Cholelithiasis and associated complications in pediatric patients. / Colelitiasis y complicaciones asociadas en pacientes pediátricos.

OBJECTIVE: To review the clinical characteristics and complications associated with cholelithiasis in pediatric patients by identifying risk factors and assessing surgical management and results. METHODS: Retrospective study in patients under 18 years of age undergoing cholelithiasis surgery. The following data were analyzed: age, sex, body mass index (BMI), associated comorbidities, clinical presentation, symptom duration, surgical treatment, pathological report, postoperative complications, and hospital stay. RESULTS: 135 cholelithiasis patients underwent surgery from 2013 to 2018, with an increasing trend in the annual number of cholecystectomies. Most patients were adolescents (86.7%) and female (72.6%), and they had cholesterol gallstones (86.6%) and >85 BMI (33%). Mean symptom duration was 85 days (SD: 148). Symptomatic cholelithiasis was present in 131 cases (97%). CL associated complications were recorded in 64.4% of patients, with cholecystitis, pancreatitis, and choledocholithiasis being the most frequent ones. All patients underwent laparoscopic cholecystectomy; 4 (2.9%) required conversion to open surgery, and 6 (4.4%) had postoperative complications. Mean hospital stay and postoperative follow-up were 5.7 days (SD: 4) and 2.3 months (SD: 1.9), respectively. CONCLUSIONS: Non-hemolytic cholelithiasis in the pediatric population is more frequent in female overweight and obese adolescents. Symptomatic cholelithiasis is associated with higher risk of complications such as cholecystitis, pancreatitis, or choledocholithiasis, which supports early surgical management.

OBJETIVO: Revisión de las características clínicas y complicaciones asociadas de los pacientes pediátricos con colelitiasis, mediante la identificación de factores de riesgo, la evaluación del manejo quirúrgico y sus resultados. METODOS: Estudio retrospectivo en pacientes menores de 18 años, intervenidos quirúrgicamente por colelitiasis. Se analizaron datos como edad, género, índice de masa corporal (IMC), comorbilidades asociadas, presentación clínica, tiempo de los síntomas, tratamiento quirúrgico, reporte de patología, complicaciones posoperatorias y estancia hospitalaria. RESULTADOS: Se intervinieron quirúrgicamente 135 pacientes con colelitiasis entre los años 2013 a 2018, con una tendencia ascendente en el número de colecistectomías realizadas anualmente. La mayoría fueron pacientes adolescentes (86,7%), con cálculos de colesterol (86,6%), de género femenino (72,6%) y con IMC > 85 (33%). El tiempo de los síntomas en promedio fue de 85 días (DE 148). Colelitiasis sintomática se presentó en 131 casos (97%). Complicaciones asociadas a CL se registraron en 64,4% pacientes, siendo las más frecuentes colecistitis, pancreatitis y coledocolitiasis. En todos los pacientes se realizó colecistectomía laparoscópica, 4 (2,9%) requirieron conversión a cirugía abierta y 6 (4,4%) presentaron complicaciones postoperatorias. La estancia hospitalaria y el seguimiento posoperatorio fueron en promedio 5,7 días (DE 4) y 2,3 meses (DE 1,9), respectivamentea. CONCLUSIONES: La colelitiasis no hemolítica en la población pediátrica, es más frecuente en pacientes adolescentes de género femenino con sobrepeso u obesidad. La colelitiasis sintomática está asociada con mayor riesgo de complicaciones como colecistitis, pancreatitis o coledocolitiasis, en consecuencia, se justifica una intervención quirúrgica temprana.

Effect of length of time post-mortem on quality and freezing capacity of Cantabric chamois (Rupicapra pyrenaica parva) epididymal spermatozoa.

Genome Resource Banks are keystones in the ex-situ conservation of wild species. Post-mortem (PM) collection of epididymal spermatozoa is an opportunistic and valuable source of germplasm, the time from the death of the animal limits its use. Seeking to improve germplasm preservation strategies for the chamois (Rupicapra sp.), the effect of PM time on epididymal sperm quality and freezability was studied using the Cantabrian chamois. Samples were classified according to PM collection time, up to 216 h (refrigerated), and cryopreserved (Tris-citric acid-fructose, 430 mOsm/kg, 15% egg yolk, 8% glycerol; freezing at -20 °C/min). Sperm quality was assessed after recovery and post-thawing (motility by CASA, HOS test, abnormal forms, cytoplasmic droplets, and viability and acrosomal damage by flow cytometry). The sperm mass pH and osmolality showed a positive correlation with time. Total sperm motility dropped after 2 days PM, with progressivity and sperm velocities remained similar up to 3 days PM. Sperm freezability was acceptable, with the post-thawing HOST, motility, progressivity, VAP, VCL, VSL and BCF negatively correlating with PM time. Overall, chamois epidydimal samples were not adequate for preservation after 6 days PM. Freezability capacity could make these spermatozoa suitable for specific ART even if kept refrigerated for several days PM.

[Diagnosis and management in pediatric patients with ovarian masses]. / Diagnóstico y manejo de masas ováricas en pacientes pediátricas.

OBJECTIVE: Review of the diagnosis and management of ovarian masses in children, through the identification of preoperative risk factors of malignancy, the evaluation of surgical management and its results. METHODS: Retrospective study in pediatric patients under 18 years old, managed surgically by ovarian masses. Analyzed data were symptoms, imagining, tumor markers, treatment, outcomes and pathology. The primary endpoint was ovarian malignancy. RESULTS: We identified 54 patients with ovarian masses between 2014 and 2017, of which 49 were benign and 5 malignant; The malignant ovarian masses were significantly larger than the benign, with an average of 19.4 cm vs 6.49 cm (p = 0.0001); had greater solid component in the imaging and positive tumor markers (p = 0.001) and were treated with oophorectomy plus tumor staging surgery. Forty-three patients with benign tumors underwent ovarian preservation surgery. The postoperative follow-up of all the patients was on average 3.4 months (1-25 months) and 20.3% presented pelvic pain associated with alterations of the menstrual cycle in their postoperative control. There are no reports of recurrence or contralateral ovarian tumor. CONCLUSIONS: Large masses with solid components and positive tumor markers were significant predictors of malignancy. Minimally invasive ovarian preserving surgery should be considered as the first treatment option in masses with low risk of malignancy. On the other hand, oophorectomy plus tumor staging surgery should be considered for ovarian tumors with a high risk of malignancy.

OBJETIVO: Revisión del diagnóstico y manejo de las masas ováricas en población infantil, mediante la identificación de factores de riesgo preoperatorios de malignidad, la evaluación del manejo quirúrgico y sus resultados. METODOS: Estudio retrospectivo en pacientes pediátricas menores de 18 años, intervenidas quirúrgicamente por masas ováricas. Se analizaron datos como síntomas, imágenes diagnósticas, marcadores tumorales, tratamiento, resultados y patología. La variable principal fue malignidad ovárica. RESULTADOS: Se identificaron 54 pacientes con masas ováricas entre el año 2014 a 2017, de las cuales 49 fueron benignas y 5 malignas. Las masas ováricas malignas fueron significativamente más grandes que las benignas, con media de 19,4 cm vs 6,49 cm (p = 0,0001); tuvieron mayor componente sólido en los hallazgos imagenológicos y marcadores tumorales positivos (p = 0,001) y fueron tratadas con ooforectomía más cirugía de estadificación tumoral. A 43 pacientes con tumores benignos se les realizó cirugía preservadora de ovario. El seguimiento postoperatorio de todas las pacientes fue en promedio de 3,4 meses (1-25 meses) y el 20,3% presentaron dolor pélvico asociado a alteraciones del ciclo menstrual en su control postoperatorio. No hay reportes de recidiva ni tumor de ovario contralateral. CONCLUSIONES: Masas grandes, con componentes sólidos y marcadores tumorales positivos fueron predictores significativos de malignidad. La cirugía preservadora de ovario por vía mínimamente invasiva debe ser considerada como primera opción de tratamiento en masas con bajo riesgo de malignidad; Por otra parte, la ooforectomía más cirugía de estadificación tumoral, debe ser considerada para los tumores ováricos con alto riesgo de malignidad.

Analysis of seminal plasma from brown bear (Ursus arctos) during the breeding season: Its relationship with testosterone levels.

Seminal plasma (SP) plays an important role in the motility, viability and maintenance of the fertilizing capacity of mammalian spermatozoa. This study is the first on brown bear (Ursus arctos) SP components, and has two main objectives: 1) to define the SP composition in bear ejaculate and 2) to identify variations in SP composition in relation to high and low levels of testosterone in serum during the breeding season. Forty-eight sperm samples from 30 sexually mature male brown bears (Ursus arctos) were obtained by electroejaculation, and their serum testosterone levels were assessed to sort the animals into 2 groups (high and low testosterone levels, threshold 5 ng/dl). The biochemical and protein compositions of the SP samples were assessed, and sperm motility was analyzed. We found that lactate dehydrogenase was significantly higher in the low-serum-testosterone samples, while concentrations of lipase and Mg+ values were significantly higher in the high-serum-testosterone samples. In contrast, sperm motility did not significantly differ (P>0.05) between the testosterone level groups (total motility: 74.42.8% in the high-level group vs. 77.1±4.7% in the low-level group). A reference digital model was constructed since there is no information for this wild species. To do this, all gel images were added in a binary multidimensional image and thirty-three spots were identified as the most-repeated spots. An analysis of these proteins was done by qualitative equivalency (isoelectric point and molecular weight) with published data for a bull. SP protein composition was compared between bears with high and low serum testosterone, and three proteins (binder of sperm and two enzymes not identified in the reference bull) showed significant (P<0.05) quantitative differences. We conclude that male bears with high or low serum testosterone levels differs only in some properties of their SP, differences in enzyme LDIP2, energy source LACT2, one protein (similar to BSP1) and Mg ion were identified between these two groups. These data may inform the application of SP to improve bear semen extenders.

Improving sperm banking efficiency in endangered species through the use of a sperm selection method in brown bear (Ursus arctos) thawed sperm.

BACKGROUND: Sperm selection methods such as Single Layer Centrifugation (SLC) have been demonstrated to be a useful tool to improve the quality of sperm samples and therefore to increase the efficiency of other artificial reproductive techniques in several species. This procedure could help to improve the quality of genetic resource banks, which is essential for endangered species. In contrast, these sperm selection methods are optimized and focused on farm animals, where the recovery task is not as important as in endangered species because of their higher sperm availability. The aim of this study was to evaluate two centrifugation methods (300 x g/20 min and 600 x g/10 min) and three concentrations of SLC media (Androcoll-Bear -80, 65 and 50%) to optimise the procedure in order to recover as many sperm with the highest quality as possible. Sperm morphology could be important in the hydrodynamic relationship between the cell and centrifugation medium and thus the effect of sperm head morphometry on sperm yield and its hydrodynamic relationship were studied. RESULTS: The samples selected with Androcoll-Bear 65% showed a very good yield (53.1 ± 2.9) although the yield from Androcoll-Bear 80% was lower (19.3 ± 3.3). The latter showed higher values of motility than the control immediately after post-thawing selection. However, both concentrations of colloid (65 and 80%) showed higher values of viable sperm and viable sperm with intact acrosome than the control. After an incubation of 2 h at 37 °C, the samples from Androcoll-Bear 80% had higher kinematics and proportion of viable sperm with intact acrosome. In the morphometric analysis, the sperm selected by the Androcoll-Bear 80% showed a head with a bigger area which was more elongated than the sperm from other treatments. CONCLUSIONS: We conclude that sperm selection with Androcoll-Bear at either 65% or 80% is a suitable technique that allows a sperm population with better quality than the initial sample to be obtained. We recommend the use of Androcoll-Bear 65% since the yield is better than Androcoll-Bear 80%. Our findings pave the way for further research on application of sperm selection techniques to sperm banking in the brown bear.

Pain in the ICU - The fifth sign, not the fifth element / Dolor en la UCI: el quinto signo, no el quinto elemento

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Impact of harmful use of alcohol on the sedation of critical patients on mechanical ventilation: A multicentre prospective, observational study in 8 Spanish intensive care units / Impacto del consumo de riesgo de alcohol en la sedación de pacientes críticos en ventilación mecánica: Estudio observacional prospectivo, multicéntrico en 8 unidades de cuidados intensivos (UCI) Españolas

PURPOSE: To evaluate the impact of a history of harmful use of alcohol (HUA) on sedoanalgesia practices and outcomes in patients on mechanical ventilation (MV). METHODS: A prospective, observational multicentre study was made of all adults consecutively admitted during 30 days to 8 Spanish ICUs. Patients on MV > 24 h were followed-up on until discharge from the ICU or death. Data on HUA, smoking, the use of illegal (IP) and medically prescribed psychotropics (MPP), sedoanalgesia practices and their related complications (sedative failure [SF] and sedative withdrawal [SW]), as well as outcome, were prospectively recorded. RESULTS: A total of 23.4% (119/509) of the admitted patients received MV >24h; 68.9% were males; age 57.0 (17.9) years; APACHE II score 18.8 (7.2); with a medical cause of admission in 53.9%. Half of them consumed at least one psychotropic agent (smoking 27.7%, HUA 25.2%; MPP 9.2%; and IP 7.6%). HUA patients more frequently required PS (86.7% vs. 64%; p < 0.02) and the use of >2 sedatives (56.7% vs. 28.1%; p < 0.02). HUA was associated to an eightfold (p < 0.001) and fourfold (p < 0.02) increase in SF and SW, respectively. In turn, the duration of MV and the stay in the ICU was increased by 151h (p < 0.02) and 4.4 days (p < 0.02), respectively, when compared with the non-HUA group. No differences were found in terms of mortality. CONCLUSIONS: HUA may be associated to a higher risk of SF and WS, and can prolong MV and the duration of stay in the ICU in critical patients. Early identification could allow the implementation of specific sedation strategies aimed at preventing these complications

OBJETIVO: Evaluar el impacto del consumo enólico de riesgo (HUA) en las prácticas de sedoanalgesia y la evolución de pacientes en ventilación mecánica (MV). MÉTODOS: Estudio prospectivo observacional multicéntrico de todos los adultos ingresados consecutivamente durante 30 días en 8 UCIs españolas. Los pacientes en MV > 24h fueron evaluados hasta el alta de UCI o exitus. Se registró el HUA, consumo de tabaco, psicótropos ilegales (IP) o bajo prescripción médica (MPP) las prácticas de sedoanalgesia y sus complicaciones asociadas (Fracaso de Sedación/SF y Síndrome de Privación/SW) así como datos sobre la evolución clínica. Resultados: El 23.4% (119/509) de los ingresados, requirieron VM ≥ 24 h: Varones 68.9%; Edad 57.0 (17.9) años; APACHEII 18.8 (7.2); Ingreso por causa medica 53.9%. La mitad consumían al menos un psicotrópico (tabaco: 27.7%; HUA: 25.2%; PPM: 9.2%; PI: 7.6%). Los pacientes con HUA requirieron más frecuentemente PS (86.7% vs. 64%; p < 0.02) y doble sedación (56.7% vs. 28.1%; p < 0.02). El HUA se asoció a incidencias 8 (p < 0.001) y 4 (p < 0.02) veces superiores de SF y SW y prolongó en 151 (p < 0.02) horas y 4.4 (p < 0.02) días, el tiempo de VM y estancia media en UCI respectivamente respecto al grupo no-HUA. No se encontraron diferencias en la mortalidad. Conclusiones: El HUA podría asociarse a un mayor riesgo de SF y WS y prolongar los tiempos de MV y LOS en los pacientes críticos. Su identificación precoz permitiría implementar estrategias específicas de sedación orientadas a prevenir estas complicaciones

Impact of harmful use of alcohol on the sedation of critical patients on mechanical ventilation: A multicentre prospective, observational study in 8 Spanish intensive care units.

PURPOSE: To evaluate the impact of a history of harmful use of alcohol (HUA) on sedoanalgesia practices and outcomes in patients on mechanical ventilation (MV). METHODS: A prospective, observational multicentre study was made of all adults consecutively admitted during 30 days to 8 Spanish ICUs. Patients on MV >24h were followed-up on until discharge from the ICU or death. Data on HUA, smoking, the use of illegal (IP) and medically prescribed psychotropics (MPP), sedoanalgesia practices and their related complications (sedative failure [SF] and sedative withdrawal [SW]), as well as outcome, were prospectively recorded. RESULTS: A total of 23.4% (119/509) of the admitted patients received MV >24h; 68.9% were males; age 57.0 (17.9) years; APACHE II score 18.8 (7.2); with a medical cause of admission in 53.9%. Half of them consumed at least one psychotropic agent (smoking 27.7%, HUA 25.2%; MPP 9.2%; and IP 7.6%). HUA patients more frequently required PS (86.7% vs. 64%; p<0.02) and the use of >2 sedatives (56.7% vs. 28.1%; p<0.02). HUA was associated to an eightfold (p<0.001) and fourfold (p<0.02) increase in SF and SW, respectively. In turn, the duration of MV and the stay in the ICU was increased by 151h (p<0.02) and 4.4 days (p<0.02), respectively, when compared with the non-HUA group. No differences were found in terms of mortality. CONCLUSIONS: HUA may be associated to a higher risk of SF and WS, and can prolong MV and the duration of stay in the ICU in critical patients. Early identification could allow the implementation of specific sedation strategies aimed at preventing these complications.

Dolor y miedo en la UCI / Pain and fear in the ICU

Dolor y miedo siguen siendo de los recuerdos más frecuentes que refieren los pacientes tras su ingreso en UCI. Recientemente una importante política calificó la UCI como la sucursal del infierno. Es necesario llevar a cabo cambios profundos en cuanto a la relación directa con los pacientes y sus familias, así como cambios en el diseño ambiental y en la organización del trabajo y de las visitas, para desterrar la visión que tiene nuestra sociedad acerca de la UCI. En una etapa donde se aboga sobre la movilización precoz del paciente crítico se hace necesario mejorar las estrategias de analgesia y sedación. La UCI es el lugar más adecuado para administrar y monitorizar el efecto de cualquier analgésico. La correcta analgesia no debe ser una asignatura pendiente del intensivista sino una asignatura de obligado cumplimiento

Pain and fear are still the most common memories that refer patients after ICU admission. Recently an important politician named the UCI as the branch of the hell. It is necessary to carry out profound changes in terms of direct relationships with patients and their relatives, as well as changes in environmental design and work and visit organization, to banish the vision that our society about the UCI. In a step which advocates for early mobilization of critical patients is necessary to improve analgesia and sedation strategies. The ICU is the best place for administering and monitoring analgesic drugs. The correct analgesia should not be a pending matter of the intensivist but a mandatory course

On the prediction of Hodgkin lymphoma treatment response

Purpose. The cure rate in Hodgkin lymphoma is high, but the response along with treatment is still unpredictable and highly variable among patients. Detecting those patients who do not respond to treatment at early stages could bring improvements in their treatment. This research tries to identify the main biological prognostic variables currently gathered at diagnosis and design a simple machine learning methodology to help physicians improve the treatment response assessment. Methods. We carried out a retrospective analysis of the response to treatment of a cohort of 263 Caucasians who were diagnosed with Hodgkin lymphoma in Asturias (Spain). For that purpose, we used a list of 35 clinical and biological variables that are currently measured at diagnosis before any treatment begins. To establish the list of most discriminatory prognostic variables for treatment response, we designed a machine learning approach based on two different feature selection methods (Fisher’s ratio and maximum percentile distance) and backwards recursive feature elimination using a nearest-neighbor classifier (k-NN). The weights of the k-NN classifier were optimized using different terms of the confusion matrix (true- and false-positive rates) to minimize risk in the decisions. Results and conclusions. We found that the optimum strategy to predict treatment response in Hodgkin lymphoma consists in solving two different binary classification problems, discriminating first if the patient is in progressive disease; if not, then discerning among complete and partial remission. Serum ferritin turned to be the most discriminatory variable in predicting treatment response, followed by alanine aminotransferase and alkaline phosphatase. The importance of these prognostic variables suggests a close relationship between inflammation, iron overload, liver damage and the extension of the disease (AU)

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[Pain and fear in the ICU]. / Dolor y miedo en la UCI.

Pain and fear are still the most common memories that refer patients after ICU admission. Recently an important politician named the UCI as the branch of the hell. It is necessary to carry out profound changes in terms of direct relationships with patients and their relatives, as well as changes in environmental design and work and visit organization, to banish the vision that our society about the UCI. In a step which advocates for early mobilization of critical patients is necessary to improve analgesia and sedation strategies. The ICU is the best place for administering and monitoring analgesic drugs. The correct analgesia should not be a pending matter of the intensivist but a mandatory course.

La actividad citotóxica de las células natural killer como herramienta diagnóstica en pacientes pediátricos críticos con sospecha de síndrome hemofagocítico / Natural killer cell cytotoxic activity in critical pediatric patients with suspected hemophagocytic syndrome

OBJETIVO: Determinar el papel de la citotoxicidad de las células natural killer (NK) en pacientes pediátricos críticos con sospecha de síndrome hemofagocítico (SH). DISEÑO: Estudio prospectivo realizado en el período comprendido entre septiembre de 2008 y febrero de 2014. ÁMBITO: Se ha realizado en el Laboratorio de Onco-Hematología del Hospital Infantil Universitario Niño Jesús de Madrid. PACIENTES: Se analizaron 30 muestras de sangre periférica de pacientes ingresados en la Unidad de Cuidados Intensivos de diferentes centros hospitalarios. Los pacientes, 18 niños y 12 niñas, tenían una media de edad de 4,7 años (rango 0,2-22). La citotoxicidad NK se comparó con un control sano del mismo sexo y similar edad. INTERVENCIÓN: Determinamos la citotoxicidad in vitro NK frente a la línea celular K562 mediante fluorescencia resuelta en el tiempo (Europium-TDA) en condiciones de reposo, tras estimulación con interleucina 15 y bloqueo con el anticuerpo Fas ligando. VARIABLE DE INTERÉS: La citotoxicidad NK. RESULTADOS: En 20 pacientes la citotoxicidad NK estaba disminuida (p = 0,001). De ellos, 9 fueron diagnosticados de SH primario y 11 de SH secundario. En 10 pacientes la citotoxicidad fue normal; ninguno fue diagnosticado de SH. La estimulación con interleucina 15 aumentó la citotoxicidad NK en los SH secundarios, y el bloqueo de Fas ligando la disminuyó en los pacientes con SH primarios (p = 0,001). CONCLUSIONES: En nuestra experiencia, la citotoxicidad NK constituye una prueba útil para el diagnóstico de los SH. La estimulación con interleucina 15 y el bloqueo con Fas ligando nos pueden ayudar al diagnóstico diferencial de los SH primarios y secundarios

AIM: To determine the role of natural killer (NK) cytotoxic activity in patients with suspected hemophagocytic lymphohistiocytosis syndrome (HLH). DESIGN: A prospective study was conducted from September 2008 to February 2014. SCOPE: The study was carried out in the Hematological Oncology Laboratory of Hospital Infantil Universitario Niño Jesús, Madrid (Spain). PATIENTS: We analyzed 30 peripheral blood samples from intensive care patients with suspected HLH. There were 18 males and 12 females, with a mean age of 4.7 years (range 0.2-22). NK cell cytotoxicity was compared with healthy controls according to age and sex. INTERVENTION: In vitro NK cell cytotoxicity against the K562 cell line was determined by time-resolved fluorescence (Europium-TDA) under resting conditions, after interleukin 15 stimulation, and following block with Fas ligand antibody. VARIABLE OF INTEREST: NK cell cytotoxicity. RESULTS: A total of 20 patients showed a significant decrease of NK cell activity compared with controls (P=.001). Nine of these patients were diagnosed with primary HLH. A total of 10 patients were diagnosed with secondary HLH. Cytotoxic activity was normal in 10 subjects. None of them were diagnosed with HLH. Interleukin 15 stimulation increased NK cell cytotoxicity in secondary HLH, and blocking Fas ligand on NK cells decreased cytotoxic activity in primary HLH patients (P = .001). CONCLUSIONS: In our experience, NK cell cytotoxic activity measured by time-resolved fluorescence is a simple and useful clinical diagnostic test for HLH. Interleukin 15 stimulation and Fas ligand blocking on NK cells could help differentiate between primary and secondary HLH

On the prediction of Hodgkin lymphoma treatment response.

PURPOSE: The cure rate in Hodgkin lymphoma is high, but the response along with treatment is still unpredictable and highly variable among patients. Detecting those patients who do not respond to treatment at early stages could bring improvements in their treatment. This research tries to identify the main biological prognostic variables currently gathered at diagnosis and design a simple machine learning methodology to help physicians improve the treatment response assessment. METHODS: We carried out a retrospective analysis of the response to treatment of a cohort of 263 Caucasians who were diagnosed with Hodgkin lymphoma in Asturias (Spain). For that purpose, we used a list of 35 clinical and biological variables that are currently measured at diagnosis before any treatment begins. To establish the list of most discriminatory prognostic variables for treatment response, we designed a machine learning approach based on two different feature selection methods (Fisher's ratio and maximum percentile distance) and backwards recursive feature elimination using a nearest-neighbor classifier (k-NN). The weights of the k-NN classifier were optimized using different terms of the confusion matrix (true- and false-positive rates) to minimize risk in the decisions. RESULTS AND CONCLUSIONS: We found that the optimum strategy to predict treatment response in Hodgkin lymphoma consists in solving two different binary classification problems, discriminating first if the patient is in progressive disease; if not, then discerning among complete and partial remission. Serum ferritin turned to be the most discriminatory variable in predicting treatment response, followed by alanine aminotransferase and alkaline phosphatase. The importance of these prognostic variables suggests a close relationship between inflammation, iron overload, liver damage and the extension of the disease.

Succinil-colina. ¿Hasta cuándo? / Succinylcholine. Until when?

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[Natural killer cell cytotoxic activity in critical pediatric patients with suspected hemophagocytic syndrome]. / La actividad citotóxica de las células natural killer como herramienta diagnóstica en pacientes pediátricos críticos con sospecha de síndrome hemofagocítico.

AIM: To determine the role of natural killer (NK) cytotoxic activity in patients with suspected hemophagocytic lymphohistiocytosis syndrome (HLH). DESIGN: A prospective study was conducted from September 2008 to February 2014. SCOPE: The study was carried out in the Hematological Oncology Laboratory of Hospital Infantil Universitario Niño Jesús, Madrid (Spain). PATIENTS: We analyzed 30 peripheral blood samples from intensive care patients with suspected HLH. There were 18 males and 12 females, with a mean age of 4.7 years (range 0.2-22). NK cell cytotoxicity was compared with healthy controls according to age and sex. INTERVENTION: In vitro NK cell cytotoxicity against the K562 cell line was determined by time-resolved fluorescence (Europium-TDA) under resting conditions, after interleukin 15 stimulation, and following block with Fas ligand antibody. VARIABLE OF INTEREST: NK cell cytotoxicity. RESULTS: A total of 20 patients showed a significant decrease of NK cell activity compared with controls (P=.001). Nine of these patients were diagnosed with primary HLH. A total of 10 patients were diagnosed with secondary HLH. Cytotoxic activity was normal in 10 subjects. None of them were diagnosed with HLH. Interleukin 15 stimulation increased NK cell cytotoxicity in secondary HLH, and blocking Fas ligand on NK cells decreased cytotoxic activity in primary HLH patients (P=.001). CONCLUSIONS: In our experience, NK cell cytotoxic activity measured by time-resolved fluorescence is a simple and useful clinical diagnostic test for HLH. Interleukin 15 stimulation and Fas ligand blocking on NK cells could help differentiate between primary and secondary HLH.

Alternative procedures for the cryopreservation of brown bear ejaculates depending on the flexibility of the "in cooling" period (5°C).

The adaptability of cryopreservation protocols for brown bear spermatozoa collected under field conditions and frozen in a nearby laboratory (transported for a few hours) or shipped to a reference laboratory for sex sorting (transported for a few days) was evaluated. Forty-nine electroejaculates from 15 mature brown bears were extended to 100×10(6) sperm/mL in a TES-Tris-Fructose based extender and cryopreserved (-20°C/min to -100°C and stored at -196°C). After thawing, the quality of the seminal samples was assessed for total (TM), progressive (PM) motility and kinetic parameters - by CASA -, and viability (VIAB), viable and non-apoptotic status (YOPRO-), high membrane mitochondrial potential (MIT) and intact acrosomes (iACR) - by flow cytometry -. In Experiment 1, we assessed different storage times (0, 0.5, 1 - control -, 4-5, 7-8 and 11-12 h) at 5°C from final dilution to freezing. After thawing, non-equilibrated samples (0 h) showed lower values of iACR, TM and PM. No significant differences were found for the different periods of equilibration tested. In Experiment 2, we evaluated three long-term storage times (24, 48 and 72 h) at 5°C before freezing using storage for 1h as control. The post-thawing quality of brown bear spermatozoa declined markedly after 48-72 h of pre-freezing. In conclusion, our findings suggest the possibility of extending the pre-freezing cooling period up to 24h post-collection without freezing. This knowledge should enable the adaptation of the freezing protocols for when a special handling conditions are required such as the shipment of seminal samples to technological centers for the pre-freezing application of enhancer spermatic biotechnologies.

Salvaging urospermic ejaculates from brown bear (Ursus arctos).

The objective of this study was to reverse the osmotic stress of sperm in urine contaminated bear ejaculates that were obtained by electroejaculation using pre-freezing washing or density gradient centrifugation isolation. In Experiment 1, ejaculates were divided into six aliquots, five were diluted in each washing extender: 200, 300, 400, 500 and 700 mOsm/kg (prepared from a Tes-Tris-Fructose base, adding water or fructose as corresponds), at a 1:2 ratio (raw semen: washing solution, v/v); and the other aliquot was handled without washing (Control group). Samples were centrifuged at 600 × g for 6 min prior to freezing. In Experiment 2, ejaculates were divided into two aliquots: one was diluted 1:1 with TCG (Tris-Citric acid-Glucose) and centrifuged at 600 × g for 6 min (Centrifugation Control; C-Control); the other was treated with PureSperm density gradient column. After treatments, samples were cryopreserved. Sperm motility, viability (SYBR-14/propidium iodide (PI)) and acrosomal status (peanut agglutinin-fluorescein isothiocyanate (PNA-FITC)/PI) were analyzed before and after freezing. Ejaculates with an initial osmolality of less than 120 mOsm/kg treated with pre-freezing washing, and the Control sample had greater pre-freezing sperm motility than the raw ejaculate, but sperm viability was not different among these groups. The samples washed with 700 mOsm/kg solutions had the least pre-freezing viability. In the post-thawing evaluation, pre-freezing washing treatments did not provide any improvement in comparison with the Control sample, and treatment with 700 mOsm/kg extender had deleterious effects in all urospermic samples. PureSperm density gradient centrifugation applied to urospermic raw semen was suitable for improving sperm motility and viability of pre-freezing samples and the selected spermatozoa had greater freezing capacity.

Bendamustine as salvage treatment for patients with relapsed or refractory mantle cell lymphoma patients: a retrospective study of the Spanish experience.

Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1-8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3-18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1-54.2). Median overall survival (OS) was 30 months (95 % CI 25.6-34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses (p < 0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses (p < 0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL.