Ototoxicidad inducida por quimio-radioterapia basada en platinos: una revisión / Ototoxicity induced by platinum compounds-based chemoradiotherapy: a review

RESUMEN Los análogos del platino, como el cisplatino, y la radioterapia son usados de forma individual y en conjunto para el tratamiento de diversas neoplasias en población adulta y pediátrica. Sin embargo, el uso de estos tratamientos puede generar ototoxicidad, especialmente cuando son usados de forma combinada para neoplasias que comprometen cabeza y cuello, manifestándose principalmente como una hipoacusia progresiva e irreversible que compromete la calidad de vida. Diversos mecanismos han sido propuestos para explicar el daño en las estructuras auditivas generado por estos tratamientos, incluyendo la producción de especies reactivas del oxígeno y la inflamación, desencadenando muerte celular. Si bien distintas estrategias otoprotectoras han sido probadas en humanos, es aún incierta su efectividad y seguridad en combinación con los tratamientos oncológicos. El objetivo de la siguiente revisión es proporcionar una visión general y actualizada de la ototoxicidad inducida por quimio-radioterapia basada en platinos, discutiendo sus bases, características clínicas, potenciales tratamientos y estrategias preventivas que se han desarrollado en los últimos años.

ABSTRACT Platinum analogues, such as cisplatin, and radiotherapy are used separately or in combination to treat several neoplasms in pediatric and adult populations. Nonetheless, the use of these treatments may lead to ototoxicity, especially when these treatments are concomitantly used to treat head and neck cancers, which can manifest as progressive and irreversible hearing loss that decreases quality of life. Several mechanisms have been proposed in order to explain the damage to the auditory structures induced by these treatment modalities, including: reactive oxygen species production and inflammation, leading to cell death. Although several otoprotective strategies have been attempted in humans, their effectiveness and security are unclear. The objective of this review is to provide an updated and general overview on platinum-based chemoradio-therapy induced ototoxicity, discussing its basis, clinical features, potential treatments and preventive strategies developed in recent years.

Application of infrared thermography in diagnosing peripherally inserted central venous catheter infections in children with cancer.

APPROACH: Children affected by oncological diseases are often fitted with central venous catheters (CVCs). Catheter infection is a frequent complication, sometimes accompanied by thrombosis. A case/control-type pilot study of children with oncological diseases fitted with a CVC is here designed. OBJECTIVE: The objective of this preliminary study is to use infrared thermography to discern whether there is an infection in patients with a CVC and, if so, to undertake a close follow-up of its evolution, after administering a therapy. Thermal asymmetry by mean and maximum temperatures (temperature affected ROI - temperature contralateral ROI) is measured. MAIN RESULTS: In all cases with catheter infection, thermal asymmetry values were higher than in controls without infection, allowing us to assess improvement after starting the treatment. SIGNIFICANCE: These preliminary results are satisfactory because they reflect the advantages of using infrared thermography on oncological child patients, as it is a harmless, non-contact, accessible and quick technique, allowing us to reduce the use of ionizing radiation and quantify the clinical signs of inflammation, which are otherwise only qualitatively detectable in clinical examination. By doing so, it may be possible to anticipate infection and provide early treatment, and, moreover, to observe whether there is any complication after starting a treatment. More studies need to be undertaken with an extensive paediatric population to establish reference values.

Determinación del caudal ambiental y su relación con variables indicadoras de calidad del recurso hídrico / Enviromental floow determination and its relationship ith water resouurces quality indicator variables

El objeto de esta investigación es la determinación del caudal ambiental en la subcuenca del río Las Piedras y su correlación con diferentes variables fisicoquímicas e índices de calidad del agua. Inicialmente se realizó la determinación del caudal ambiental utilizando una aproximación a la metodología para la determinación del caudal ambiental en proyectos licenciados de Colombia, los cuales son aquellos que de acuerdo con la ley y reglamentos puedan producir deterioro grave a los recursos naturales renovales, al medio ambiente o introducir modificaciones considerables o notorias en el paisaje (MAVDT, 2010). Seguidamente, teniendo el caudal ambiental establecido para cada mes y desglosado por condición hidrológica (Niño, Niña y normal), se procedió a estimar la correlación existente entre estos, medidas in situ (pH, conductividad, OD, turbidez, TDS, T y el factor de asimilación de la corriente) con el fin de hacer una estimación de la calidad del agua que se tendría manteniendo los caudales ambientales propuestos, usando para ello el programa estadístico SPSS. Por otro lado se realizó una evaluación de la integridad biótica, para establecer el estado ecológico de la subcuenca con base en la comunidad de macroinvertebrados. Como resultado se determinó el caudal ambiental para cada mes y las tres condiciones hidrológicas, igualmente se pudo observar la relación directa, existente entre el factor de asimilación de la corriente y el caudal, estableciendo de esta forma que el factor de asimilación puede ser una herramienta que permita la determinación de periodos de mayor vulnerabilidad a eventos extremos que pueda presentar la subcuenca. De igual forma, se consiguió realizar una estimación de las variables físicas (conductividad y TDS) con las cuales el caudal presentó correlación significativa, lo que permite tener una relación idónea entre la cantidad y calidad del recurso hídrico. Adicionalmente, se pudo establecer el estado de la calidad del recurso hídrico de la zona estudiada con base en un estudio realizado de la comunidad de macroinvertebrados como bioindicadores.

The purpose of this research is to determine the environmental flow in the sub-basin of the river “Las Piedras” and its correlation with different physicochemical variables and indexes of water quality. The environmental flow determination using an approximation to the methodology for determining the environmental flow of Colombian licensed projects, which are those that, according to the law and regulations, can lead to severe deterioration to renewable natural resources or introduce significant or noticeable changes in the landscape (MAVDT, 2010) was initially performed. Next, having the environmental flow established for each month and broken down by hydrologic condition (children and Normal) the correlation between these, in-situ measurements (pH, conductivity, DO, turbidity, TDS, T, and absorption factor of the stream) was estimated in order to estimate the quality the water would have maintaining the proposed environmental flows, using SPSS for this purpose. In addition,an assessment of biotic integrity, to establish the ecological status of the watershed based on the macro invertebrate community, was carried out. As a result, the environmental flow for each month and for the three weather conditions was determined. Likewise, the direct relationship between the assimilation factor and the current flow could also be observed thus establishing that the factor assimilation can be a tool that allows the determination of periods of increased vulnerability to extreme events that may occur in the sub-basin. Similarly, it was possible to estimate the physical variables (conductivity and TDS) with which the presented significant correlation, which allows having a suitable relationship between the quantity and quality of water resources. Additionally it was possible to establish the state of the quality of water resources in the studied area based on a study carried out dealing with the macro invertebrate community as bioindicators.

Genetic polymorphisms and other risk factors associated with bisphosphonate induced osteonecrosis of the jaw.

Bisphosphonate induced osteonecrosis of the jaw (BONJ) is a complication in patients taking bisphosphonate (BP) that affects their quality of life and compliance. In this cohort study, patients with multiple myeloma (MM) on intravenous BP therapy were enrolled over 1 year. Demographic and clinical data and genotyping of 10 single nucleotide polymorphisms (SNPs) from seven candidate genes associated with drug or bone metabolism were determined. Of the 78 patients enrolled, 12 had BONJ. The median time to developing BONJ was 28 months. Univariate and multivariate analysis revealed a significant association between BONJ and smoking (p=0.048) and type of BP treatment (p=0.03). A trend for higher odds for BONJ was found for SNPs in five genes: COL1A1 (rs1800012), RANK (rs12458117), MMP2 (rs243865), OPG (rs2073618) and OPN (rs11730582). Considering all five SNPs together, patients with genotype scores ≥ 5 had a BONJ event rate of 57%; those with scores < 5 had a rate of 10%. The adjusted odds ratio was 11.2 (95% confidence interval of 1.8-69.9; p value 0.0097). Smoking, type of BP and combined genotype score of COL1A1, RANK, MMP2, OPG and OPN were significantly associated with BONJ in MM patients undergoing BP therapy.

How fetal cocaine exposure increases neonatal hospital costs.

OBJECTIVE: Our goals were to document hospital costs associated with prenatal cocaine exposure in an understudied population-women using rural county public health units who had minimal access to drug rehabilitation and whose cocaine of choice was crack with little other illicit drug use- and to explore why increased costs occur in an effort to identify cost-reduction strategies. METHODS: We identified a sample of cocaine-exposed infants who were computer-matched to a control group with no history or evidence of cocaine exposure. Matching was performed one-to-one on the variables of maternal race, age, parity, time of entry into prenatal care, and alcohol and nicotine use. There were 327 live births, for whom 311 were correctly classified as to their prenatal cocaine use and had billing and medical records available for review (156 exposed, 155 nonexposed). RESULTS: Hospital charges were positively correlated with length of stay. Cocaine-exposed infants had an across-the-board increase in utilization of hospital resources as well as higher hospital charges and longer lengths of stay. Cocaine-exposed infants were significantly younger in gestational age and lower in birth weight. Significantly more cocaine-exposed infants were admitted to the neonatal intensive care unit, had more social and family problems delaying discharge, and received more septic work-ups. In addition, of those infants urine-screened for cocaine at delivery, 92% were screened secondary to a maternal history of prenatal use. CONCLUSIONS: Cost-reduction strategies should be aimed at measures that reduce length of stay by addressing problems identified prenatally as an outpatient before delivery and by influencing objective decision-making regarding the need for medical interventions with the infant after birth.

Detection of cocaine exposure in the neonate. Analyses of urine, meconium, and amniotic fluid from mothers and infants exposed to cocaine.

Cocaine and its metabolites were measured in urine, meconium, and amniotic fluid specimens collected from 30 maternal-infant pairs with histories of prenatal cocaine use. Cocaine, benzoylecgonine, and ecgonine methyl ester were measured by isotope dilution gas chromatography-mass spectrometry. Mothers were interviewed at delivery regarding their cocaine use during pregnancy. There was qualitative agreement between the results of drug determinations in maternal urine, amniotic fluid, infant urine, and meconium. Although all of the mothers in this study admitted to using cocaine during their pregnancy, cocaine or its metabolites were detected only in the 20 cases in which cocaine was used within 3 weeks before delivery. We conclude that when sufficiently sensitive analytic methods are used, maternal urine, infant urine, and meconium analyses yield equivalent results for detection of prenatal cocaine exposure. Importantly, neither meconium nor urinary drug measurements detected cocaine exposure when the last reported use was prior to 3 weeks before delivery.

Multiple risk factors do not identify cocaine use in rural obstetrical patients.

This nonconcurrent, cohort study of consecutive admissions to one of three hospital units: labor and delivery (n = 474), well-born nursery (n = 100), and the neonatal intensive care unit (n = 100), was designed to determine the prevalence of cocaine exposure in a rural obstetrical sample and to determine the relationship between exposure and perinatal variables. Urines were analyzed for benzoylecgonine, and the Obstetrical Complications Scale was completed for each mother-infant pair. Elementary comparisons were made using chi 2 analyses and Student's t test. Stepwise discriminant and discriminant function analyses were performed. The prevalence of exposure in the three groups of subjects ranged from 5%-7%. No significant differences in perinatal variables were found between users and nonusers in either of the newborn samples. In the maternal sample the groups differed on twelve mother or infant factors. However, no single variable or set of variables predicted use versus nonuse in any of the groups.

Measurement of cocaine and metabolites in urine, meconium, and diapers by gas chromatography/mass spectrometry.

Analytical methods were evaluated for measuring cocaine (CO), benzoylecgonine (BE), and ecgonine methyl ester (EME) in urine and methanolic extracts from meconium and diapers by isotope dilution gas chromatography/mass spectrometry (GC/MS). Volatile derivatives of the extracted drugs were generated before GC/MS analysis. Methanolic extracts from meconium and diapers were reconstituted in drug-free urine and treated as above. The limit of detection for the GC/MS method was calculated to be approximately 11 ng per mL. Within-run coefficients of variation (CVs) for urinary CO, BE, and EME were 5.7, 5.3, and 11.4 percent, respectively (N = 10); corresponding CVs for meconium 6.4, 10.7, and 21.9 percent (N = 8). Quantitative results were linear from 25 to 10,000 ng per g of meconium and 25 to 5,000 ng per mL of urine. Day-to-day precision varied from eight percent (CV) for BE in refrigerated or frozen urine to 34 percent for EME in refrigerated meconium. Recoveries of CO, BE, and EME from urine were 63, 19, and 42 percent, respectively; corresponding recoveries from meconium were 64, 21, and 25 percent. Cocaine and metabolites were extracted from wet but meconium-free diapers into methanol, which was evaporated before reconstituting in drug-free urine and extraction on a solid phase column. The CO, BE, and EME were detected in previously drug-free meconium after portions were deposited in a diaper which was wet with drug-positive urine. Unless precautions are taken to prevent extracorporeal contamination of meconium with urine, concentrations of CO and metabolites in meconium may be substantially augmented by contamination with urine. Analysis by GC/MS of CO and metabolites extracted from diapers provides an attractive alternative to collection of urine, which is difficult and may cause discomfort for the neonate.