Cleaning of direct compression continuous manufacturing equipment through displacement of API residues by excipients.

This feasibility study evaluates a cleaning process designed to avoid the use of detergents and reduce operator exposure to the active pharmaceutical ingredient (API). The continuous manufacturing equipment was cleaned using excipients to displace ibuprofen residues from the system. The cleaning process was performed using 3.0 kg of Prosolv® and 3.0 kg of Tablettose® 70. The impact of different volumetric feed rates of the cleaning excipient was assessed. The displacement of API and blend residues was evaluated with in-line near infrared (NIR) spectroscopy. Principal component analysis (PCA) was performed to evaluate the cleaning progress as the Prosolv® flowed through the feeder, mixer and stream sampler. In-place Raman spectra were acquired from the material sticking to detect the ibuprofen residues. The study showed that Prosolv® and Tablettose® can remove ibuprofen residues effectively from the hopper, feeder screw, mixer paddles, shaft and stream sampler. The Process Analytical Technology (PAT) system can be utilized to detect API displacement during the cleaning process. However, dismantling and manual cleaning was required to remove material sticking at the surfaces adjacent to the rotating feeder screws and mixer paddles.

The Use of a Closed Feed Frame for the Development of Near-Infrared Spectroscopic Calibration Model to Determine Drug Concentration.

PURPOSE: This study evaluates the use of the closed feed frame as a material sparing approach to develop near-infrared (NIR) spectroscopic calibration models for monitoring blend uniformity. The effect of shear induced by recirculation on NIR spectra was also studied. METHODS: Calibration models were developed using NIR spectra obtained in the closed feed frame for two cases. For case 2, blends that flowed through the open feed frame were predicted with the model. The shear effect of the feed frame on the blends was assessed through the characterization of powder properties before and after recirculation. RESULTS: The physical characterization of the blends confirmed that the powder properties were not altered after recirculation within the closed feed frame. Both calibration models provided highly accurate predictions of the test sets with low bias (0.03% w/w and -0.06% w/w) and relative standard error of prediction (1.9% and 3.7%), respectively. The predictive performance of the calibration models was not affected by the shear effect. CONCLUSION: Recirculation within the closed feed frame did not change the physical properties of the blends studied. The prediction of blends flowing through the open feed frame was possible with a calibration model developed in the closed feed frame. The closed feed frame could reduce the materials needed to develop calibration models by more than 90%.

Assessment of blend uniformity in a stream sampler device using Raman spectroscopy.

This study describes the first implementation of Raman spectrometer in a stream sampler for the in-line monitoring of low drug concentration in poor flowability powder blends. Raman spectra were continuously acquired as the powder blends flowed through the stream sampler operating with a paddle wheel speed of 10 RPM and used to develop the calibration models. A calibration model was developed to quantify caffeine concentration from 1.50 to 4.50% w/w using Partial Least Squares Regression (PLS-R). Three test set blends were used to assess the prediction errors of the calibration model. Caffeine concentration was predicted for the test set blends with a root mean square error of prediction of 0.21% w/w and a low bias of -0.03% w/w. The calibration model showed good prediction performance with an estimated sample mass of 83 mg. Variographic analysis demonstrated the low process variance of the real-time spectral acquisition through minimum practical error and sill values. The results showed the ability of the Raman spectrometer coupled with the stream sampler to monitor low drug concentration for poor flowability blends.

Quantitative analysis of blend uniformity within a Three-Chamber feed frame using simultaneously Raman and Near-Infrared spectroscopy.

This study reports the use of Raman and Near-infrared (NIR) spectroscopy to simultaneously monitor the drug concentration in flowing powder blends within a three-chamber feed frame. The Raman probe was located at the top of the dosing chamber, while the NIR probe was located at the top of the filling chamber. The Raman and NIR spectra were continuously acquired while the powder blends flowed through the feed frame. Calibration models were developed with spectra from a total of five calibration blends ranging in caffeine concentration among 3.50 and 6.50% w/w. These models were optimized to predict three test set blends of 4.00, 5.00, and 6.00% w/w caffeine. The results showed a high predictive ability of the models based on root mean square error of predictions of 0.174 and 0.235% w/w for NIR and Raman spectroscopic models, respectively. Concentration profiles with higher variability were observed for the Raman spectroscopy predictions. An estimate of the mass analyzed by each spectrum showed that a NIR spectrum analyzes approximately 4.5 times the mass analyzed by a Raman spectrum; despite these differences in the mass analyzed, blend uniformity results are equivalent between techniques. Variographic analysis demonstrated that both techniques have significantly low sampling errors for the real-time monitoring process of drug concentration within the feed frame.

Monitoring of high-load dose formulations based on co-processed and non co-processed excipients.

This work presents the evaluation of a co-processed material for high-load dose formulations and its real-time monitoring by near-infrared (NIR) spectroscopy at the tablet press feed frame. The powder and tableting properties of co-processed material blends were evaluated and compared to the blend of the individual excipients. The formulations with the co-processed material showed excellent flow properties and were superior to the physical blend of individual excipients. Two NIR spectroscopic methods were developed to monitor ibuprofen concentration between 40.0 and 60.0% w/w, one method using a co-processed material as the main excipient and the other using the blend of the individual excipients. The NIR spectra were obtained while the powder blends flowed within a three-chamber feed frame from a Fette 3090 tablet press. The NIR spectroscopic method with the co-processed material presented better performance with significantly lower prediction error. Variographic analysis demonstrated that using the co-processed material considerably reduces the sampling and analytical errors in the in-line determination of ibuprofen. The authors understand that this is the first study where the sampling errors are evaluated as a function of the excipients used in the pharmaceutical formulation. This study demonstrated that selecting a suitable excipient for the formulation helps optimize the manufacturing process, reducing the magnitude of the total measurement error.

Utility of endoscopic ultrasound in idiopathic acute recurrent pancreatitis.

Idiopathic acute recurrent pancreatitis (IARP) is defined as at least two episodes of acute pancreatitis with the complete or near-complete resolution of symptoms and signs of pancreatitis between episodes, without an identified cause. There is a paucity of information about the usefulness of endoscopic ultrasound (EUS) in IARP. OBJECTIVES: To determine the diagnostic yield of EUS in IARP. DESIGN: A retrospective study was performed in patients with IARP evaluated by EUS between January 2009 and December 2016. Follow-up assessments of acute pancreatitis recurrence were carried out. RESULTS: Seventy-three patients with 102 EUS procedures were included. EUS was able to identify the cause of IARP in 55 patients (75.3%). The most common findings were chronic pancreatitis in 27 patients (49.1%), followed by lithiasic pathology in 24 patients (43.6%), and intraductal papillary mucinous neoplasm in four patients (7.3%). A directed treatment against EUS findings had a protective tendency associated with the final resolution of recurrence. There were no complications reported. CONCLUSION: EUS performed in patients with IARP helped to identify a possible cause in 2/3 of the cases. The majority of patients have a treatable disease.

An innovative sampling interface for monitoring flowing pharmaceutical powder mixtures.

A chute was designed following the principles of the Theory of Sampling to minimize the variations in powder flow and provide all particles in the flowing blends with the same opportunity of being selected as a sample. The design also reduces the thickness of the chute to allow the analysis of a higher portion of the flowing blends by a near infrared spectrometer. The blends that flowed through the chute had Carr's index values that fluctuated between 23 and 25 percent, indicating passable flowability. A powder fowling evaluation demonstrated that there was no powder accumulation at the inspection window of the chute. The mass flow rate profiles indicated that the system achieves mass steady-state in approximately 30 s and a throughput of 30 kg/h which makes it suitable for continuous manufacturing operations. An in-line NIR calibration model was developed to quantify caffeine concentrations between 1.51 and 4.52 % w/w. The spectra obtained from each experiment had minimal baseline variation. The developed NIR method was robust to throughput changes up to approximately ±7 %. The test blends in the caffeine concentration range between 2.02 % w/w and 4.02 % w/w met the dose uniformity requirements of the Ph.Eur. 9.0, chapter 2.9.47. Variographic analysis was done to estimate the analytical and sampling errors which yielded values below 0.01 (%w/w)2. The obtained results showed that this chute could also be used in a continuous manufacturing line or other applications with flowing powders.

Real-time quantification of low-dose cohesive formulations within a sampling interface for flowing powders.

This study investigates the performance of a sampling interface for monitoring cohesive, flowing powder formulations with Hausner's Ratio and Carr's Index higher than 1.5 and 35%, respectively. The sampler device was operated in combination with near-infrared (NIR) spectroscopy to quantify ibuprofen concentrations between 1.5 and 4.5% w/w. NIR spectra also provided essential information to study the process dynamics within the sampler. The 200 spectra per blend obtained demonstrated a continuous powder flow with no evidence of agglomerates or segregation within the sampler for a blend of 6 kg. A NIR calibration model was optimized to predict independent test blends, delivering root mean square error of predictions and bias under 0.1% w/w. The test blends were within specifications according to the requirements of European Pharmacopeia. Variographic analysis demonstrated that the sampler device may determine low drug concentration in cohesive powder blends, presenting sampling errors below 0.011 (%w/w)2. This analysis also demonstrated that an increase in the blend compressibility leads to a slight rise in sampling errors within the sampler device. The sampler device offers statistical robustness in the evaluation of blend uniformity, providing greater confidence in the quality determination of the cohesive powder blends without significantly affecting its flow properties.

In-line monitoring of low drug concentration of flowing powders in a new sampler device.

A novel sampler device for flowing powders was tested to quantify drug concentrations as low as 0.76% w/w in pharmaceutical powder blends. The sampler device was developed based on the powder flow behavior within a tablet press feed frame, following the principles laid down in the Theory of Sampling. Two Near-Infrared (NIR) spectroscopic calibration models were developed with powder blends that varied from 0.52 to 2.52% w/w and 1.51-4.52% w/w. The calibration models were able to determine caffeine concentration in test set blends with root mean square error of predictions and bias below 0.1% w/w. Samples were collected from the sampler device and analyzed by ultraviolet-visible (UV-Vis) to determine the caffeine concentration. A high agreement between the in-line NIR predictions and the sampled UV-Vis results was found. The paddle wheel speed in the sampler can be varied up to ±10% without affecting NIR predictions; however, the models did not respond adequately to a 25% increase in this speed. Variographic analysis showed that the sampler device may quantify low drug concentrations with nugget effects below 0.0050 (%w/w)2. This study demonstrate that the sampler device may handle throughputs up to 45 kg/h, without significantly affecting the physical properties of powder blends.

A sampling system for flowing powders based on the theory of sampling.

An innovative chute and stream sampler system for flowing powders has been developed and tested. The system is designed for representative sampling based on the principles of the Theory of Sampling (TOS). The sampling system was used in combination with near infrared (NIR) spectroscopy to determine the drug concentration of flowing powders. The system is comprised of three parts: a chute, a stream sampler and a sample collection port. The NIR spectra were obtained at the chute, before entering the sampler, and as the powder flowed through the stream sampler. Samples were also collected from the sample collection port to be analyzed using an ultraviolet-visible (UV-Vis) reference method to determine drug content. A total of eight pharmaceutical powder blends, ranging in concentration from 10.5(%w/w) to 19.5(%w/w) of caffeine, were used to test the sampling system. Materials were characterized before blends were made to provide information on flow properties. The throughput of the system was between 30 and 35 kg/h based on the flow properties of the blend. Drug concentration was effectively determined at the chute and stream sampler. The NIR calibration models showed low root mean squared errors of prediction, 0.65(%w/w) and 0.51(%w/w), for the chute and stream sampler respectively. The NIR calibration models also showed low bias values -0.36(%w/w) at the chute and 0.057(%w/w) at the stream sampler. Significant agreement was obtained between the results from the nondestructive NIR versus the destructive UV-Vis method. Variographic analysis was performed to estimate the analytical and sampling errors when determining the drug concentration at the chute and stream sampler respectively. The variographic analysis showed low analytical errors, 0.103(%w/w)2 and 0.181(%w/w)2 at the chute and stream sampler respectively. The analysis also showed that the minimum practical error (MPE) was around 0.2(%w/w)2 at both chute and stream sampler.

Características clínicas y microbiológicas de pacientes con neutropenia febril en un hospital Universitario / Clinical and microbiological characteristics of patients with febrile neutropenia in one Colombian Universitary Hospital

Objetivo: Describir las características clínicas, demográficas, frecuencia, tipo de aislamientos microbiológicos y resistencia a los antimicrobianos de pacientes con neoplasias hematológicas que presentaron como complicación neutropenia febril en el Hospital Universitario de San Ignacio Métodos: Estudio descriptivo observacional, se tomaron datos de historias clínicas de los pacientes adultos hospitalizados en la Unidad de Hematología y Trasplante de Médula Ósea, que cumplieron criterios de neutropenia febril entre enero de 2013 y diciembre de 2014 Resultados: se recolectaron 345 episodios de neutropenia febril, correspondientes a 193 pacientes. Se documentó foco infeccioso en el 68,1% de los episodios, con aislamiento microbiológico en el 62.9% de los episodios, con predominio de bacilos gram negativos, en 63,7% de los casos, seguido por los cocos gram positivos en 27,9% y hongos en 4,9%. En cuanto a los mecanismos de resistencia, en los aislamientos Escherichia coli y Klebsiella peumoniae se encontró producción de Beta Lactamasas de Espectro Extendido (BLEEs) en 17,5 y 13,8%; Carbapenemasas tipo KPC en 1,25 y 2,8% respectivamente. En cuanto a Staphylococcus aureus, se encontró resistencia a meticilina en 6,8% de los aislamientos. Mortalidad asociada a infección en 16,5% de los casos. Conclusión: En pacientes con Neoplasias Hematológicas con neutropenia febril post quimioterapia en el Hospital Universitario de San Ignacio encontramos alta probabilidad de documentación de foco infeccioso, con predominio de microorganismos gram negativos, especialmente enterobacterias; con comportamiento similar en pacientes post trasplante de precursores hematopoyéticos.

Objective: To describe the demographic and clinical characteristics, as well as frequency and type of bacterial isolate and resistance patterns in patients with hematological neoplasms complicated by febrile neutropenia at San Ignacio University Hospital Methods: This is a retrospective observational study. Data were collected from medical records of adult patients admitted in the Hemato-oncology and Bone Marrow Transplant Unit. Inclusion criteria was presence of febrile neutropenia in the setting of a hematological neoplasm from January 2013 to December 2014. Results: 345 episodes of febrile neutropenia from 193 patients were studied. An infectious focus was identified in 68.1% of episodes, and a bacterial isolate was obtained in 62.9% of episodes. The predominant microorganisms were gram-negative rods, gram-positive cocci, and fungi with a frequency of 63.7%, 27.9%, and 4.9% respectively. In term of resistance patterns, Escherichia coli and Klebsiella peumoniae isolates had a frequency of ESBL susceptibility pattern of 17.5% and 13.8% respectively; and a frequency of KPC susceptibility pattern of 1.25% and 2.8% respectively. The frequency of methicillin resistant Staphylococcus aureus was 6.8%. Death associated to infection ocurred in 16.5% of episodes. Conclusions: In patients with hematological neoplasms complicated by febrile neutropenia at San Ignacio University Hospital, we found a high rate of documentation of infectious focus, with a predominance of gram-negative rods, specially Enterobacteriacea; with a similar pattern in receptors of hematopoietic stem cell transplantation.

Feed frame: The last processing step before the tablet compaction in pharmaceutical manufacturing.

The feed frame is a force-feeding device used in the die filling process. The die filling process is crucial within pharmaceutical manufacturing to guarantee the critical quality attributes of the tablets. In recent years, interest in this unit has increased because it can affect the properties of the powder blend and tablets, and because of the success in real time monitoring of powder blend uniformity potential for Process Analytical Technology as described in this review. The review focuses on the recent advances in understanding the powder flow behavior inside the feed frame and how the residence time distribution of the powder within the feed frame is affected by the operating conditions and design parameters. Furthermore, this review also highlights the effect of the paddle wheel design and feed frame process parameters on the tablet weight, the principal variable for measuring die filling performance.

Cambios gasométricos en pacientes sometidos a resección prostática robótica / Gasometric changes in patients undergoing robotic prostatic resection

Resumen: Introducción: Las características propias de la cirugía robótica pueden tener efectos fisiológicos a nivel pulmonar que pueden producir complicaciones. Objetivo: Conocer los cambios gasométricos en pacientes sometidos a resección prostática robótica. Material y métodos: Treinta pacientes candidatos a resección prostática robótica fueron incluidos. Se midieron los tiempos quirúrgicos y parámetros de la gasometría arterial en cuatro tiempos: al momento de la inducción de la anestesia (T basal), 120 minutos posteriores a la insuflación de CO2 (T2h), a los 240 minutos (T4h) en la suspensión del capnoperitoneo (T final). Se realizó prueba de t de Student pareada para las variables con distribución normal, y la prueba U de Mann-Whitney en variables continuas no paramétricas, se consideró una significancia estadística de un valor de p ≤ 0.05. Resultados: La edad fue de 65.53 ± 5.92 años, la posición de Trendelenburg con inclinación < 30o se realizó en el 73.3%. El capnoperitoneo osciló de 10-25 mmHg, el tiempo quirúrgico fue de 326.7 ± 77.4 min. El aumento en promedio de la PaCO2 fue 8.57 mmHg: basal (31.33 ± 3.7 mmHg)- PaCO2 fin (39.9 ± 5 mmHg) p < 0.001. El pH disminuyó a partir de la segunda hora, en la medición final el 97% tenía valores < 7.35. Los valores del HCO3 tuvieron un descenso de -2.65 mEq/L: HCO3 basal (21.74 + 0.65 mEq/L)- HCO3 fin (19.09 + 0.78 mEq/L) p < 0.001. La presencia de acidemia se presentó en el 73.3%.

Abstract: Introduction: The characteristics of robotic surgery can have physiological effects at the pulmonary level that can produce complications. Objective: To know the gasometric changes in patients undergoing robotic prostatic resection. Material and methods: Thirty patients candidates for robotic prostatic resection were included. Surgical times and arterial blood gas parameters were measured at four times: at the time of induction of anesthesia (basal T), 120 minutes after CO2 insufflation (T2h), at 240 minutes (T.4h) in the capnoperitoneum suspension (final T). A paired Student's t-test was performed for the variables with normal distribution, and the Mann-Whitney U-test in nonparametric continuous variables was considered a statistical significance of a value of p ≤ 0.05. Results: The age was 65.53 ± 5.92 years, the position of Trendelenburg with inclination < 30o was made in 73.3%. The capnoperitoneum ranged from 10-25 mmHg, the surgical time was 326.7 ± 77.4 min. The average increase in PaCO2 was 8.57 mmHg: baseline (31.33 ± 3.7 mmHg) - PaCO2 end (39.9 ± 5 mmHg) p < 0.001. The pH decreased from the second hour on the final measurement 97% had values < 7.35. The values of HCO3 had a decrease of -2.65 mEq/L: basal HCO3 (21.74 + 0.65 mEq/L) - HCO3 end (19.09 + 0.78 mEq/L) p < 0.001. The presence of acidemia was presented in the 73.3%.

Assessment of blend uniformity in a continuous tablet manufacturing process.

Blend uniformity was monitored throughout a continuous manufacturing (CM) process by near infrared (NIR) spectroscopic measurements of flowing blends and compared to the drug concentration in the tablets. The NIR spectra were obtained through the chute after the blender and within the feed frame, while transmission spectra were obtained for the tablets. The CM process was performed with semi-fine acetaminophen blends at 10.0% (w/w). The blender was operated at 250 RPM, for best performance, and 106 and 495 rpm where a lower mixing efficiency was expected. The variation in blender RPM increased the variation in drug concentration at the chute but not at the feed frame. Statistical results show that the drug concentration of tablets can be predicted, with great accuracy, from blends within the feed frame. This study demonstrated a mixing effect within the feed frame, which contribute to a 60% decrease in the relative standard deviation of the drug concentration, when compared to the chute. Variographic analysis showed that the minimum sampling and analytical error was five times less in the feed frame than the chute. This study demonstrates that the feed frame is an ideal location for monitoring the drug concentration of powder blends for CM processes.

Stacked traits conferring multiple resistance to imazamox and glufosinate in soft wheat.

BACKGROUND: Conventional crossing of soft wheat cultivars resistant to imazamox and glufosinate resulted in two (Rados and Helter) lines resistant to both herbicides. Stacked traits conferring this dual herbicide resistance in these lines, compared with a susceptible (S) cultivar, were characterized. RESULTS: Rados and Helter lines were ∼ 18-fold more resistant (R) to glufosinate, and between 15.1 and 19.8-fold more resistant to imazamox than the S cultivar. Resistance to glufosinate and imazamox decreased up to 12% and 50%, respectively, when the herbicides were applied sequentially. The basal activities of the acetolactate and glutamine synthases were similar between R and S plants. Rados and Helter lines were 11.7- and 17.7-fold more resistant to imazamox than the S cultivar, due to the Ser653-Asn mutation in their imi-ALS genes. R lines, susceptible to glufosinate at the target site level, showed lower ammonia accumulation evidencing the activity of the phosphinothricin acetyl transferase. Absorption and translocation patterns for 14 C-imazamox and 14 C-glufosinate were similar between R and S cultivars and so do not contribute to resistance. CONCLUSION: Stacked traits conferring dual herbicide resistance to the lines Rados and Helter come from the resistant parents. These R lines are potential tools for weed management in wheat production, mainly via herbicide rotation. © 2018 Society of Chemical Industry.

Development of near infrared spectroscopic calibration models for in-line determination of low drug concentration, bulk density, and relative specific void volume within a feed frame.

This study describes the development of a near infrared (NIR) calibration model for real time determination of drug concentration, powder density, and porosity or relative specific void volume (RSVV) of 3.00%w/w acetaminophen blends within a feed frame. The NIR calibration model was developed from 1.50 to 4.50%w/w of acetaminophen, using a high variability of major excipients (from 12.92 to 81.95%w/w) which facilitates the prediction of powder density and RSVV based on near infrared calibration spectra. The model using second derivative as spectral preprocessing explained the changes related to acetaminophen concentration in the first latent variable. The second latent variable was related to changes in concentration of microcrystalline cellulose and lactose in the powder blends. NIR calibrations were also developed based on the bulk density and RSVV of the powder blends using the same design as the API model, due to the physical properties of the particles and their effects on the NIR spectra. The RSVV was predicted for the independent set blends with an RSEP(%) below 4% with a significantly low bias (0.04 cm3/g) from reference values of 1.33 to 1.58 cm3/g. The bulk density model also exhibited excellent predictions with RSEP(%) below 2.6% and significantly low bias (0.01 g/cm3) from reference values of 0.45 to 0.51 g/cm3. The excellent results obtained show the potential of near infrared spectroscopic measurements within the feed frame for a Process Analytical Technology method to control the critical properties such as tablet mass, hardness and dissolution in batch and continuous manufacturing processes.

In line monitoring of the powder flow behavior and drug content in a Fette 3090 feed frame at different operating conditions using Near Infrared spectroscopy.

Near infrared (NIR) spectroscopy was used to determine the drug concentration in 3% (w/w) acetaminophen blends within the complex flow regime of the tablet press feed frame just before tablet compaction. NIR spectra also provided valuable information on the powder flow behavior within the feed frame and were used to track when a process enters or leaves the steady state. A partial least squares regression calibration model was developed with powder mixtures that varied from 1.5 to 4.5% (w/w) by obtaining 135 spectra after steady state for each concentration while the feed frame and die disc operated at 30.5 revolutions per minute (rpm). The calibration model determined drug concentration in validation blends with a root mean square error of prediction and bias below 0.1% (w/w). The robustness of the NIR calibration model was evaluated by determining the effect of variation on the operating conditions (paddle wheel speed and die disc speed) on NIR predictions. This work found that the paddle wheel speed can be increased up to 30% and the die disc speed decrease 10% without affecting NIR predictions. The results demonstrated that paddle wheel speed has a significant effect on the wave powder behavior (frequency and amplitude) but does not have significant effect on the mass hold-up within feed frame. The die disc speed does not affect wave powder behavior but affects significantly the mass hold-up inside the feed frame. This information can be used to reduce the tablet weight variability and ensure that this critical attribute is met.

Candidiasis sistémica en pacientes críticos, factores predictores de riesgo / Systemic candidiasis in critical patients: risk predictors

Candida sp. constituye el microorganismo más frecuentemente implicado en las infecciones por hongos en pacientes críticamente enfermos. La candidemia es la forma más común de candidiasis invasiva, ingresando al torrente sanguíneo por el tracto gastrointestinal y la piel. A nivel mundial la candidemia se destaca como una de las principales causas de morbilidad con aumentos significativos en la incidencia y prevalencia en los últimos años. Además, eleva los costos de la atención hospitalaria. Aunque diversos estudios demuestran que el inicio temprano del tratamiento antifúngico mejora el pronóstico de los pacientes, se tienen dificultades con las pruebas diagnósticas existentes, debido a que no tienen un nivel adecuado de sensibilidad y un óptimo rendimiento. Por tal razón, en la actualidad se vienen utilizando diversos índices clínicos predictores de candidiasis invasiva como Ostrosky, Candida Score, Escala de Pittet, entre otros, los cuales tienen un alto valor predictivo negativo que permite reconocer los pacientes que no se benefician de un inicio temprano de un tratamiento antifúngico mientras se confirma el diagnóstico por laboratorio. La terapia antifúngica disponible para el tratamiento de las candidemias en UCI está compuesta básicamente por tres grupos de medicamentos, los azoles, los polienos y las equinocandinas. A pesar de la validación de los índices predictores de candidiasis invasiva en otros países, se desconoce cuál de estos sería el más efectivo para predecir esta patología en la región

Candida sp. is the microorganism most frequently involved in fungal infections in critically ill patients. Candidemia is the most common form of invasive candidiasis entering the bloodstream from the gastrointestinal tract and skin. Worldwide candidemia stands out as one of the leading causes of morbidity with significant increases in its incidence and prevalence in recent years. In addition, it raises the costs of hospital care. Although several studies show that early initiation of antifungal treatment improves patients' prognosis, there are difficulties with existing diagnostic tests, because they do not have an adequate level of sensitivity and optimum performance. For this reason, various clinical indices are currently being used as predictors of invasive candidiasis, such as Ostrosky Candida Score, Candida Score, Pittet Candida Colonization Index, among others, which have a high negative predictive value that allows to recognize patients who do not benefit from an early initiation of an antifungal treatment while the diagnosis is confirmed by laboratory. Antifungal therapy available for the treatment of candidemia in the ICU consists basically of three groups of drugs: azoles, polyenes and echinocandins. Despite the validation of predictors of invasive candidiasis in other countries, it is still unknown which of these would be the most effective for predicting this disease in the region

Multiple mechanisms are involved in new imazamox-resistant varieties of durum and soft wheat.

Weed control in wheat is one of the major goals of farmers in their efforts toward obtaining the highest crop yields for human foods. Several studies (dose-response, enzyme activity, absorption-translocation and metabolism) were conducted to characterize the resistance level of two new wheat cultivars called Rafalín (Triticum aestivum) and Antoñín (T. durum) that were obtained by conventional breeding based on Clearfield® technology; they are resistant (R) to imazamox compared to their sensitive (S) counterparts (Gazul and Simeto, respectively). The R-cultivars were 93.7-fold (Rafalín) and 43.7-fold (Antoñín) more resistant than their respective S-cultivars. The acetolactate synthase (ALS) enzyme activity revealed high resistance to imidazolinone (IMI) herbicides in R-cultivars, but no cross-resistance to other ALS herbicides was found. The Ser653Asn mutation that confers resistance to IMI herbicides was identified in the imi1 and imi2 genes of Rafalín and only in the imi1 gene of Antoñín. The 14C-imazamox absorption did not differ between the R- and S-cultivars. Imazamox was metabolized by Cyt-P450 into imazamox-hydroxyl and imazamox-glucoside in the R-cultivars, altering their translocation patterns. The differential sensitivity to imazamox between R-cultivars was due to the number of resistance genes that carry each genotype. The R-cultivars Rafalín and Antoñín could be excellent weed control tools.

Distribución estacional de miasis mucocutánea. Nuestra experiencia / Seasonal distribution of mucocutaneousmyiasis. Our experience / Distribuição sazonal de miíase mucocutânea. A nossa experiencia

Introducción: la miasis es una lesión producida por larvas de mosca que infestan animales, de cuyos tejidos se alimentan en forma parasitaria. En nuestro servicio de otorrinolaringología tratamos frecuentemente pacientes con miasis mucocutáneas. El comprender la distribución estacional de esta patología podría ser una herramienta útil para la prevención de la misma. Métodos: Se valoraron las historias clínicas informatizadas del servicio de Otorrinolaringología del Hospital Federico Abete de Malvinas Argentinas, entre enero de 2013 y diciembre de 2015, utilizando como filtro la palabra “miasis”; de las cuales se analizaron las variables: mes de infestación, sitio anatómico comprometido, la edad, el género y la temperatura al momento de la consulta. Resultados: Se encontraron 27 pacientes. La edad promedio fue de 42 años. Quince pacientes masculinos y 12 femeninos. Sitio anatómico comprometido: conducto auditivo externo: 11; traqueostoma: 8; Sitio operatorio: 5; oído medio: 3. Todos fueron diagnosticados en las estaciones más cálidas. Conclusiones: Se observó la aparición de miasis en las estaciones más cálidas. Sería aconsejable tomar mayor cantidad de medidas preventivas durante estas épocas del año, para evitar los casos de infestación larvaria, cuando es posible.

Introduction: Myiasis refers to the damage caused by fly larvaes, which infest animals, including humans, and who feed in form parasitic of their dead or living tissue, causing tissue destruction. In our department of otolaryngology, we often treat patients with mucocutaneous myiasis. Understand the seasonal distribution of this disease could be a useful tool for preventing it. Method: Computerized medical records of Otolaryngology Service of Hospital Municipal Dr. Federico Abete of Malvinas Argentinas were valued, in the period between 2013 and 2015, it was used as a filter the word “myiasis”. Were found a series of 27 cases with diagnosis of mucocutaneous myiasis; of which were analyzed the variables: month of infestation, involved anatomic site, age and temperature at the time of medical consultation. Results: 27 patients were found. The average age was 42 years. 15 male patients and 12 female patients. Involved anatomic site: external auditory canal: 11; tracheostomy: 8; infestation surgical site: 5; middle ear: 3. All were diagnosed in the warmer seasons. Conclusions: The appearance of myiasis was observed in the warmer seasons. It would be advisable to take as many preventative measures during these times of the year to avoid cases of larval infestation, when possible.

Introdução: Miíase é uma lesão causada por larvas de moscas que infestam animais e dos que se alimentam de forma parasitária de seus tecidos. Em nosso departamento de otorrinolaringología tratamos muitas vezes pacientes com miíase mucocutânea. Compreender a distribuiçãos a zonal destado ença poderia ser uma ferramenta útil para evitar isso. Método: Forama valiados registros médicos computadorizados de Serviço de Otorrinolaringologia do Hospital Municipal Dr. Federico Abete de Malvinas Argentinas, no período entre 2013 e 2015, ele foi usado como filtro a palavra “miasis”. Foram encontradas uma série de 27 casos com diagnóstico de miíase mucocutânea; dos quais foram analisados as variáveis: mês de infestação, local anatómico en volvidos, idade e sexo dos pacientes; que foram comparados com os dados de temperatura do Servicio Meteorológico Nacional. Resultados: 27 pacientes foram encontrados. A idade média foi de 42 anos. 15 pacientes do sexo masculino e 12 do sexo feminino. Local anatômico envolvidos: canal auditivo externo: 11; traqueostomia: 8; infestação de sítio cirúrgico: 5; ouvido médio: 3. Todos foram diagnosticados nas estações mais quentes. Conclusões: O aparecimento de miíases foi observada nas estações mais quentes. Seria aconselhável tomar tantas medidas preventivas durante estas épocas do ano para evitar casos de infestação larval, quando possível.