Biomarker Turnaround Times and Impact on Treatment Decisions in Patients with Advanced Non-Small Cell Lung Carcinoma at a Large Canadian Community Hospital with an Affiliated Regional Cancer Centre.

Background: Timely reporting of molecular biomarkers is critical in guiding optimal treatment decisions in patients with advanced non-small cell lung carcinoma (NSCLC). Any delays along the tissue or treatment pathway may be associated with suboptimal treatment/outcomes and a reduced quality of life. For many centres, biomarkers are tested off-site. Methods: A retrospective chart review of 123 patients with advanced NSCLC seen between 1 June 2021 and 30 June 2022 was conducted. With a focus on core biomarkers (PD L1, EGFR, and ALK), the outcome variables were as follows: total turnaround time (total TAT), divided into pre-laboratory, laboratory, and post-laboratory time intervals, as well as time to treatment decision (TOTD) and time to optimal systemic therapy decision (TOTSD). Results: At first consult, only 20.3% of patients had all core biomarker results available. The median total TAT was significantly longer for non-squamous (non-SCC) than squamous cell carcinoma (SCC) specimens (36.5 versus 22 days, p < 0.001). The median pre-laboratory time for the entire cohort was 5 calendar days. The median laboratory testing time was greater for non-SCC compared to the SCC specimens (23 versus 12 days, p < 0.001). The median time from consult to TOTD was 19 calendar days for the entire cohort. Conclusions: This study emphasizes the need for the expansion of regional resources to meet the clinical needs of advanced NSCLC patients treated at a regional cancer centre which uses an off-site molecular laboratory.

Contemporary Systemic Therapy Intensification for Prostate Cancer: A Review for General Practitioners in Oncology.

Prostate cancer accounts for a significant proportion of cancer diagnoses in Canadian men. Over the past decade, the therapeutic landscape for the management of metastatic prostate cancer has undergone rapid changes. Novel strategies use hormonal agents, chemotherapy, homologous recombination repair inhibitors, and radioligand therapy or combination strategies in addition to androgen deprivation therapy. In this review, we summarize the available data addressing key therapeutic areas along the disease continuum and focus on practical aspects for general practitioners in oncology managing patients with metastatic prostate cancer.

Metformin in Combination With Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer: The OCOG-ALMERA Randomized Clinical Trial.

IMPORTANCE: Unresected locally advanced non-small cell lung cancer (LA-NSCLC) shows poor survival outcomes even after aggressive concurrent chemoradiotherapy. Whether metformin, a diabetes agent that inhibits the mitochondria oxidative phosphorylation chain, could improve radiotherapy and chemotherapy response in LA-NSCLC remains to be studied. OBJECTIVE: To examine whether metformin, given concurrently with chemoradiotherapy and as consolidation treatment, could improve outcomes in patients with LA-NSCLC. DESIGN, SETTING, AND PARTICIPANTS: The Ontario Clinical Oncology Group Advanced Lung Cancer Treatment With Metformin and Chemoradiotherapy (OCOG-ALMERA) study was a multicenter phase 2 randomized clinical trial. Patients were stratified for stage IIIA vs IIIB LA-NSCLC and use of consolidation chemotherapy. The trial was designed to enroll 96 patients with unresected LA-NSCLC who did not have diabetes. The trial was conducted from September 24, 2014, to March 8, 2019. INTERVENTIONS: Patients were randomized to platinum-based chemotherapy, concurrent with chest radiotherapy (60-63 Gy), with or without consolidation chemotherapy or the same treatment plus metformin, 2000 mg/d, during chemoradiotherapy and afterward for up to 12 months. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients who experienced a failure event (ie, locoregional disease progression, distant metastases, death, and discontinuation of trial treatment or planned evaluations for any reason within 12 months). Proportions were compared using a 2-sided Fisher exact test. Conventional progression-free and overall survival were estimated using the Kaplan-Meier method. Adverse events were graded with Common Terminology Criteria for Adverse Events, version 4.03. All randomized patients were included in an intention-to-treat analysis. RESULTS: The trial was stopped early due to slow accrual. Between 2014 and 2019, 54 patients were randomized (26 in experimental arm and 28 in control arm). Participants included 30 women (55.6%); mean (SD) age was 65.6 (7.6) years. Treatment failure was detected in 18 patients (69.2%) receiving metformin within 1 year vs 12 (42.9%) control patients (P = .05). The 1-year progression-free survival rate was 34.8% (95% CI, 16.6%-53.7%) in the metformin arm and 63.0% (95% CI, 42.1%-78.1%) in the control arm (hazard ratio, 2.42; 95% CI, 1.14-5.10) The overall survival rates were 47.4% (95% CI, 26.3%-65.9%) in the metformin arm and 85.2% (95% CI, 65.2%-94.2%) in the control arm (hazard ratio, 3.80; 95% CI, 1.49-9.73). More patients in the experimental arm vs control arm (53.8% vs 25.0%) reported at least 1 grade 3 or higher adverse event. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the addition of metformin to chemoradiotherapy was associated with worse treatment efficacy and increased toxic effects compared with combined modality therapy alone. Metformin is not recommended in patients with LA-NSCLC who are candidates for chemoradiotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02115464.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019 was held in Morell, Prince Edward Island, 19-21 September 2019. Experts in medical oncology, radiation oncology, and surgical oncology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of anal, colorectal, biliary tract, and gastric cancers, including: radiotherapy and systemic therapy for localized and advanced anal cancer; watch and wait strategy for the management of rectal cancer; role of testing for dihydropyrimidine dehydrogenase (DPD) deficiency prior to commencement of fluoropyrimidine therapy; radiotherapy and systemic therapy in the adjuvant and unresectable settings for biliary tract cancer; and radiotherapy and systemic therapy in the perioperative setting for early-stage gastric cancer.

Ensayo pictórico: descripción del posicionamiento del túnel femoral en distintas técnicas de reconstrucción del ligamento cruzado anterior (lca) / Pictory essay: description of the positioning of the femoral tunnel in different techniques of reconstruction of the anterior cruciate ligament

En la práctica radiológica habitual el radiólogo se encuentra frecuentemente con distintas técnicas de reconstrucción del LCA que debe conocer de manera general para una adecuada descripción e interpretación de los hallazgos. En el presente ensayo pictórico exponemos diferentes tipos de técnica de reconstrucción del LCA, con énfasis en el concepto de reconstrucción anatómica, presentando distintas posiciones del túnel femoral, buscando entregar herramientas al radiólogo para reconocer la normalidad postoperatoria e interpretar posibles complicaciones.

In daily radiological practice, we frequently fid different ACL reconstruction techniques, which we must know in order to achieve adequate interpretation of the fidings. In this pictorial essay, we show different types of LCA reconstruction techniques, highlighting the anatomical reconstruction concept and presenting different positions of the femoral tunnel, seeking to deliver tools to the radiologist in order to recognize the normal postoperative fidings and possible complications.

Systemic Therapy Outcomes in Adult Patients with Ewing Sarcoma Family of Tumors.

BACKGROUND: The Ewing sarcoma family of tumors (ESFT) is a rare but curable bone neoplastic entity. The current standard of care involves chemotherapy and local disease control with surgery or radiation regardless of the extent of disease at presentation. Data that document the effectiveness of the current approach in the adult patient population are limited. METHODS: We performed a retrospective review including all ESFT patients older than 19 years of age who received systemic therapy between January 2002 and December 2013 at our institution. The main study outcome was overall survival; secondary outcomes were objective response rate, disease-free survival, and progression-free survival. RESULTS: Eighteen patients with ESFT were identified. The median overall survival for the entire group was 20.65 months (range 0.43-114.54). In patients with localized disease, the 1-, 2-, and 3-year survival rates were 90, 80, and 70%, respectively. Age was not correlated with overall survival (r = 0.58, p = 0.76). The 3-year disease-free survival rate was 70%. In patients with metastatic disease, the 1-year survival rate was 40%. In patients treated in the neoadjuvant and palliative setting with chemotherapy, we observed an objective response rate of 61.54%. The time to progression in patients with metastatic disease treated with chemotherapy ranged from 0.69 to 4.93 months. CONCLUSION: In this group of adult patients with ESFT treated with multimodality therapy, the outcomes were similar to those reported in well-known larger clinical trials that typically included younger patients. Age was not associated with worse survival.

Media Reporting of Practice-Changing Clinical Trials in Oncology: A North American Perspective.

INTRODUCTION: Media reporting of clinical trials impacts patient-oncologist interactions. We sought to characterize the accuracy of media and Internet reporting of practice-changing clinical trials in oncology. MATERIALS AND METHODS: The first media articles referencing 17 practice-changing clinical trials were collected from 4 media outlets: newspapers, cable news, cancer websites, and industry websites. Measured outcomes were media reporting score, social media score, and academic citation score. The media reporting score was a measure of completeness of information detailed in media articles as scored by a 15-point scoring instrument. The social media score represented the ubiquity of social media presence referencing 17 practice-changing clinical trials in cancer as determined by the American Society of Clinical Oncology in its annual report, entitled Clinical Cancer Advances 2012; social media score was calculated from Twitter, Facebook, and Google searches. The academic citation score comprised total citations from Google Scholar plus the Scopus database, which represented the academic impact per clinical cancer advance. RESULTS: From 170 media articles, 107 (63%) had sufficient data for analysis. Cohen's κ coefficient demonstrated reliability of the media reporting score instrument with a coefficient of determination of 94%. Per the media reporting score, information was most complete from industry, followed by cancer websites, newspapers, and cable news. The most commonly omitted items, in descending order, were study limitations, exclusion criteria, conflict of interest, and other. The social media score was weakly correlated with academic citation score. CONCLUSION: Media outlets appear to have set a low bar for coverage of many practice-changing advances in oncology, with reports of scientific breakthroughs often omitting basic study facts and cautions, which may mislead the public. The media should be encouraged to use a standardized reporting template and provide accessible references to original source information whenever feasible.

Interacciones tempranas madre-niño y predicción de desarrollo motor mediante ecuaciones estructurales: Aplicación del modelo en niños con riesgo de daño neurológico perinatal / Mother-child interactions and early motor development prediction using structural equation: Application of the model in children with perinatal risk of neurological damage

Los impactos más importantes de las expresiones tempranas del daño neurológico en los niños, son las dificultades para establecer intercambios con su medio social, afectando en la etapa inicial las primeras interacciones con su madre. Niños con riesgo biológico muestran grandes dificultades para iniciar interacciones. Cuando las madres se ajustan en una relación bidireccional se logra un aumento en las iniciaciones del niño; si las madres responden menos, los niños disminuyen las iniciaciones y aumentan la irritabilidad. Los programas de intervención temprana que integran en sus estrategias el manejo de las interacciones madre-niño se han considerado exitosos por sus implicaciones directas en el desarrollo del niño. Se requiere mayor soporte empírico sobre la influencia de patrones específicos de interacciones tempranas madre-hijo y el desarrollo posterior de niños con daño neurológico perinatal, en términos de prevención de alteraciones o discapacidad. Se realizó un estudio longitudinal y se reporta el efecto de las interacciones de reciprocidad madre-hijo en el desarrollo motor observado en niños a los 4, 8 y 12 meses de edad, a través del empleo del Modelo de Ecuaciones Estructurales (Curva de Crecimiento Latente). Se concluye que el modelo permitió mostrar que en niños de riesgo perinatal, las interacciones madre-hijo representan un buen predictor del desarrollo motor en el primer año de vida. Estos hallazgos tienen importantes implicaciones en la práctica clínica como estrategia integral para el diseño de acciones de intervención temprana debido a que los logros motores en los primeros meses representan un indicador predictivo del desarrollo infantil posterior.

The most important impact of early expressions of neurological damage in children is the difficulty of mixing up in their social environment which at the beginning affects their interactions with their mother. Children with biological risks show great difficulties to begin interactions. When mothers get adjusted to bidirectional relations with neurologically damaged children, an increase in the commencement of interactions by a child is achieved, while fewer responses of the mother to child produce fewer interactions and increases irritability. Early intervention programs which contain in their strategies management of mother-infant interactions have been considered effective for child development. However, further empirical studies are required, concerning the influence of specific patterns of early mother-infant interaction and future development of children with perinatal neurological damage, in terms of prevention of alterations or disability. The present longitudinal study reports the effect of reciprocity of mother-infant interactions in the motor development observed in children of 4, 8, and 12 months old, latent growth curve in structural equation modeling. This model permits the identifications of causal factors that could affect the results in different age groups and provides predictions of the relations in a more complex form than lineal relations. Based on the model designed, it could be shown that mother-infant interactions of reciprocity best characterized children with higher development level while the absence is seen in children with retarded development. We classified mothers and children in two types, respectively: interactive and organized mothers vs. non-interactive and disorganized ones; interactive and responsive children vs. non-interactive and non-responsive ones. Subjecting these two types of mothers and children to four possible combinations, the model results showed different motor development predictions in the children. On one hand, we estimated regression coefficient of four dyadic systems, obtained by combinations of different types of mothers and children: interactive and organized mother with interactive and responsive child (Dyadic system 1); interactive and organized mother with non-interactive and non-responsive child (Dyadic system 2); non-interactive and disorganized mother with interactive and responsive child (Dyadic system 3); and non-interactive and disorganized mother with non-interactive and non-responsive child (Dyadic system 4). Dyadic system 1 was associated with a better motor development in children with a mayor regression coefficient (19.82), followed by System 2 and System 3 (regression coefficient of 17.54 and 11.46, respectively). System 4 had a negative estimate value of regression coefficient (-11.27) in our model. On the other hand, we estimated intercept values according to the interactive type of these mothers and children. Among the four interactive types, solely two of them had statistically significant intercepts (p < .05), or = 66.13 for interactive children and or = 42.76, for non-interactive children. To predict the motor development of 4, 8, and 12 months old children, the slope with attenuation permitted to give a mayor model fitting, with the regression coefficient of 0, 1 and 1.5, respectively. This model presented excellent values of model fitting indicators (X² = .96, p = .97, CFI = 1.00, RMSEA = .00). This line of study should be widened, because motor development is the principal domain consolidated in the first months of life. It is fundamental in domain organizations of higher complexity as cognition and language. We conclude that this model showed that in high risk perinatal children, early mother-child interactions represent a good predictor of motor development in the first year of life. Moreover, we found that motor achievements in the first months of life can be a strong predictive indicator of future development of a child. These findings suggest the importance in clinical practice of observation and registration of mother-child interactions as part of an integral strategy of child evaluation.

Los movimientos elementales complejos del humano: Desarrollo postnatal. Reporte preliminar de nueve lactantes mexicanos / The complex elementary human movements: Normal postnatal development. Preliminar report of nine Mexican infants

Introduction The study of the early neonatal and infant behavior has called the attention of several researchers with the purpose of establishing an early diagnostic of neurological damage. Ferenc Katona identifies, from the 28th week of gestation to the third month of extrauterine life, a group of locomotion and verticalization innate behaviors which are called Complex Elementary Movements (CEM). These sequences of generalized motor activity of central origin, with automatic movements, generate sensory impulses to the spinal cord, brainstem and superior systems in response to gravitational and acceleration stimulus. These impulses cause continuous and repetitive movements of the head, trunk and limbs, and lead to verticalization and locomotion. They also prefigure the human behavior by organizing structures and cerebral functions ontogenetically mature at birth and with greater resistance to damage. In normal European neonates and infants, the constancy and stability has allowed for the diagnose of early Nervous System dysfunction (SN). European researchers have applied procedures that include CEM for neurohabilitation. Katona explains that when CEM are induced, they stimulate the vestibular system performance. The repetitive and/or sustained muscular contractions of trunk and extremities during the attempts of verticalize or locomotion, transmit new stimulus that strengthen the initial stimulation. During the time that the infant maintains the pattern activation, the thalamus, basal ganglia and cerebral cortex are stimulated, simultaneously and proportionally, occurring changes in the muscular tone, the movement dynamics and posture within a critical period of cerebral plasticity. The movements of head, trunk and extremities are refined or reorganized as in normal child maturity (development). This prevents and avoids risks and altered functions. In Mexico, according to the information sources reviewed, there are no studies describing the normal postnatal development variations. It is important to differentiate normal movements from the pathological ones to make early diagnosis of neurological damage in Mexican populations. Material and methods The Tlalpan outpatient family medicine clinic of the Institute of Security and Social Services for State Employees (ISSSTE) referred 25 infants, considered with low perinatal biological risk, residents of Mexico City. The Heinz Prechtl neurological sieve was applied to each infant to confirm an adequate neurological maturity. Fifteen infants fulfilled the inclusion criteria, the parents of nine infants agreed on their child participation in four evaluations, scheduled monthly, according to the day of birth. The parents signed the informed consent letter. In each evaluation, the ten maneuvers of activation were applied twice. They were distributed 6 at the first month, 9 at 2 and 3 months, and 8 at 4 months. Five maneuvers were applied to activate locomotion: Mcgraw, Bauer, reinforced Bauer, crawling on an inclinate slide and assisted crawling. Also five maneuvers were put into practice for verticalization: carry sitting, antigravity verticalization, stand up reaction, elementary walking and sitting in the air. Five behaviors and movements were described: crying, visual behavior (eyes closed or open with or without visual fixation), limbs, trunk and head movements. The evaluations were recorded in 8mm digital format and reviewed instantly during the evaluation. The camera's timer was used to measure the time they took to activate movements of locomotion or verticalization. To calculate frequencies and central tendency measures, the SAS statistical software JMP, version 7.0 was used. Results 320 activating maneuvers were used, 82.5% activated locomotion and 58% verticalization. The children awoked spontaneously with rude movements and cried, in 63% of the evaluations including the five locomotion patterns: 58.7% in the Alternating Cross Pattern (ACP), 10% for the Incomplete Simultaneous Pattern (ISP), 10% in the Lower Limb Alternating Pattern (LLAP), 1.25% on Complete Simultaneous Pattern (CSP) 2.5% and Homolateral Pattern (HP). The most frequent pattern observed was the Alternate Cross Pattern (PAC) 58.7% and the less frequent was the Homolateral Pattern (PH) 1.25%. In verticalization two patterns were observed: 58% with complete trunk and head alignment, 42% with incomplete alignment. The latencies to enable MEC were from 0-120 seconds, with M 27.7, DE ±48.8 for locomotion and M 9.43, DE ±20.7 for verticalization. Opening the eyes and visual fixation in the locomotion maneuvers occurred in the 43%, 20% in the first month, 31% in the 2nd month, 42% in the 3rd month and 75% in the 4th month. Verticalization maneuvers occurred in 64%, 47% in the first month, 49% in the second month, 64% in the 3rd month and 95% in the 4th month. As the children grew, the open eye and visual fixation conducts increased in presence. Locomotion appeared in the 43% of the children and verticalization in 64%. Discussion Katona reports that the MEC activation is given from birth to three months, with exception in two maneuvers: crawling on an inclined slide that appears until two months and on the four month the manifestation of elementary march. In this research, the locomotion and ver-ticalization patterns appeared sometimes until the fourth month, with frequencies that change in 12% to 100% of the cases according to the maneuvers form. Two patterns were identified but not described, the PH with a case frecuency of 1.25% and the PSC with 2.5%. Katona suggested that infants up to three months old are able to activate several seconds to complete verticalization, due to vestibular activity. In our experience, until two months they are mainly short and incomplete patterns of vertical integration then completed and sustained during the third and fourth month. Concerning the time required to activate MEC, Katona reported latencies of 5-100 sec. with absence of responses until the 4th month. Except for elementary walking, we observed that the latency time varies with age. In this investigation the locomotion time was 27.7 sec average, founding 0-120 sec intervals. In verticalization, latencies were faster than the average latency time of 9.43 sec. With intervals of latency in the first two months of age of 0-19 sec. elementary walking and the stand up reaction with age took but in activating and to the fourth month in several cases no longer they appeared. Katona reported that the newborn is capable of a brief visual fixation with the presentation of the face or with a flashing object 20cm away. The results of the locomotion and verticalization maneuvers showed that the behavior was present in the first month, in less of the 50% locomotion assessments and in less of 70% in verticalization. When the maneuver allowed controlling the head or maintaining the face to face line sight, the infant opened and fixed visually. Conclusions In the nine Mexican infants explored, variations were reported in the postnatal MEC evolution, with respect to the age of appearing, patterns type, trunk and limbs movements, time required for activation (latencies), visual activity and crying presence were not observed. If these variations are confirmed we could establish more accurate reference parameters and analyze their relationship with biological and environmental factors. Thus, to strengthen a prevention method in neurohabilitation/neurorehabilitation for high-risk population benefit.

Introducción Con el propósito de diagnosticar tempranamente el daño neurológico, Ferenc Katona identifica desde la semana 28 de gestación hasta los tres meses de vida extrauterina un grupo de comportamientos innatos de locomoción y verticalización, a los cuales se les denomina Movimientos Elementales Complejos (MEC). Son secuencias de actividad motora generalizada automática de origen central provocadas por estímulos gravitacionales y de aceleración. Su activación genera impulsos sensoriales al cordón espinal, al tallo cerebral y a los sistemas superiores, lo que resulta en movimientos continuos y repetidos de la cabeza, del tronco y de las extremidades dirigidos a la verticalización y a la locomoción. La constancia y estabilidad en la normalidad de los MEC en neonatos y lactantes europeos ha permitido diagnosticar la disfunción temprana del Sistema Nervioso (SN) y utilizarlos como procedimientos de neurohabilitación. En México, con base en las fuentes de información revisadas, no hay estudios que describan las variaciones del desarrollo normal postnatal por lo que es importante conocerlas y tener un referente para diferenciar las normales de las patológicas. Material y métodos La consulta externa de la Clínica de Medicina Familiar Tlalpan, del Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE), refirió 25 lactantes considerados de bajo riesgo perinatal, a quienes se les aplicó el Tamiz neurológico de Heinz Prechtl para confirmar una adecuada madurez neurológica. Quince de los lactantes cumplieron con los criterios de inclusión. Los padres de nueve lactantes aceptaron llevar a sus hijos a las cuatro evaluaciones programadas mensualmente de acuerdo al día en que nacieron y firmaron la carta de consentimiento informado. En cada evaluación se aplicaron dos veces las diez maniobras de activación (cuadro 1). Las variables de estudio son: presencia de llanto, comportamiento visual, movimientos de extremidades, tronco y cabeza. Las valoraciones se filmaron en formato digital de 8mm. El cronómetro de la cámara midió el tiempo que tomaba cada maniobra en activar los movimientos (latencia). Se utilizó el programa estadístico JMP de SAS, versión 7.0, para el cálculo de frecuencias y medidas de tendencia central. Resultados Se provocaron 320 maniobras, de las cuales se activaron 82.5% en locomoción y 58% en verticalización. El 63% de los niños estuvieron despiertos con movimientos groseros y llanto. De los patrones de locomoción, el de mayor frecuencia fue el Patrón Alterno Cruzado (PAC), con 58.7%, y el de menor frecuencia fue el Patrón Homolateral (PH), con 1.25%. En la verticalización, su presencia fue de 58%, con alineación completa del tronco y la cabeza, y 42% con alineación incompleta. Se obtuvieron latencias de activación, para la locomoción, entre 0-120 segundos, con una media de 27.7±48.8 y para la verticalización una media de 9.43±20.7. El comportamiento visual, abrir ojos y fijación visual aumentó conforme el niño crecía. Discusión Katona reporta que la activación de los MEC se presenta al nacimiento y hasta los tres meses, con excepción de dos maniobras: gateo en plano inclinado, presente hasta los dos meses, y marcha elemental que se observa hasta el cuarto mes. En esta investigación, los patrones para locomoción y verticalización pudieron provocarse hasta el cuarto mes con frecuencias que variaron de un 12% a un 100%, de acuerdo al tipo de maniobra. Se identificaron dos patrones no descritos: el PH, con 1.25%, y el Patrón Simultáneo Completo (PSC), con 2.5%. La verticalización completa apareció y aumentó en frecuencia con la edad en nuestra población. En cuanto a la locomoción se obtuvieron variaciones en el movimiento de las extremidades, el tronco y el tiempo de latencia. Cuando la maniobra permitió controlar la cabeza o mantener la línea de la mirada frente a frente, el lactante abrió los ojos y fijó visualmente. Conclusiones Se documento la variabilidad de los MEC en niños mexicanos de bajo riesgo, mostrando que éstos evolucionan desde patrones de menor verticalización, con llanto frecuente y escasa fijación visual al nacimiento a patrones de verticalización completa, mayor fijación y disminución del llanto, lo cual comprende una modificación al criterio de calificación propuesto por los autores para niños europeos. Los ajustes al procedimiento tienen implicación en la detección temprana de riesgos para la discapacidad motriz.

Análisis del llanto en niños hipoacúsicos y normoyentes de 0 a 2 años de edad

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Abstract: Infant crying is a complex phenomenon that implies several functions: breathing, action of laryngeal and supralaryngeal muscles under the control of the neurovegetative systems of the brainstem, and the limbic system, and the association of cortical areas and the cerebellum. Although it is a communication system different to babbling and language, it is related with the future development of phonation. Cry analysis provides information about the neuro-physiologic and psychological states of newborns and the identification of perinatal abnormalities. It is necessary to discuss the subject extensively because there are new data on situations such as laringomalacia, congenital hypothyroidism, deafness and sleep apnea that seem to be associated to infantile crying behaviors. Infant cries can be analyzed as behavioral conditions (hunger, anger and pain cries) allows knowing of mother-child relationship or the effect under diverse cultural conditions, such as stress, emo-tional deprivation or illness. A spectrographic analysis of the cries may identify several characteristics: threshold, latency, duration of phonation, maximum and minimum of the fundamental frequency (F0), occurrence and maximum pitch of shift, gliding, melody, biphonation, bifurcation, noise concentration, quality of the voice, double harmonic break, glottal plosives, vibratos, melody types, F0 stability and inspiratory stridor. To date, it has not been possible to establish alteration patterns. The best studied variables are F0, its harmonics and the duration of each emission; it is accepted that F0 varies between 400 and 600 Hz, during 1.4 ± 0.6s. Under such approaches, diverse alterations and risk factors have been studied: congenital alterations, malnutrition, sudden death, maternal exposition to drugs, prematurely born babies or perinatal asphyxia and disturbances of the central nervous system. Authors have reported F0 equal or less than 300 Hz in cases of sudden death or with high frequencies, near the 1000 Hz in the Cri du chat syndrome, perinatal asphyxia and other cases who died suddenly. During the cry, there is an increase of intra-abdominal pressure, heart rate and blood pressure, reduction of oxygen saturation, increase of the intra cranial-pressure, beginning of stress reactions, depletion of the energy anf oxygen reserves, such as the found in the Valsalva's maneuver. Every event of prolonged cries implies alteration of the breathing control like a Hering-Breuer reflex. Considering that some authors have proposed early vocalizations are a good predictor of deafness, in a previous paper we reported the characteristics of the cry of 20 deaf neonates. However, we were not able to demonstrate differences when comparing them with normal hearing neonates and infants, using only parametric methods. Still, we decided to go further and investgate the quality of infant cries of deaf neonates and infants. Material and methods. Twenty zero-to two-year old cases were studied; they were deaf children of both sexes; all cases were included in a follow-up program on the Human Communication Department of the National Institute of Perinatology of Mexico and were compared with 20 normal hearing children. We re-corded Brain Stem Evoked Auditory Responses (BEAR) and cry recording using a digital Sony recorder during the physical exploration. We analyzed the frequency (Hz) and duration of the espiratory cries, the duration of inspiration between two cry emissions and the characteristics of the spectrogram. Quantitative analysis. The usual estimates of means and standard variation were obtained and they were compared with one way analysis of variance. We organized typologies of frequency by means of cluster techniques (Ward method). The distribution of the duration of the periods of crying and silence was explored with a contingency tables. Qualitative analysis. Two standardized observers visually analyzed all the cries to determine any variation of F0 and of harmonic frequencies. Whenever a variation of F0 was observed, we obtained maximum and minimum frequencies, as well as average duration of each cry emission. The procedure was validated by means of the graphic comparison with a Fouries analysis. Results. Mean duration of cries in the deaf group was 0.5845 ± 0.6150 s (range 0.08-5.2 s), while in the group of normal hearing cases was 0.5387 ± 0.2631 (range 0.06-1.75 s). From the deaf group, five cases had very prolonged duration of cries, without statistical significance. The mean duration of the inspiration was 0.3962 ± 0.2326, with a range of 0.06 to 1.75 in the deaf group and of 0.4083 ± 0.1854, with a range of 0.21 at 0.96, in the controls, without difference among groups. There was no correlation between the time of espiratory cry and that of the inspiration. Three cry topologies were organized: one of shorter duration (mean 0.30 s), with 111 spectrograms, an intermediate one (mean 0.73) with 85 spectrograms and one of prolonged duration (mean 4.5 s) with spectrograms of three cases. Three topologies of the inspiratory period were obtained: one of short periods (mean 0.33 s), with 171 spectrograms, one of intermediate duration (mean 0.80 s) with 18 spectrograms and one of prolonged duration (mean 1.60 s) with three cases. There were no statistical differences of tipologies between the deaf groups and normal hearing cases. On the qualitative analysis of cries, we came across several variations which are interpreted as abnormalities: vibratos, poor melodic control, loss of fundamental frequencies, harmonic limited production, plosives, gliding, bi phonation, and a loss of intensity at end of cry emissions. These changes were also observed on the control cases, but only in a very limited number. Discussion. Cry spectrogram analysis are non invasive indicators of the neonate's neurophysiologic organization. Although cry duration varies in healthy newborns, the accepted variation for a normal range is 1.1 to 2.8 s, with standard deviations around 0.6 s. Consistent differences have not been demonstrated between risk and control groups. However, abnormal cases such as Down syndrome or severe asphyxia have very short cries, whereas on the Cri du chat syndrome the duration of cries is prolonged. Extended cries imply cardiac and respiratory risks which have been associated with later outcomes as development retardation and sudden death. There are also some questions to solve, such as the regulation and control of cry, starting from breathing mechanisms or from a sensorial afferent, mediated by hearing. The deaf infants are constituted in a study model, considering that the auditory afference is suppressed and the control of the cry is restricted to the breathing environment. In the studied spectrograms, the duration of the cry was within reported normal limits by other authors, inasmuch in the normal hearing control cases as in the deaf, except the dissident cases, but without these reaching statistical significance. Further research of brainstem function is needed for the abnormal cases with prolonged cry periods, since such cries are interpreted as an alteration of the breathing reflexes of Hering-Breuer, which might have a pathological meaning in the sense of the sob's spasm or even more severe risk factors as sleep apnea and even sudden death. The qualitative analysis in the deaf individuals demonstrated a poor quality and unstable character of melodic control, with a smaller number of harmonics. The deaf cases lost the relationship between the fundamental frequencies and their harmonics, mainly because of the participation of supraglottic structures that modulate pitch and due to the poorness of melodic control, either for monotony or due to the impossibility of returning to a normal pattern, following variations such as vibrato, plosives or noise concentration. In the cases of prolonged cries, starting from the third second, the sound intensity tends to diminish and the harmonics are lost, perhaps due to a decrease of the subglottal pressure of phonation. This finding supports the auditory control of crying related to breathing mechanisms. Conclusions. In preliminary terms, by means of the melodic analysis of the spectrograms, differences are demonstrated be-tween the cries of the deaf and of the normal hearing cases. The increase of the complexity of the melody of the cry, or their poverty, are indicative of the neuromuscular function and they may support the evaluation of phonation before language development. The study of the spectrograms of deaf individuals does not constitute an element for the detection or for diagnosis since, to date, estimators of sensibility or of specificity have not been established, but they constitute a support for its integral evaluation, with the possibility of evaluating and of improving therapeutic rehabilitation.

Laringomalacia en una cohorte de seguimiento del desarrollo infantil por antecedentes de encefalopatía perinatal: Implicaciones para su conceptualización nosológica / Laryngomalacia in a Follow-Up of a Child Development Cohort for Antecendents of Perinatal Encephalophaty: Implications for Nosologic Conceptualization

Se presenta el análisis retrospectivo de 10 casos de estridor laríngeo congénito. Se discuten algunos reportes de endoscopios laríngeas con los diagnósticos elaborados. Se define la laringomalacia como una entidad caracterizada por flacidez laríngea y estridor. Algunos autores postulan, además de la inmadurez de los tejidos, la posibilidad de incoordinación laríngea y disquinesia. Se apoyan en casos de presentación tardía, de daño neurológico y casos atípicos relacionados con estado funcional o con anestesia Se realizaron endoscopios en 10 casos provenientes de una cohorte de seguimiento longitudinal de casos con diagnóstico de daño neurológico perinatal que se atienden en el Laboratorio del Seguimiento del Neurodesarrollo, del Instituto Nacional de Pediatría/Universidad Autónoma Metropolitana. En un caso se diagnosticó parálisis unilateral de cuerda vocal, postoperatoria. Un caso tuvo anillo vascular, Los ocho casos restantes cubrieron los criterios de laringomalacia, pero por sus características se insiste en que no se trata de una alteración anatómica idiopática sino de una hipotonía funcional. Se enfatiza la necesidad de realizar estudio integral y describir la comorbilidad.

We conducted a retrospective analysis of 10 cases of congenital laryngeal stridor. Reports of laryngeal endoscopy and diagnosis define laryngomalacia as laryngeal flaccidity and stridor. Some authors postulate that in addition to immaturity of cartilage, there exist the possibility o flaryngeal uncoordination and dyskinesia. They support this idea in cases of late presentation, neurological damage, and atypical cases related with functional state or anesthesia. Laryngeal endoscopies were carried out in 10 cases included in a cohort of subjects from a longitudinal follow-up diagnosed with neurologica damage of perinatal origin. One case was diagnosed with postoperative unilateral paralysis of vocal chord and another identified vascular ring. The eight remaining cases fulfilled laryngomalacia criteria of diagnosis, but because of their characteristics origin is not an anatomic alteration but a functional hypotonia. The need to carry out an integral study to describe co-morbidity is emphasized.

Estado nutricional de hierro en Guatemala: realidades y perspectivas, análisis de los estudios realizados en Guatemala de 1960 a 2000 / Iron nutritional status in Guatemala: issues and perspectives, analysis of data obtained in Guatemala between 1960 and 2000

Con el objetivo de analizar la información disponible acerca del estado nutricional de hierro en Guatemala para caracterizar su situación e identificar líneas de investigación, se hizo un estudio con diseño de metanálisis, que comprendió cinco fases: recopilación y agrupación de estudios; análisis cualitativo; análisis e integración de estudios; e identificación de necesidades de investigación. Se recopilaron 113 estudios, publicados o no, acerca del estado nutricional de hierro en sujetos guatemaltecos. Se encontró que la información relacionada con estos estudios se encuentra dispersa y a veces de difícil acceso; asimismo se evidencia que no existe un consenso acerca de los criterios de normalidad acerca de los indicadores utilizadas en estas investigaciones. Aunque los únicos datos de todos los grupos de edad a nivel nacional datan de 1969, es claro que la deficiencia de hierro es un problema de gran magnitud en Guatemala. Los grupos más esudiados son el de preescolares y el de mujeres en edad fértil. Emergen como grupos importantes a investigar el de los lactantes, adolescentes de ambos sexos, adultos y adultos mayores. Se determina que el patrón dietético de los guatemaltecos está cambiando de manera variable, lo cual hace necesario desarrollar diseños que permitan identificar y caracterizar estos cambios. Los programas de suplementación y fortificación con hierro no cuentan con información que de una idea acerca de su cobertura e impacto. Se hacen recomendaciones para reorientar la investigación relacionada con el estado nutricional de hierro

Divertículo duodenal / Duodenal diverticulum

El duodeno es el segundo sitio más común, luego del colon, para la presentación de los divertículos intestinales. Generalmente es asintomático y su hallazgoes incidental durante la cirugía. Puede manifestarsecon ictericia, por compresión extrínseca de la vía biliar o cálculos; así también puede presentarse comopancreatitis. La morbilidad puede ser producida por hemorragia o perforación, hallazgos documentados en 5 por ciento de los casos. El divertículo duodenal es causa poco frecuente de enfermedad del tracto digestivo. Su diagnóstico es accidental durante procedimientos diagnósticos como series gastroduodenales, colangiogramas, tomografías o endoscopías. La terapéutica médico-quirúrgica al tratamiento exclusivamente de las complicaciones. Para el endoscopista el divertículo periampular constituye un factor de riesgo durante el ERCP. Presentamos una revisión de los artículos más importantes que versan sobre el tema incluyendo frecuencia, epidemiología, métodos diagnósticos, tratamiento quirúrgico, morbilidad, mortalidad y pronóstico. Los aspectos considerados en este artículo orientan al clínico, cirujano, gastroenterólogo y endoscopista en su investigación diagnóstica

Las secuelas neurológicas de origen perinatal en su relación con los factores de riesgo. Modelo de estudio / Neurological sequels of perinatal origin and factor risk. A model to study

Antecedentes. Se postula la importancia de las secuelas neurológicas de origen perinatal. Se revisa la definición de secuela, insistiendo en considerarla como un proceso que se desencadena a partir de ciertos factores de riesgo que la condicionan, para poder abordar el problema a partir de los factores de riesgo y establecer pogramas que prevengan los síndromes de parálisis cerebral, retardo mental y alteraciones de conducta. Objetivo. Señalar la insuficiencia de los procedimientos estadísticos descriptivos y univariados, y proponer el empleo de modelos complejos de análisis. Material y métodos. Se presentan algunos datos publicados en la literatura relativos a la frecuencia de presentación de secuelas y finalmente se expone el programa de la Clínica de Neurodesarrollo del Instituto Nacional de Pediatría-Universidad Autónoma Metropolitana, Unidad Xochimilco. Resultados. Mediante los procedimientos estadísticos descriptivos y univariados no se comprueba la asociación entre factores de riesgo como peso, condición al nacimiento, edad gestacional y datos del diagnóstico de la encefalopatía por US cerebral, EEG, potenciales evocados, exploración clínica neurológica y los datos de los casos y desarrollo posterior de secuelas. Con análisis complejos sí se demuestra la asociación y se insiste en que no es directa ni lineal

Detección de las diferentes formas de prolactina por autorradiografía / Detection on the different forms of prolactin by autoradiography

La proteína A Staphylococcus aureus fue caracterizada por electroforesis en geles de poliacrilamida en presencia de sodio dodecil sulfato y marcada radioactivamente con Nal125. El reactivo marcado fue utilizado para el montaje de una técnica autorradiográfica para la determinación de las distintas formas moleculares de la prolactina. La proteína A presentó 2 bandas mayoritarias, con pesos moleculares entre 40 y 42 kDa. La incorporación de Nal125 a la proteína A fue del 88,5 %, y la actividad específica (AE) fue de 63 * Ci/*g. La técnica autorradiográfica fue sensible para detectar diferentes variantes de la prolactina en el plasma de mujeres hiperprolactinémicas. La proteína A-l125 puede ser utilizada con fines diagnósticos o en técnicas biotecnológicas en general

Perfil neurofisiológico del neonato de alto riesgo en seguimiento / Neurophysiologic profile in high risk newborns

Se plantea y evalúa una alternativa para la detección de los niños que tienen riesgo de sufrir secuelas neurológicas de origen perinatal. Se aplicó longitudinalmente la metodología de la exploración neurofisiológica integral a setenta y tres niños que participaron en el Programa de Seguimiento del Instituto Nacional de Perinatología; se caracterizó a los niños como organizados o desorganizados funcionalmente y se relacionaron estas categorías con las de la exploración neurológica clínica, definida como normalidad, sospecha o anormalidad. Los resultados señalan que al nacimiento la evaluación neurofisológica es útil para identificar a los niños con alteración neurológica y que si se toma en cuenta la evaluación funcional durante los primeros tres meses postnatales, es posible identificar a los niños que tienen riesgo de daño con carácter permanente; al relacionar este hallazgo la evolución neurológica durante el primer año, se concluye que ésta es una alternativa para la detección temprana de secuelas neurológicas y se especula sobre el riesgo para secuelas en las áreas del lenguaje, la conducta y el aprendizaje