Prediction of massive bleeding. Shock index and modified shock index. / Predicción de hemorragia masiva. Índice de shock e índice de shock modificado.

OBJECTIVE: To determine the predictive value of the Shock Index and Modified Shock Index in patients with massive bleeding due to severe trauma. DESIGN: Retrospective cohort. SETTING: Severe trauma patient's initial attention at the intensive care unit of a tertiary hospital. SUBJECTS: Patients older than 14 years that were admitted to the hospital with severe trauma (Injury Severity Score >15) form January 2014 to December 2015. VARIABLES: We studied the sensitivity (Se), specificity (Sp), positive and negative predictive value (PV+ and PV-), positive and negative likelihood ratio (LR+ and LR-), ROC curves (Receiver Operating Characteristics) and the area under the same (AUROC) for prediction of massive hemorrhage. RESULTS: 287 patients were included, 76.31% (219) were male, mean age was 43,36 (±17.71) years and ISS was 26 (interquartile range [IQR]: 21-34). The overall frequency of massive bleeding was 8.71% (25). For Shock Index: AUROC was 0.89 (95% confidence intervals [CI] 0.84 to 0.94), with an optimal cutoff at 1.11, Se was 91.3% (95% CI: 73.2 to 97.58) and Sp was 79.69% (95% CI: 74.34 to 84.16). For the Modified Shock Index: AUROC was 0.90 (95% CI: 0.86 to 0.95), with an optimal cutoff at 1.46, Se was 95.65% (95% CI: 79.01 to 99.23) and Sp was 75.78% (95% CI: 70.18 to 80.62). CONCLUSION: Shock Index and Modified Shock Index are good predictors of massive bleeding and could be easily incorporated to the initial workup of patients with severe trauma.

Utility of the central venous-to-arterial CO2 difference to predict adverse outcomes after liver transplantation.

OBJECTIVE: Test whether the development of abnormal venous-to arterial CO2 difference (ΔPCO2) during the early phases of postoperative care after a liver transplantation (LT) is related to multi-organ dysfunction and outcomes. MATERIALS AND METHODS: Prospective cohort study accomplished in a mixed intensive care unit (ICU) at a university hospital. We included 150 eligible patients after a LT between 2015 and 2018. Patients were classified in four predefined groups according to the ΔPCO2 evolution during the first 6 h of resuscitation: (1) persistently normal ΔPCO2 (normal at T0 and T6); (2) decreasing ΔPCO2 (high at T0, normal at T6); (3) increasing ΔPCO2 (normal at T0, high at T6); and (4) persistently high ΔPCO2 (high at T0 and T6). Multiorgan dysfunction at day-3 was compared for predefined groups and a Kaplan Meier curve was constructed to show the survival probabilities using a log-rank test to evaluate differences between groups. A Spearman-Rho was used to test the agreement between cardiac output and ΔPCO2. RESULTS: There were no significant differences between the study groups regarding higher SOFA scores at day-3 (P = .86), Δ-SOFA (P = .088), as well as global mortality rates (χ²â€¯= 5.72; P = .126) and mortality rates at day-30 (χ²â€¯= 2.23; P = .5252). A significantly poor inverse agreement between cardiac output and ΔPCO2 was observed (r2 -0,17; P = ,002) at different points of resuscitation. CONCLUSIONS: After a LT, central venous-to-arterial CO2 difference was not associated with survival or postoperative adverse outcomes in a critical care patients population.

Fanconi-like anemia related to a FANCM mutation.

Fanconi anemia is primarily inherited as an autosomal recessive genetic disorder with common delays in diagnosis and challenging treatments. Fanconi anemia patients have a high risk of developing solid tumors, particularly in the head and neck or anogenital regions. The diagnosis of Fanconi anemia is primarily based on the chromosomal breakage but FA gene sequencing is recommended in all patients with a positive chromosome fragility test. Here, we present a 32-year-old man with advanced tonsil squamous cell carcinoma and fatal toxicity after the first cycle of chemotherapy. No anemia was present. A recent variant mutation if the FANCM gene was detected (c1511_1515delGAGTA (pArg504AsnfsTer29)). Homozygous or double heterozygous pathogenic variants have been reported in FANCM and linked to azoospermia and primary ovarian failure without anemia. Alterations in this gene have also been associated with a genetic predisposition for solid tumors (breast and ovarian cancer) and hematological malignancies (B-cell acute lymphoblastic leukemia). Due to the hypersensitivity of these patients to DNA-damaging agents such as chemotherapy and radiotherapy, surgery is the best treatment option for malignant solid tumors. Dose reductions or alternative regimens of chemotherapy and/or radiotherapy are recommended in FA patients who develop a malignant tumor.

Cavernomas in children with brain tumors: a late complication of radiotherapy.

BACKGROUND: Delayed complications of radiation therapy comprise cerebral atrophy, radionecrosis and induction of tumors. Recent reports indicate the possibility of the "de-novo" formation of intracranial cavernomas in patients submitted to radiation therapy to the brain. OBJECTIVES: To report three children, two with medulloblastomas and one with a pineal germinoma, treated with radiotherapy that developed intracerebral cavernous hemangiomas some years after treatment. With this work, we aim to draw attention to this occurrence in the neurosurgical community. RESULTS: The patients were two girls and one boy with ages comprised between 2.5 and 7 years (mean 5.2 years). The average interval from irradiation to the appearance of cavernoma was of 5.3 years (range 5-6 years). The lesions were found during the routine neuroimaging studies performed for the follow-up of their primary neoplasms. No patient showed signs or symptoms related to the cavernomas. However, the three children will need both clinical and neuroimaging surveillance to monitor the evolution of these incidentally discovered lesions. CONCLUSIONS: Intracranial cavernomas can occur years after cerebral radiation therapy. In spite of previous reports that show a high incidence of bleeding lesions, cavernomas may be found incidentally during the neuroimaging surveillance studies that are performed to children with brain tumors previously treated with radiotherapy. In these cases, a conservative attitude seems to be advisable, reserving surgery only for those lesions that grow or bleed.

H-ras immunohistochemical expression and molecular analysis of urinary bladder lesions in grazing adult cattle exposed to bracken fern.

Chronic ingestion of bracken fern (Pteridium spp.) by cattle produces upper alimentary tract and urinary bladder tumours causing a syndrome called bovine enzootic haematuria (BEH). Previous studies demonstrated ptaquiloside-DNA adducts and mutations in the h-ras gene in ileal epithelial cells of bracken fern-fed calves. Systematic inspection of the bladder mucosa of grazing cattle (n=126) from bracken-fern areas was carried out in a slaughterhouse. Of the 126 slaughterhouse cattle, 46 showed macroscopical lesions of the bladder. These bladders, together with six others known to have BEH, were examined histopathologically and by H-ras immunohistochemistry. Thirteen affected bladders were also examined by H-ras molecular analysis to detect mutations. Macroscopical and histological study of urinary bladder lesions found at the slaughterhouse revealed chronic cystitis (34.1%) and tumours (2.4%). There was significantly increased immunohistochemical expression of H-ras (P<0.05) in chronic cystitis (H-ras=53.24%) and bladder tumours (H-ras=63.60%) as compared with normal urinary bladders (H-ras=4.32%). A silent mutation (D38D) was detected in one animal with a mixed bladder tumour. The prevalence of urinary bladder lesions (chronic cystitis and tumours) obtained at the slaughterhouse was higher than expected. This study demonstrates that close inspection of urinary bladders of adult grazing cows is necessary to prevent possible human exposure to bracken-fern carcinogens. The absence of mutations in the codons of h-ras studied did not exclude the presence of polymorphisms in other regions of the gene (promoter or regulation sequences) or in other genes (belonging or not to the ras family) that significantly affect the H-ras protein.

Impact of changes in the treatment of nasopharyngeal carcinoma: an experience of 30 years.

Two hundred and twenty-eight patients with nasopharyngeal carcinoma were treated in a single institution in a 31-year period. Overall survival (OS), disease-free survival (DFS), and complete response (CR) rates were analyzed. In addition, survival and control rates from 1960 to 1975 and from 1976 to 1991 were evaluated. In the latter group, a comparative study was performed between patients treated with neoadjuvant chemotherapy (NCT) before radiotherapy (RT) (45) and patients treated with radiotherapy alone (45). OS at 5 and 10 years were 42 and 34%, and DFS rates were 35 and 30%, respectively. CR was achieved in 184 patients (81%). Tumor progression and survival were strongly associated with T-category. Use of fashioned blocks, age and T-category were the most important factors influencing survival in a multivariate analysis. In the patients treated with NCT, rates of CR and OS were not significantly different when compared with the concurrent RT alone group. Ninety-nine patients had recurrence (54%) and 58 received rescue treatment. Modern radiotherapy techniques have greatly assisted in the improvement of tumor control rates. Chemotherapy must be further evaluated and new treatments for relapsed patients are needed.

Comparison of aceclofenac with piroxicam in the treatment of osteoarthritis.

A multicentre, double-blind, randomised, parallel group study was undertaken to investigate the efficacy and safety of aceclofenac (123 patients, 100 mg twice daily) in comparison to piroxicam (117 patients, 20 mg once daily and placebo once daily) in patients with osteoarthritis of the knee. The treatment period of two months was preceded by a washout period of one week duration. On completion of the study, patients in both aceclofenac and piroxicam-treated groups exhibited significant improvement in pain intensity and functional capacity of the affected knee, as represented by the Osteoarthritis Severity Index (OSI) (p < 0.0001 and p < 0.001 respectively). This was further substantiated following the patient's assessment of pain intensity using the Visual Analogue Scale (VAS), in which significant improvements were demonstrated at all time points for each treatment group (p < 0.001). Although both treatment groups showed a significant improvement in all investigator's clinical assessments (functional exploration of the knee, knee flexion and extension (EXT)), there were no significant differences between the groups. There was, however, a more rapid improvement in knee flexion in the aceclofenac group after 15 days of treatment. Both aceclofenac and piroxicam were well tolerated by patients, the most commonly reported adverse events being gastrointestinal, although their incidence was low. Only 24 patients on aceclofenac, as opposed to 33 on piroxicam complained of dyspepsia, epigastralgia and pyrosis. While 7 patients in each group were withdrawn because of adverse events, only one patient with piroxicam was withdrawn because of severe upper gastrointestinal bleeding. Twice as many reports of fecal blood loss were made in the piroxicam group in comparison to the aceclofenac group. In summary, this study confirms the therapeutic efficacy of aceclofenac and suggests that it is a well-tolerated alternative NSAID to piroxicam in the treatment of osteoarthritis.

Diversity of temporal self-organized behaviors in a biochemical system.

The numerical study of a glycolytic model formed by a system of three delay-differential equations revealed a notable richness of temporal structures which included the three main routes to chaos, as well as a multiplicity of stable coexisting states. The Feigenbaum, intermitency and quasiperiodicity routes to chaos can emerge in the biochemical oscillator. Moreover, different types of birhythmicity, trirhythmicity and hard excitation emerge in the phase space. For a single range of the control parameter it can be observed the coexistence of two quasiperiodicity routes to chaos, the coexistence of a stable steady state with a stable torus, and the coexistence of a strange attractor with different stable regimes such as chaos with different periodic regimes, chaos with bursting behavior, and chaos with torus. In most of the numerical studies, the biochemical oscillator has been considered under periodic input flux being the mean input flux rate 6 mM/h. On the other hand, several investigators have observed quasiperiodic time patterns and chaotic oscillations by monitoring the fluorescence of NADH in glycolyzing yeast under sinusoidal glucose input flux. Our numerical results match well with these experimental studies.

Dynamic behavior in glycolytic oscillations with phase shifts.

Practically all of the studies of glycolytic oscillations in homogeneous spatial mediums have been performed through the construction of systems of ordinary differential equations and the search for their solutions. In this kind of modelling, the system dynamic behavior is considered to depend only on the values adopted by the parameters related to the dependent variables. In the present work, the modeling of a biochemical system through a system of functional differential equations with delay allows us to analyse the consequences that the variations in the parametric values linked to the independent variable (time) have upon the integral solutions of the system. In our model, the delays correspond with phase shifts in the initial functions for two dependent variables. The results of our researches show that when a instability-generating multienzymatic mechanism suffers variations of the delay time in any of its variables, a wide range of different dynamic responses can be produced. Our work is presented as an enlargement on the dynamic study of biochemical oscillations in general and, particularly, the glycolytic oscillations, under the consideration of the existence of variations in the phase shifts during the oscillations of metabolites involved in the studied reactive processes.

Intermittency route to chaos in a biochemical system.

The numerical analysis of a glycolytic model performed through the construction of a system of three differential-delay equations reveals a phenomenon of intermittency route to chaos. In our biochemical system, the consideration of delay time variations under constant input flux as well as frequency variations of the periodic substrate input flux allows us, in both cases, to observe a type of transition to chaos different from the 'Feigenbaum route'.

[First results of the IOBA low vision unit]. / Primeros resultados de la Unidad de Baja Visión del IOBA.

PURPOSE: To verify the efficacy a treatment for the rehabilitation of vision in our Unit for Clinical Low Vision in the testing of improvements in patient's efficiency for daily life activities. MATERIAL AND METHOD: 80 patients were studied. Ophthalmologic and optometric evaluation followed by a customised vision rehabilitation program were performed according to patient's immediate needs. In a second stage a telephoned questionnaire was filled in order to record efficacy of prescribed visual aids in their own environment. RESULTS: Rehabilitation training resulted in 89% of patients showing improvement in their quality of life in both fields; functional and psychological. 85% of patients showed improvement in near activities and 35% in far activities. DISCUSSION: A correct and specialised low vision refraction and a posterior vision rehabilitation training in the use of optical and non optical aids show increase in quality of life in patients with severe visual deficiencies.

[Functional improvement after vision rehabilitation in low monocular vision after myopic macular degeneration and retinal detachment]. / Mejora funcional tras la rehabilitación visual en una paciente con visión monocular deficitaria debido a degeneración macular miópica y desprendimiento de retina.

PURPOSE: We present a case of a 62 year-old woman, with a single eye functional vision (VA of 0.16) who improved her vision after following a vision rehabilitation program, which included optical and non-optical devices for daily performance. CONCLUSIONS: A correct optometric evaluation and a training program are key factors to improve quality of life in low vision patients, whose ocular pathology allows no other treatment.

Multiple comparison procedures for simple one-way ANOVA with dependent data.

The independence assumption, although reasonable when examining cross-sectional data using single-factor experimental designs, is seldom verified by investigators. A Monte Carlo type simulation experiment was designed to examine the relationship between true Types I and II error probabilities in six multiple comparison procedures. Various aspects, such as patterns of means, types of hypotheses, and degree of dependence of the observations, were taken into account. Results show that, if independence is violated, none of the procedures control a using the error rate per comparison. At the same time, as the correlation increases, so does the per-comparison power.

Estudio de riesgo de recurrencia de trastorno del espectro autista (TEA) en hermanos de niños con diagnóstico TEA / Study on recurrence risk of autism spectrum disorders (ASD) in siblings of children diagnosed with ASD

El trastorno del espectro autista (TEA) es un trastorno del desarrollo, común de la niñez, con una fuerte predisposición genética y alta heredabilidad. El riesgo de recurrencia en hermanos oscila entre 10-20% y en caso de familias con dos o más niños afectados el riesgo de recurrencia aumenta hasta un 35%. Dentro de las pruebas complementarias para el diagnóstico, el gold standard es la escala ADOS, existe además una prueba de pesquisa, el M-CHAT. Objetivo: evaluar riesgo de recurrencia de TEA en hermanos menores de niños con diagnóstico de TEA. Materiales y Métodos: se realizó un estudio de tipo transversal, observacional y descriptivo. Fueron estudiados niños entre 18-36 meses, hermanos de pacientes con diagnóstico de TEA. La evaluación del desarrollo se realizó utilizando: Escalas CAT/CLAMS, M-CHAT y ADOS 2. Resultados: se estudiaron 39 hermanos. 25 fueron varones y 14 fueron mujeres. Se identificaron 5 niños con diagnóstico de TEA, por lo que el riesgo de recurrencia en la población estudiada fue de 13%, con una relación varón/mujer de 4/1. Del resto de la población estudiada, 13% reunieron criterios para fenotipo ampliado del autismo (Broader Autism Phenotype ­BAP­ en su sigla en inglés), 31% presentaron retraso del lenguaje(RL) y 7%retraso global del desarrollo (RGD). Solo el 36% presentó desarrollo típico. Conclusión: Los hermanos de niños afectados representan un grupo de riesgo para problemas del desarrollo, que debe ser tenido en cuenta por los profesionales de la salud que siguen longitudinalmente a niños con diagnóstico confirmado de TEA (AU)

Autism spectrum disorder (ASD) is a developmental disorder that is common in childhood with a strong genetic predisposition and high heritability. The risk of recurrence in siblings is found to be between 10-20% and in families with two or more affected children recurrence risk is as high as 35%. Among the complementary diagnostic tests, the gold standard is the ADOS scale, and additionally the M-CHAT screening test. Objective: To evaluate the recurrence risk of ASD in younger siblings of children diagnosed with ASD. Material and Methods: A cross-sectional, observational, descriptive study was conducted. Children between 18- 36 months of age, siblings of children diagnosed with ASD were studied. Development was assessed using the CAT/CLAMS, MCHAT, and ADOS 2 scales. Results: 39 siblings were studied; 25 were male and 14 female. Five children with ASD were identified, accounting for a recurrence risk of 13% in the study population and a male/female ratio of 4/1. Of the remaining children, 13% met the criteria for the broader autism phenotype (BAP), 31% had language delay (LD), and 7% global developmental delay (GDD). Only 36% had normal development. Conclusion: Siblings of affected children are at risk for developmental disorders that should be taken into account by health professionals that ongitudinally follow children with a confirmed diagnosis of ASD (AU)

Mutation status and immunoglobulin gene rearrangements in patients from northwest and central region of Spain with chronic lymphocytic leukemia.

The aim of this study was to investigate the frequency and mutation status of the immunoglobulin heavy variable chain (IGHV) in a cohort of 224 patients from northwest and central region of Spain diagnosed with chronic lymphocytic leukemia (CLL), and to correlate it with cytogenetic abnormalities, overall survival (OS) and time to first treatment (TTFT). 125 patients had mutated IGHV, while 99 had unmutated IGHV. The most frequently used IGHV family was IGHV3, followed by IGHV1 and IGHV4. The regions IGHV3-30, IGHV1-69, IGHV3-23, and IGHV4-34 were the most commonly used. Only 3.1% of the patients belonged to the subfamily IGHV3-21 and we failed to demonstrate a worse clinical outcome in this subgroup. The IGHV4 family appeared more frequently with mutated pattern, similar to IGHV3-23 and IGHV3-74. By contrast, IGHV1-69 was expressed at a higher frequency in unmutated CLL patients. All the cases from IGHV3-11 and almost all from IGHV5-51 subfamily belonged to the group of unmutated CLL.

A method for obtaining Schwann cell cultures from adult rabbit nerve based on "in vitro" pre-degeneration and neuregulin treatment.

Schwann cells (SCs) are basic elements for cell therapy and tissue engineering in the central and peripheral nervous system. Therefore, the development of a reliable method to obtain SC cultures is required. For possible therapeutic applications the cultures need to produce a sufficiently large number of SCs with a high level of purity in a relatively short period of time. To increase SC yield and purity we pre-degenerated pieces of 1-2 mm of adult rabbit sciatic nerves by incubating them for seven days in Dulbecco's Modified Eagle's Medium supplemented with 10% fetal bovine serum, penicillin/streptomycin and NRG1-ß1. Following pre-degeneration the nerve pieces were dissociated and then cultured for 6 or 15 days in the same culture medium. After 6 days of culture we obtained around 9.5x10³ cells/mg with approximately 94% SCs (S-100 positive) purity. After 15 days of culture the yield was about 80x10³ cells/mg and the purity was approximately 75%. Pre-degeneration and subsequent culture of small pieces of adult nerve with NRG1-ß1 supplemented medium increased the number of SCs and restricted the overgrowth of fibroblast-like cells.

Absence of relevant effects of 5 mT static magnetic field on morphology, orientation and growth of a rat Schwann cell line in culture.

The aim of this study is to observe possible changes in the morphology, orientation or cell growth of an in vitro cultured Schwann cell line by 24 h exposure to 5 mT static magnetic fields. The magnetic field generator basically consists of a pair of circular coils in a Helmholtz arrangement and enables temperature to be controlled (37+/-0.1 degrees C). We did not find any statistically significant differences in the cell growth rate between control and exposed cells, nor did we observe any differences in cell morphology or orientation.