y progresos del propio proceso investigativo permitieron la concepción de la atención integral a escolares con trastorno por déficit de atención con hiperactividad, y la materialización de su efectividad en la evolución de los escolares, la preparación de familias y docentes, y el intercambio entre las instituciones educativas y de salud. Conclusiones: la concepción de la atención integral a escolares con trastorno por déficit de atención con hiperactividad con una perspectiva multisectorial desde los sectores educativos y sanitarios involucra a docentes y especialistas de salud en una atención individualizada para reducir las consecuencias del trastorno.

ABSTRACT Background: the joint work of the educational and health sector in Cuba directs its efforts towards prevention, and establishes links to improve the quality of life of people suffering from attention deficit hyperactivity disorder. Objective: to describe partial results of a research carried out in the Santa Clara municipality, Villa Clara province, based on comprehensive care for schoolchildren with attention deficit hyperactivity disorder, through the articulation of primary education with mental health institutions. Methods: the study was carried out with a qualitative approach based on the design of an action research and the case study was used as a research strategy in the period from 2014 to 2019 in four primary education institutions and the respective areas of mental health. Methods of the theoretical and empirical level were used, and among the techniques, the researcher's diary and the analysis of evidence. Results: the obstacles and progress of the research process itself allowed the conception of comprehensive care for schoolchildren with attention deficit hyperactivity disorder, and the materialization of its effectiveness in the evolution of schoolchildren, the preparation of families and teachers, and the exchange between educational and health institutions. Conclusions: the conception of comprehensive care for schoolchildren with attention deficit hyperactivity disorder with a multisectoral perspective from the educational and health sectors involves teachers and health specialists in individualized care to reduce the consequences of the disorder.

Frequency and expression of genes involved in adhesion and biofilm formation in Staphylococcus aureus strains isolated from periodontal lesions.

BACKGROUND/PURPOSE: The aim of this study was to characterize the Staphylococcus aureus strains isolated from periodontal lesions of patients, to determine the expression of genes involved in cell adhesion upon their infection of human epithelial cells using an in vitro model, its biofilm formation, and its resistance to antibiotics. METHODS: S. aureus was analysed by PCR, Kirby-Bauer, and pulsed-field gel electrophoresis (PFGE), measuring gene expression by real-time PCR after infection of human cells in vitro. RESULTS: S. aureus was identified in 18.6% (50/268) of the samples. All strains (n = 50) possessed the virulence genes spa (Staphylococcal protein A), coa (coagulase), and icaAB (intercellular adhesin); 96% (n = 48) possessed clfB (clumping factor B), and 88% (n = 44) possessed ebps (elastin-binding protein) and sdrD (serine aspartate repeat protein D). All strains were resistant to methicillin, ampicillin, dicloxacillin, cefotaxime, and penicillin, and were multidrug resistant to 6-12 antibiotics. PFGE analysis showed 37 different pulsed-field types and most strains (60.4%) had a unique pulsed-field type. Twenty-four distinct combinations of virulence genes and antibiotic-resistant phenotypes were identified. CONCLUSION: Although S. aureus has been considered a transient member of the oral microbiota, our results indicate a high-level expression of virulence genes and multidrug resistance in the strains isolated from periodontal lesions. These strains might complicate the successful treatment of the disease.

Estudios de agregación plaquetaria como endofenotipo de las alteraciones hereditarias de la fibra colágena / Platelet aggregation studies as an endophenotype of hereditary disorders of collagen fiber

Introducción: Las plaquetas contribuyen a la hemostasia y la interrupción heredada o adquirida; en sus procesos bioquímicos pueden alterar la función plaquetaria. Estos trastornos de agregación se han asociado a enfermedades genéticas con afectación del tejido conectivo como el síndrome Ehlers-Danlos, cuyo diagnóstico diferencial con el espectro de hipermovilidad articular resulta difícil clínica y molecularmente. Estas entidades con afectación en las fibras colágenas y diferente repercusión clínica precisan diferenciales en su diagnóstico clínico. Métodos: Se revisaron 353 historias clínicas de pacientes atendidos en el Servicio de Genética del Hospital Pediátrico William Soler desde septiembre del 2009 al 2012, con diagnóstico de hipermovilidad articular por criterios de Beighton y de Ehlers-Danlos según Villefranche (1997). Se incluyó a los pacientes de 5-18 años con resultados documentados del estudio de agregación plaquetaria, valorados por especialistas en hematología. Resultados: Se encontraron trastornos de agregación plaquetaria en 79 de 86 pacientes (92 por ciento). En 7 casos con hipermovilidad de 65 con este diagnóstico (10 por ciento), los resultados fueron negativos. Los 21 con síndrome Ehlers-Danlos tuvieron afectaciones con los fosfolípidos plaquetarios. La hipermovilidad articular estuvo asociada a la combinación difosfato de adenosina (ADP)-epinefrina y el Ehlers-Danlos a la combinación ADP-epinefrina-colágeno-fosfolípidos. Conclusiones: Los pacientes con hipermovilidad articular mostraron asociación a defectos de liberación de gránulos con agonistas como el ADP-epinefrina y los Ehlers-Danlos con la disponibilidad de los fosfolípidos, relacionados con el cambio de forma plaquetaria. Este resultado puede ser una herramienta para conocer el endofenotipo funcional plaquetario como elemento diferencial en los trastornos de la fibra colágena(AU)

Introduction: Platelets contribute to hemostasis and inherited or acquired interruption; in its biochemical processes it can alter platelet function. These aggregation disorders have been associated with genetic diseases with connective tissue involvement such as Ehlers-Danlos syndrome, whose differential diagnosis with the spectrum of joint hypermobility is clinically and molecularly difficult. These entities with involvement of the collagen fibers and different clinical repercussions require differentials in their clinical diagnosis. Methods: 353 medical records of patients attended in the Genetics service of the William Soler Pediatric Hospital from September 2009 to 2012, with a diagnosis of joint hypermobility by Beighton and Ehlers-Danlos criteria according to Villefranche (1997) were reviewed. Patients aged 5-18 years were included with documented results of the platelet aggregation study, assessed by specialists in hematology. Results: Platelet aggregation disorders were found in 79 of 86 patients (92 percent). In 7 cases with hypermobility of 65 with this diagnosis (10 percent), the results were negative. The 21 with Ehlers-Danlos syndrome had affectations with platelet phospholipids. Joint hypermobility was associated with the combination adenosine diphosphate (ADP) -epinephrine and the Ehlers-Danlos with the combination ADP-epinephrine-collagen-phospholipids. Conclusions: Patients with joint hypermobility showed an association to granule release defects with agonists such as ADP-epinephrine and Ehlers-Danlos with the availability of phospholipids, related to platelet shape change. This result can be a tool to know the platelet functional endophenotype as a differential element in collagen fiber disorders(AU)

Diagnóstico de aciduria metilmalónica en el periodo 2013-2018 / Diagnosis of Methyl Malonicaciduria from 2013 to 2018

RESUMEN Fundamento: la aciduria metilmalónica es una de las acidurias orgánicas más frecuentes y agrupa un conjunto de defectos genéticos caracterizados por la excreción de niveles elevados de ácido metilmalónico en la orina. La excreción de este metabolito puede ir acompañada o no de niveles elevados de homocisteína en dependencia de la ruta metabólica afectada. Objetivo describir la implementación de una metodología de laboratorio que combina el ácido metilmalónico y la homocisteína en el diagnóstico diferencial y seguimiento de la aciduria metilmalónica en el periodo de 2013 a 2018. Métodos: a los pacientes con incremento de ácido metilmalónico en el perfil de ácidos orgánicos, se les cuantificó homocisteína en plasma y orina. La identificación del ácido metilmalónico se realizó por cromatografía gaseosa/ espectrometría de masas, mientras que la cuantificación de homocisteína por cromatografía líquida de alta resolución. Resultados: los métodos cromatográficos permitieron la identificación y cuantificación del ácido metilmalónico y la homocisteína, respectivamente. La homocisteína se cuantificó en siete pacientes con niveles incrementados de aciduria metilmalónica. Los niveles de homocisteína en cuatro de ellos fueron superiores a los valores normales, sugiriendo una aciduria combinada con homocistinuria. Tres de los pacientes con aciduria metilmalónica combinada bajo tratamiento mostraron una disminución en los niveles de ambos metabolitos, correspondiendo con una satisfactoria evolución. Conclusiones: la metodología implementada con los análisis de la determinación simultánea de ambos marcadores permitió el diagnóstico diferencial y seguimiento bioquímico de la aciduria metilmalónica.

ABSTRACT Foundation: methylmalonic aciduria is one of the most frequent organic acidurias and groups together a set of genetic defects, characterized by the excretion of elevated levels of urinemethyl malonic acid. The excretion of this metabolite may or may not be accompanied by elevated homocysteine ​​levels depending on the affected metabolic pathway. Objective: to describe the implementation of a laboratory methodology that combines methylmalonic acid and homocysteine ​​in the differential diagnosis and monitoring of methylmalonic aciduria in the period from 2013 to 2018. Methods: for patients with an increase in methylmalonic acid in the organic acid profile, homocysteine ​​was quantified in plasma and urine. The identification of methylmalonic acid was performed by gas chromatography / mass spectrometry, while the homocysteine ​​quantification by high performance liquid chromatography. Results: chromatographic methods allowed the identification and quantification of methylmalonic acid and homocysteine, respectively. Homocysteine ​​was quantified in seven patients with increased levels of methylmalonic aciduria. Homocysteine ​​levels in four of them were higher than normal values, suggesting aciduria combined with homocystinuria. Three of the patients with combined methylmalonic aciduria under treatment showed a decrease in the levels of both metabolites, corresponding to a satisfactory evolution. Conclusions: simultaneous determination of both markers allowed differential diagnosis and biochemical monitoring of this disease.

The Evolution of Antimicrobial Resistance in Mexico During the Last Decade: Results from the INVIFAR Group.

Background: Surveillance of antimicrobial resistance (AMR) requires an international approach with national and local strategies. Our aim was to summarize a retrospective 10-year report of antibiotic resistance of gram-positive and gram-negative bacteria in Mexico. Methods: A total of 46 centers from 22 states of Mexico participated. Databases of AMR from January 2009 to December 2018 were included for most species. The 10-year period was divided into five 2-year periods. Results: For Staphylococcus aureus, a decrease in resistance in all specimens was observed for erythromycin and oxacillin (p < 0.0001 for each). For Enterobacter spp., resistance to meropenem increased for urine specimens (p = 0.0042). For Klebsiella spp., increased drug resistance in specimens collected from blood was observed for trimethoprim/sulfamethoxazole, gentamicin, tobramycin (p < 0.0001 for each), meropenem (p = 0.0014), and aztreonam (p = 0.0030). For Acinetobacter baumannii complex, high drug resistance was detected for almost all antibiotics, including carbapenems, except for tobramycin, which showed decreased resistance for urine, respiratory, and blood isolates (p < 0.0001 for each), and for amikacin, which showed a decrease in resistance in urine specimens (p = 0.0002). An increase in resistance to cefepime was found for urine, respiratory, and blood specimens (p < 0.0001 for each). For Pseudomonas aeruginosa, aztreonam resistance increased for isolates recovered from blood (p = 0.0001). Conclusion: This laboratory-based surveillance of antibiotic resistance shows that resistance is increasing for some antibiotics in different bacterial species in Mexico and highlights the need for continuous monitoring of antibiotic resistance.

Algoritmo para el diagnóstico de pacientes con trastornos del neurodesarrollo y sospecha de un síndrome genético / Algorithm for the diagnosis of patients with neurodevelopmental disorders and suspicion of a genetic syndrome

El amplio espectro de aberraciones cromosómicas observable en los trastornos del neurodesarrollo no siempre puede ser caracterizado por análisis cromosómico. El objetivo del trabajo fue determinar la etiología genética de estos trastornos en pacientes con afecciones neurológicas congénitas y sospecha clínica de un síndrome genético, aplicando un algoritmo de estudio clínico-molecular. En 71 de 111 niños analizados, se hallaron aberraciones submicroscópicas asociadas a síndromes de microdeleción-microduplicación: DiGeorge (22 casos), Prader-Willi (26 casos), Angelman (2 casos), Williams-Beuren (17 casos), Smith-Magenis (1 caso), Miller-Dieker (1 caso) y síndrome cri du chat (1 caso). Adicionalmente, se detectó una inserción desbalanceada de novo de la región 17p12p11.2, en el punto 5p13.1, en un niño de tres años. La utilización del método clínico unido a técnicas moleculares, como hibridación fluorescente in situ, ha permitido, en la mayoría de los casos, el diagnóstico certero de pacientes y/o familias con trastornos del neurodesarrollo.

The wide range of chromosome aberrations seen in neurodevelopmental disorders may not always be characterized by means of a chromosome analysis. The objective of this study was to determine the genetic etiology of these disorders in patients with congenital neurological conditions and clinical suspicion of a genetic disorder using a clinical and molecular testing algorithm. Among 111 studied children, 71 showed submicroscopic chromosome aberrations associated with microdeletion/microduplication syndromes: DiGeorge (22 cases), Prader-Willi (26 cases), Angelman (2 cases), Williams-Beuren (17 cases), Smith-Magenis (1 case), Miller-Dieker (1 case), and cri du chat syndrome (1 case). Additionally, a de novo trisomy 17p12p11.2 due to an unbalanced insertion into 5p13.1 was identified in a 3-year-old child. In most cases, the use of a clinical method together with molecular techniques, such as fluorescence in situ hybridization, has allowed to make an accurate diagnosis in patients and/or families with neurodevelopmental disorders.

Algorithm for the diagnosis of patients with neurodevelopmental disorders and suspicion of a genetic syndrome. / Algoritmo para el diagnóstico de pacientes con trastornos del neurodesarrollo y sospecha de un síndrome genético.

The wide range of chromosome aberrations seen in neurodevelopmental disorders may not always be characterized by means of a chromosome analysis. The objective of this study was to determine the genetic etiology of these disorders in patients with congenital neurological conditions and clinical suspicion of a genetic disorder using a clinical and molecular testing algorithm. Among 111 studied children, 71 showed submicroscopic chromosome aberrations associated with microdeletion/microduplication syndromes: DiGeorge (22 cases), Prader-Willi (26 cases), Angelman (2 cases), WilliamsBeuren (17 cases), Smith-Magenis (1 case), Miller-Dieker (1 case), and cri du chat syndrome (1 case). Additionally, a de novo trisomy 17p12p11.2 due to an unbalanced insertion into 5p13.1 was identified in a 3-year-old child. In most cases, the use of a clinical method together with molecular techniques, such as fluorescence in situ hybridization, has allowed to make an accurate diagnosis in patients and/or families with neurodevelopmental disorders.

El amplio espectro de aberraciones cromosómicas observable en los trastornos del neurodesarrollo no siempre puede ser caracterizado por análisis cromosómico. El objetivo del trabajo fue determinar la etiología genética de estos trastornos en pacientes con afecciones neurológicas congénitas y sospecha clínica de un síndrome genético, aplicando un algoritmo de estudio clínico-molecular. En 71 de 111 niños analizados, se hallaron aberraciones submicroscópicas asociadas a síndromes de microdeleción-microduplicación: DiGeorge (22 casos), Prader-Willi (26 casos), Angelman (2 casos), Williams-Beuren (17 casos), Smith-Magenis (1 caso), Miller-Dieker (1 caso) y síndrome cri du chat (1 caso). Adicionalmente, se detectó una inserción desbalanceada de novo de la región 17p12p11.2, en el punto 5p13.1, en un niño de tres años. La utilización del método clínico unido a técnicas moleculares, como hibridación fluorescente in situ, ha permitido, en la mayoría de los casos, el diagnóstico certero de pacientes y/o familias con trastornos del neurodesarrollo.

Factores de riesgo que influyen en el abandono de la Lactancia Materna.2017-2018 / Risk factors that influence the abandonment of Breastfeeding. 2017 - 2018

Introducción: la leche materna contiene todos los nutrientes necesarios para el desarrollodel niño y tiene varias ventajas sobre cualquier sustituto desarrollado. Es considerada la vacuna más perfecta de todos los tiempos; debido al incremento del abandono de la lactancia materna exclusiva antes de los seis meses de vida se hace necesario identificar los factores de riesgo que influyen en esto. Objetivo: identificar los factores de riesgo bio-sociales que influyen en el abandono de la lactancia materna exclusiva antes del sexto mes de vida en el Policlínico 13 de Marzo, Bayamo, Granma; en el período de enero a diciembre del 2018. Método: se realizó un estudio descriptivo retrospectivo de caso y control, con el propósito de identificar los factores de riesgo que influyen en el abandono de la lactancia exclusiva antes del sexto mes de vida. En el grupo caso se incluyeron las que abandonaron la lactancia maternay en el grupo control las queofrecieron lactancia exclusiva a su hijo hasta el 6to mes de vida; se les pidió un consentimiento informado y se aplicó un cuestionario a las madres objetos de estudio.Resultados: se estudiaron 147madres, en el grupo caso el abandono la lactancia fue más frecuente en menores de 20 años, con nivel secundario o preuniversitario, con familias disfuncionales en el 73,5 por ciento y según lo referido por tener la sensación de que el bebé pasa hambre, no se llena o no tienensuficiente leche en el pecho. Conclusiones: la edad materna inferior de 20 años, el bajo nivel de escolaridad, la familia disfuncional y la desacertada percepción de que élbebé pasa hambre o no se llena por no tener suficiente leche en el pecho, son los principales factores que provocan el abandono de la lactancia en nuestra investigación causando la introducción de otros tipos de leche disponibles(AU)

Introduction: breast milk contains all the nutrients necessary for the development of the child and has several advantages over any developed substitute. It is considered the most perfect vaccine of all time; due to the increase in the abandonment of exclusive breastfeeding before six months of life it is necessary to identify the risk factors that influence this. Objective:to identify the bio-social risk factors that influence the abandonment of exclusive breastfeeding before the sixth month of life in the Polyclinic March 13, Bayamo, Granma; in the period from January to December 2018. Method: a retrospective case-control and descriptive study was carried out, with the purpose of identifying the risk factors that influence the abandonment of exclusive breastfeeding before the sixth month of life. In the case group were included those who abandoned breastfeeding and in the control group those who offered exclusive breastfeeding to their child until the 6th month of life; Informed consent was requested and a questionnaire was applied to the mothers under study. Results: 147 mothers were studied, in the case group, breastfeeding abandonment was more frequent in children under 20 years of age, with secondary or pre-university level, with dysfunctionalfamilies in 73.5 percent and as referred to as having the feeling that the Baby goes hungry, does not get full or do not have enough breast milk. Conclusions: the maternal age under 20 years of age, the low level of schooling, the dysfunctional family and the misguided perception that the baby is hungry or not full due to not having enough breast milk, are the main factors that cause abandonment of breastfeeding in our research causing the introduction of other types of milk available(EU)

Factores de riesgo que influyen en el abandono de la Lactancia Materna. 2017-2018 / Risk factors that influence the abandonment of Breastfeeding. 2017-2018 / Fatores de risco que influenciam o abandono da amamentação. 2017-2018

RESUMEN Introducción: la leche materna contiene todos los nutrientes necesarios para el desarrollo del niño y tiene varias ventajas sobre cualquier sustituto desarrollado. Es considerada la vacuna más perfecta de todos los tiempos; debido al incremento del abandono de la lactancia materna exclusiva antes de los seis meses de vida se hace necesario identificar los factores de riesgo que influyen en esto. Objetivo: identificar los factores de riesgo bio-sociales que influyen en el abandono de la lactancia materna exclusiva antes del sexto mes de vida en el Policlínico13 de Marzo, Bayamo, Granma; en el período de enero a diciembre del 2018. Método: se realizó un estudio descriptivo retrospectivo de caso y control, con el propósito de identificar los factores de riesgo que influyen en el abandono de la lactancia exclusiva antes del sexto mes de vida. En el grupo caso se incluyeron las que abandonaron la lactancia materna y en el grupo control las que ofrecieron lactancia exclusiva a su hijo hasta el 6to mes de vida; se les pidió un consentimiento informado y se aplicó un cuestionario a las madres objetos de estudio. Resultados: se estudiaron 147 madres, en elgrupo caso el abandono la lactancia fue más frecuente en menores de 20 años, con nivel secundario o preuniversitario, con familias disfuncionales en el 73,5% y según lo referido por tener la sensación de que el bebé pasa hambre, no se llena o no tienen suficiente leche en el pecho. Conclusiones: la edad materna inferior de 20 años, el bajo nivel de escolaridad, la familia disfuncional y la desacertada percepción de que él bebé pasa hambre o no se llena por no tener suficiente leche en el pecho, son los principales factores que provocan el abandono de la lactancia en nuestra investigación causando la introducción de otros tipos de leche disponibles.

ABSTRACT Introduction: breast milk contains all the nutrients necessary for the development of the child and has several advantages over any developed substitute. It is considered the most perfect vaccine of all time; Due to the increase in the abandonment of exclusive breastfeeding before six months of life it is necessary to identify the risk factors that influence this. Objective: to identify the bio-social risk factors that influence the abandonment of exclusive breastfeeding before the sixth month of life in the Polyclinic March 13, Bayamo, Granma; in the period from January to December 2018. Method: a retrospective case-control and descriptive study was carried out, with the purpose of identifying the risk factors that influence the abandonment of exclusive breastfeeding before the sixth month of life. In the case group were included those who abandoned breastfeeding and in the control group those who offered exclusive breastfeeding to their child until the 6th month of life; Informed consent was requested and a questionnaire was applied to the mothers under study. Results: 147 mothers were studied, in the case group, breastfeeding abandonment was more frequent in children under 20 years of age, with secondary or pre-university level, with dysfunctional families in 73.5% and as referred to as having the feeling that the Baby goes hungry, does not get full or do not have enough breast milk. Conclusions: the maternal age under 20 years of age, the low level of schooling, the dysfunctional family and the misguided perception that the baby is hungry or not full due to not having enough breast milk, are the main factors that cause abandonment of breastfeeding in our research causing the introduction of other types of milk available.

RESUMO Introdução: o leite materno contém todos os nutrientes necessários para o desenvolvimento da criança e possui várias vantagens sobre qualquer substituto desenvolvido. É considerada a vacina mais perfeita de todos os tempos; Devido ao aumento do abandono do aleitamento materno exclusivo antes dos seis meses de vida, é necessário identificar os fatores de risco que influenciam isso. Objetivo: identificar os fatores de risco biossociais que influenciam o abandono do aleitamento materno exclusivo antes do sexto mês de vida na Policlínica em 13 de março, Bayamo, Granma; no período de janeiro a dezembro de 2018. Método: foi realizado um estudo descritivo retrospectivo de caso e controle, com o objetivo de identificar os fatores de risco que influenciam o abandono do aleitamento materno exclusivo antes do sexto mês de vida. No grupo caso foram incluídos aqueles que abandonaram a amamentação e no grupo controle aqueles que ofereceram aleitamento materno exclusivo ao filho até o sexto mês de vida; Foi solicitado o consentimento informado e aplicado um questionário às mães estudadas. Resultados: foram estudadas 147 mães, no grupo caso, o abandono do aleitamento materno foi mais frequente em menores de 20 anos, com nível secundário ou pré-universitário, com famílias disfuncionais em 73,5% e referido como tendo a sensação de que o O bebê passa fome, não fica cheio ou não tem leite materno suficiente. Conclusões: idade materna abaixo de 20 anos, baixa escolaridade, família disfuncional e a infeliz percepção de que o bebê está com fome ou não está cheio por não ter leite suficiente, são os principais fatores que causam o abandono amamentação em nossa pesquisa, causando a introdução de outros tipos de leite disponíveis.

O-serogroups of multi-drug resistant cervicovaginal Escherichia coli harboring a battery of virulence genes.

Multi-drug resistant cervicovaginal Escherichia coli (CVEC) infections are a serious health problem. The aim of this study is to determine the patterns of virulence genes, antibiotic resistance and O-serogroups of CVEC isolated in Mexico. Two hundred strains of CVEC were isolated from women attending two Clinics at the Instituto Mexicano del Seguro Social. E. coli O-serogroups and virulence markers were identified by PCR. Antibiotic susceptibility was determined using the Kirby-Bauer disc-diffusion method. Serogroups O25 (50%), O75 (9%) and O15 (7.5%) were the most frequent among the CVEC strains isolated. The frequencies for antibiotic resistance were ampicillin 97%, (n = 194); carbenicillin 93.5%, (n = 187); cefalotin 77%, (n = 154); and nitrofurantoin 71%, (n = 142). The frequency of multiresistant isolates (3-12 drugs) was 197 (98.5%). The most frequent virulence genes found were feoB (91.5%), fimH (89.5%), kpsMT11 (75%), iutA (66%), and iroN (59%). One hundred and four distinct patterns of virulence markers with antibiotic-resistance genes associated with O-serogroups were identified amongst CVEC isolates. In conclusion: most CVEC strains isolated were multiresistant to antibiotics, belonged to three O-serogroups, and possessed a battery of virulence factors. This knowledge may lead to improved guidelines and standards for treating cervicovaginal infections.

A snapshot of antimicrobial resistance in Mexico. Results from 47 centers from 20 states during a six-month period.

AIM: We aimed to assess the resistance rates of antimicrobial-resistant, in bacterial pathogens of epidemiological importance in 47 Mexican centers. MATERIAL AND METHODS: In this retrospective study, we included a stratified sample of 47 centers, covering 20 Mexican states. Selected isolates considered as potential causatives of disease collected over a 6-month period were included. Laboratories employed their usual methods to perform microbiological studies. The results were deposited into a database and analyzed with the WHONET 5.6 software. RESULTS: In this 6-month study, a total of 22,943 strains were included. Regarding Gram-negatives, carbapenem resistance was detected in ≤ 3% in Escherichia coli, 12.5% in Klebsiella sp. and Enterobacter sp., and up to 40% in Pseudomonas aeruginosa; in the latter, the resistance rate for piperacillin-tazobactam (TZP) was as high as 19.1%. In Acinetobacter sp., resistance rates for cefepime, ciprofloxacin, meropenem, and TZP were higher than 50%. Regarding Gram-positives, methicillin resistance in Staphylococcus aureus (MRSA) was as high as 21.4%, and vancomycin (VAN) resistance reached up to 21% in Enterococcus faecium. Acinetobacter sp. presented the highest multidrug resistance (53%) followed by Klebsiella sp. (22.6%) and E. coli (19.4%). CONCLUSION: The multidrug resistance of Acinetobacter sp., Klebsiella sp. and E. coli and the carbapenem resistance in specific groups of enterobacteria deserve special attention in Mexico. Vancomycin-resistant enterococci (VRE) and MRSA are common in our hospitals. Our results present valuable information for the implementation of measures to control drug resistance.