Antitumoral effect of maintained neutrophilia induced by rhG-CSF in a murine model of pancreatic cancer.

Although the protumoral functions of polymorphonuclear neutrophils are well known, some now-forgotten studies report antitumoral roles for these cells. The present work examines the antitumoral effect of maintained neutrophilia induced via the injection of recombinant human granulocyte colony stimulating factor (rhG-CSF, 100 µg/kg/day) in a Panc-1 subcutaneous xenograft murine model of pancreatic cancer. This treatment was compared with gemcitabine administration (120 mg/kg every two days) and a saline control (n = 6-7 mice per group). Compared to the controls, both the rhG-CSF- and gemcitabine-treated mice showed significantly suppressed tumor growth by day 4 (p < 0.001 and p = 0.013 respectively). From a mean starting volume of 106.9 ± 3.1 mm3 for all treatment groups, the final mean tumor volumes reached were 282.0 ± 30.7 mm3 for the rhG-CSF-treated mice, 202.6 ± 18.1 mm3 for the gemcitabine-treated mice and 519.4 ± 62.9 mm3 for the control mice (p < 0.004 and p < 0.01, respectively, vs. control). The rhG-CSF-treated tumors showed higher percentage necrosis than those treated with gemcitabine (37.4 ± 4.6 vs. 7.5 ± 3.0; p < 0.001). This is the first report of a clear anti-tumoral effect of rhG-CSF when used in monotherapy against pancreatic cancer. Since rhG-CSF administration is known to be associated with very few adverse events, it may offer an attractive alternative in the clinical treatment of pancreatic cancer.

Analysing the concept of diagnostic inertia in hypertension: a cross-sectional study.

AIMS: The aim of this study was to quantify diagnostic inertia (DI) when the physician fails to diagnose hypertension and determine its associated factors. METHODS: This cross-sectional, observational study involved all patients without a diagnosis of hypertension who had their blood pressure (BP) measured at least three times during the second half of 2010 (N = 48,605). Patients with altered mean BP figures (≥ 140/90 mmHg) were considered to experience DI. Secondary variables: gender, atrial fibrillation, diabetes mellitus, dyslipidemia, cardiovascular disease, age and the physician having attended a cardiovascular training course (ESCARVAL). Associated factors were assessed by multivariate logistic regression analysis. RESULTS: Diagnostic inertia was present in 6450 patients (13.3%, 95% CI: 13.0-13.6%). Factors significantly associated with DI were: male gender (OR = 1.46, 95% CI: 1.37-1.55, p < 0.001), atrial fibrillation (OR = 0.73, 95% CI: 0.58-0.92, p = 0.007), the ESCARVAL cardiovascular course (OR = 0.88, 95% CI: 0.81-0.96, p = 0.005), diabetes mellitus (OR = 0.93, 95% CI: 0.87-0.99, p = 0.016), cardiovascular disease (OR = 0.77, 95% CI: 0.67-0.88, p < 0.001) and older age (years) (18-44→OR = 1; 45-59→OR = 12.45, 95% CI: 11.11-13.94; 60-74→OR = 18.11, 95% CI: 16.30-20.12; ≥ 75→OR = 20.43, 95% CI: 18.34-22.75; p < 0.001). The multivariate model had an area under the ROC curve of 0.81 (95% CI: 0.80-0.81, p < 0.001). CONCLUSIONS: This study will help clinical researchers differentiate between the two forms of DI (interpretation of a positive screening test and interpretation of positive diagnostic criteria). The results found here in patients with hypertension suggest that this problem is prevalent, and that a set of associated factors can explain the outcome well (AUC>0.80).

Differences in the management of hypertension, diabetes mellitus and dyslipidemia between obesity classes.

We did not find any paper that assessed clinical inertia in obese patients. Therefore, no paper has compared the clinical inertia rates between morbidly and nonmorbidly obese patients. A cross-sectional observational study was carried out. We analysed 8687 obese patients ⩾40 years of age who attended their health-care center for a checkup as part of a preventive program. The outcome was morbid obesity. Secondary variables were as follows: failure in the management of high blood pressure (HBP), high blood cholesterol (HBC) and high fasting blood glucose (HFBG); gender; personal history of hypertension, dyslipidemia, diabetes, smoking and cardiovascular disease; and age (years). We analysed the association between failures and morbid obesity by calculating the adjusted odds ratio (OR). Of 8687 obese patients, 421 had morbid obesity (4.8%, 95% confidence interval (CI): 4.4-5.3%). The prevalence rates for failures were as follows: HBP, 34.7%; HBC, 35.2%; and HFBG, 12.4%. Associated factors with morbid obesity related with failures were as follows: failure in the management of HBP (OR=1.42, 95% CI: 1.15-1.74, P=0.001); failure in the management of HBC (OR=0.73, 95% CI: 0.58-0.91, P=0.004); and failure in the management of HFBG (OR=2.24, 95% CI: 1.66-3.03, P<0.001). Morbidly obese patients faced worse management for HBP and HFBG, and better management for HBC. It would be interesting to integrate alarm systems to avoid this problem.

A Tool to Quickly Detect Short Hamstring Syndrome in Boys who Play Soccer.

UNLABELLED: There is a lack of studies of alternative techniques differing from the straight leg raise test (SLR) and the passive knee extension test (PKE) to diagnose short hamstring syndrome (SHS). We built a predictive model with simple parameters to diagnose SHS and implemented it in a mobile app. This cross-sectional study analyzed 85 Spanish boys aged 10-16 years who played soccer in 2012. OUTCOMES: SHS (SLR<70° and/or PKE>15°), and grade II SHS (SLR<60° and/or PKE≥35°). Secondary variables: toe-touch test (TT), body mass index (BMI), age, laterality and number of years registered as part of a federation. A risk table implemented in a mobile app was built to estimate the probability of SHS and grade II SHS according to secondary variables. The area under the ROC curve (AUC) was calculated and we constructed risk groups. Scoring factors for SHS: low TT, younger age and lower BMI. AUC: 0.89 (95% CI: 0.82-0.96, p<0.001). Scoring factors for grade II SHS: younger age, higher BMI, left footed and lower TT. AUC: 0.78 (95% CI: 0.68-0.88, p<0.001). We provide a tool with minimum material but with a high discriminatory power to quickly calculate whether a boy who plays soccer has SHS. The models need validation studies.

Suitability of antiplatelet therapy in hypertensive patients.

Antiplatelet therapy (AT) is indicated in hypertensive patients with increased cardiovascular risk. The literature about the adequate or inadequate prescription of AT is scarce. We conducted a prospective descriptive study to quantify therapeutic inertia and non-guideline-recommended prescription (NGRP) of AT (aspirinor clopidogrel or both), and to assess associated factors, calculating the adjusted odds ratios (ORs) from multivariate models. In 2007-2009, 712 primary health-care hypertensive patients in a Spanish region were enrolled. Inertia was defined as the lack of an AT prescription, despite being indicated by guidelines, whereas NGRP was defined as AT prescription when there was no guideline recommendation. We also recorded cardiovascular variables. Inertia and NGRP were quantified for primary and secondary prevention. Of 108 patients in secondary prevention, 53 had inertia (49.1%, 95% confidence interval (CI): 39.6-58.5%). Associated profile: female (OR=0.460, P=0.091), no dyslipidemia (OR=0.393, P=0.048), no coronary heart disease (OR=0.215, P=0.001) and high diastolic blood pressure (OR=1.076, P=0.016). In primary prevention, NGRP was present in 69 of 595 patients (11.6%, 95% CI: 9.0-14.2%). Associated profile: male (OR=1.610, P=0.089), smoking (OR=2.055, P=0.045), dyslipidemia (OR=3.227, P<0.001) and diabetes (OR=2.795, P<0.001). Although certain factors were clearly associated with these phenomena much still remains to be learnt.

Predictive models for all-cause and cardiovascular mortality in type 2 diabetic inpatients. A cohort study.

BACKGROUND: Many authors have analysed premature mortality in cohorts of type 2 diabetic patients, but no analyses have assessed mortality in hospitalised diabetic patients. AIM: To construct predictive models to estimate the likelihood of all-cause mortality and cardiovascular mortality in type 2 diabetic inpatients. DESIGN: Cohort study with follow-up from 2010 to 2014. METHODS: We evaluated mortality in a randomly selected cohort of 112 type 2 diabetic inpatients at the Hospital of Elda (Spain) in 2010-2012. OUTCOMES: all-cause mortality and cardiovascular mortality during the follow-up. Other variables: gender, age, depression, asthma/chronic obstructive pulmonary disease, hypertension, dyslipidemia, insulin, pills, smoking, walking, baseline blood glucose and creatinine. Predictive tables with risk groups were constructed to estimate the likelihood of all-cause mortality and cardiovascular mortality. Calculations were made of the area under the ROC curve (AUC). RESULTS: During the follow-up, 52 inpatients died (46.4%, 95% CI, confidence interval: 37.2-55.7%), 22 because of cardiovascular causes (19.6%, 95% CI: 12.3-27.0%). The mean follow-up time was 2.7 ± 1.5 years. The AUC for the all-cause mortality model was 0.84 (95% CI: 0.77-0.92, p < 0.001). Associated parameters: pills, smoking, walking, gender, insulin and age. The AUC for the cardiovascular mortality model was 0.79 (95% CI: 0.67-0.91, p < 0.001). Associated parameters: age, pills, walking, smoking, depression and insulin. CONCLUSIONS: This study provides tools to predict premature mortality in type 2 diabetic inpatients. However, before their general application they require joint validation by the internal medicine unit, emergency department, primary healthcare unit and endocrinology service to enable better prediction of the prognosis and more adequate decision-taking.

Scaling in complex systems: a link between the dynamics of networks and growing interfaces.

We consider growing interfaces as dynamical networks whose nodes are the discrete points of the interface and the edges the physical interactions among them. We map the points of the interface formed at each time into a graph by means of a visibility algorithm. As the corresponding interfaces grow, their visibility graphs change over time. We show that the visibility graphs are all scale free for each time. We use the variance of the node degrees as a measure of the dynamical properties of these graphs. This magnitude reveals an unexpected scaling behaviour of these graphs in both the number of nodes and time. This enables to define three robust exponents that characterize any type of dynamics with more detail than the classical scaling analysis applied directly to the physical interfaces. To check the feasibility of this approach we study and classify six different dynamical processes and estimate their critical exponents. We conclude that the dynamics of physical systems far from equilibrium can be determined by its corresponding visibility network. Indeed, this methodology is able to discern among dynamical processes that hitherto have been classified in the same universality class according to the scaling analysis of their interfaces.

Impacto de la implantación del programa ASIGNA en un servicio de urgencias hospitalario / Impact of using the ASIGNA computer program in a hospital emergency department

Objetivos: Determinar si el programa informático ASIGNA, basado en la asignación de pacientes por equipo enfermero-médico, reduce el tiempo de espera de los usuarios antes de ser valorados por urgenciólogos del Hospital de General Universitario de Elda. Método: Estudio de intervención no aleatorio, realizado en febrero de 2012 y febrero de 2013, tras la instauración del programa ASIGNA. Se determina como variable principal, el tiempo entre el triaje y la valoración por el urgenciólogo, cuantitativamente en minutos y de forma cualitativa mediante el cumplimiento o no de los tiempos determinados para cada color del triaje Manchester. Las variables secundarias fueron: sexo, edad, color de triaje y la cola o densidad de pacientes. Se utiliza el análisis multivariante de regresión lineal múltiple (tiempo triaje -valoración médica en minutos) y regresión logística (tiempo correcto). Se calculan los indicadores de relevancia clínica. Resultados: ASIGNA aumenta el porcentaje de triaje realizado correctamente del 68,2 al 90,6% (p < 0,001), reduce el tiempo triaje -valoración médica de 63,6 min a 25,2 min (p < 0,001) y reduce la cola de pacientes de 23,8 a 18,0 (p < 0,001). Los indicadores de relevancia clínica fueron: reducción del riesgo absoluto de 0,22 (IC 95%: 0,19-0,26, p < 0,001); reducción del riesgo relativo de 0,70 (IC 95%: 0,64-0,76) y números de pacientes a asistir de 5 (IC 95%: 4-6). ASIGNA multiplica por 4 la posibilidad de atender a un paciente que acuda a urgencias en tiempo correcto. Conclusión: La aplicación del programa ASIGNA obtiene una reducción estadísticamente significativa y clínicamente relevante del tiempo entre triaje y valoración médica

Objective: To determine whether the ASIGNA program for assigning patients to nurse-physician teams expedites time until the initial evaluation of a patient by an emergency physician in the Hospital General Universitario de Elda, Spain. Methods: Nonrandomized study of the effect of using the ASIGNA program from February 2012 to February 2013. The main outcomes were times in minutes until triage and until the initial evaluation by an emergency physician, and the qualitative assessment of compliance or not with times considered reasonable for each color-coded priority category in the Manchester triage system. Secondary variables recorded were sex, age, triage color code, and number of patients waiting. Multivariable linear regression analysis was used to study time between triage and physician evaluation in minutes; logistic regression analysis was used to study the associations with reasonable time according to the Manchester triage system. Indicators of clinical relevance were calculated with 95% confidence intervals (CI). Results: The rates of correctly performed triage increased from 68.2% to 90.6% with use of the ASIGNA program (P < .001). Time from triage to physician evaluation decreased from 63.6 minutes to 25.2 minutes (P < .001), and the number of patients waiting decreased from 23.8 to 18.0 (P<.001). Analysis of indicators of clinical relevance showed improvements in both absolute risk (reduction of 0.22; 95% CI, 0.19-0.26; P < .001) and relative risk (reduction of 0.70; 95% CI, 0.64-0.76). The number of waiting patients fell by 5 (95% CI, 4-6) The ASIGNA program made it possible to attend 4-fold more patients within an amount of time considered reasonable. Conclusions: The use of the ASIGNA program leads to statistically significant and clinically relevant reductions in time from triage to physician evaluation

The effect of pressure on the growth of tumour cell colonies.

This paper describes some experiments on the manner in which external pressure affects cell colony growth in general, and tumour growth in particular. More precisely, our results show that cell colony borders growing under high-pressure conditions have geometrical and dynamical properties that are markedly different from those corresponding to growth under homeostatic, normal pressure conditions. These behaviours are characterized by means of the so-called dynamical exponents of each type of growth. These are shown to correspond to statistical properties of solutions of some stochastic partial differential equations that account for the evolution of the interface between the expanding colony and the surrounding medium.

Pinning of tumoral growth by enhancement of the immune response.

Tumor growth is a surface phenomenon of the molecular beam epitaxy universality class in which diffusion at the surface is the determining factor. This Letter reports experiments performed in mice showing that these dynamics can, however, be changed. By stimulating the immune response, we induced strong neutrophilia around the tumor. The neutrophils hindered cell surface diffusion so much that they induced new dynamics compatible with the slower quenched-disorder Edwards-Wilkinson universality class. Important clinical effects were also seen, including remarkably high tumor necrosis (around 80%-90% of the tumor), a general increase in survival time [the death ratio in the control group is 15.76 times higher than in the treated group (equivalent to a Cox's model hazard ratio of 0.85; 95% confidence interval 0.76-0.95, p=0.004)], and even the total elimination of some tumors.

Clinical status and parasitic infection in a Wichí Aboriginal community in Salta, Argentina.

In a study, carried out in 2000, of the clinical and parasitological status of a Wichi Aboriginal community living in the suburbs of Tartagal, northern Salta, Argentina, 154 individuals were screened for parasitic infections. Ninety-five faecal samples were also obtained from the same population. Ninety-three percent of the subjects were positive for 1 or more of the parasites investigated by direct test and 70.5% of them had parasitic superinfection. The most frequent helminths were Strongyloides stercoralis (50.5%) and hookworm (47.4%). We found low reinfection rates and a long reinfection period after treatment and provision of safe water and sanitation. Serum reactivity of these patients was analysed by enzyme-linked immunosorbent assay and indirect immunofluorescent assay and 22.1% of them had anti-Toxocara antibodies, 16.2% were positive for a complex antigen of Leishmania braziliensis, 29.9% were positive for a complex Trypanosoma cruzi antigen, and 17.5% were positive for a specific Trypanosoma cruzi antigen, Ag 163B6/cruzipain.

Design of a modified uniform redundant-array mask for portable gamma cameras.

Uniform redundant-array masks have been reported as good lenses to form the image of gamma sources, with the correlation between the mask-aperture matrix and the shadows projected on a static position-sensitive detector. We present a modified uniform redundant-array configuration suitable for portable and small-size gamma cameras; its ability to reconstruct the image of several sources is analyzed. We have carried out a Montecarlo simulation of the gamma interactions in the mask, defining the expected response of the correlation process and comparing it with that achieved with the usual uniform redundant-array configurations.

[Experimental model for hemodynamic and metabolic studies of extracorporeal circulation. Apropos of 14 cases]. / Modèle expérimental pour l'étude hémodynamique et métabolique de la circulation extra-corporelle. A propos de 14 cas.

The authors present an homogeneous and stable experimental model, the basic characteristics of which are: 14 extracorporeal bypass with: total bypass; normothermia; total haemodilution; beating heart; continuous flow in dogs anesthetised with chloralose. Three methods were employed: continuous recording of the venous lactate concentration; invasive electromagnetic measurement of the arterial blood flow; measurement of the tissular capillary blood flow with radioactive labelled microspheres. The statistic treatment of the informations gathered confirms that those experimentations took place in normothermia and constant: pH, venous and arterial pressure, cardiac pacing and arterial carotid blood flow. We noticed no modification of the body electrolytic repartition; blood gas variations do not modify haemodynamic conditions. Increase of the lactate concentration, as noticed in the literature, is in relation with a catecholamine hypersecretion and not with an anaerobic tissular function. Tissular capillary blood flow is constant if reported to cardiac index. This model will allow us to compare those results with new series where only one of the basic elements will be modified.

[Isotopic indicators in the diagnosis of malignant pleurisies (author's transl)]. / Les indicateurs isotopiques dans le diagnostic des pleurésies malignes.

The tracers that are used in thoracic pathology have an elective tumoural affinity, present such a special reaction towards pleural effusions that we were led to study Bleomycin labelled with Cobalt 57 in 34 cases of pleurisy of various etiologies. The hyperfixation, circumscribed to the effusion in all these cases, presented a double problem : of radiobiological risk and of diagnostic significance. We tried to solve the last problem by means of a precise protocol applied to 16 cases, quantifying comparatively the specific radio-activity of pleural fluid and serum and studying the evolution of the pleural serous gradient, after injection of 2 mCi of labelled Bleomycin in 16 patients with suspected malignant pleurisy. From this limited study, it appeared that the sero-pleural gradient of the tracer, 24 hours after injection, was very high, above 5 and up to 15 in 7 malignant pleurisies out of 8; between 2 and 4 in others. It was sometimes below 5 and less in effusions, non malignant or doubtful. This gradient decreased very rapidly to reach 0 on the fourth day, except in recurring chronic effusions. Pending the confirmation of results, after a prolonged experiment, this protocol appeared valuable for diagnostic and physiopathological reasons.

[A new associated spondylarthritis: rheumatoid spondylarthritis]. / Une nouvelle spondylarthrite associée: la "spondylarthrite rhumatoïde" existe

The authors analyse 7 cases which presented the criteria of ankylosing spondylarthritis and HLA 27 positivity, together with those of defined or classical rheumatoid polyarthritis with positive results in the latex test and the Waaler-Rose reaction in the joint fluid and/or the serum. The sex distribution, 6 men and 1 woman, was the same as for that disease. The clinical manifestations were very variable, with a predominance of localized, peripheral oligoarthritis in the lower limbs. Repeated iritis occurred in three cases. Two presented subcutaneous nodules on the elbow. All cases showed bilateral sacroiliitis; syndesmophytosis was rare. The overall clinical picture indicated rather a combined spondylarthritis than pure spondylarthritis. It is suggested that the occurrence of spondylarthritis in a subject with the HLA 27 gene might modify the response to the etiological factors of rheumatoid arthritis. These cases may thus be considered as a new type of combined or secondary spondylarthritis.

[Contribution to the scintigraphic diagnosis of malignant endothoracic tumors by 57Co labeled Bleomycin (author's transl)]. / Apport de la bléomycine marquée par le cobalt 57 dans le diagnostic scintigraphique des tumeurs malignes endothoraciques

The authors report the results of the exploration by 57Co Bleomycin scinitigraphy in 97 thoracic tumors. The Bleo-57Co scintigraphy detects primary and secondary malignant tumors underevaluated by classical tests. In the thorax, the radioactive focus are easily detected on account of the light physiological fixation of the Bleo-57Co. It is particularly interesting in the mediastinal tumors where the picture is not covered by cardiovascular interference. Mediastinal, pleural and costal tumors have been explored. Pulmonary tumors give the best results, they fixe in 93% of the case. All the mediastinal tumors have capted the bleomycin but the authors insist on the fact that the fixation was very light even when the tumor was a large one. The exploration of pleural and costal tumors was less interesting. In conclusion, the Bleo-57Co scintigraphy, gives indications about the volume of the tumor and its spread in the organism. By this method, we can diagnose malignancy in tumor. It can be used to survey cancer patients which have been treated. Nevertheless the long half-life (270 days) and the lack of specificity of the Bleo-57Co for the malignant tumors, justify discussion about indications and the results of such an exploration.

[Influence of inaccuracy of certain parameters on dose distribution in telecobalt therapy (author's transl)]. / Influence de l'imprécision de certains paramêtres sur la répartition des doses en télécobalthérapie

Progress in dosimetry and in radiobiology together with the evolution of radiation generators led to adopt very elaborated radiotherapy protocols. However, the therapist should have confidence in these protocols on condition that irradiation parameters are strictly respected. For obvious reasons, this is impossible despite the meticulous rules. In this, paper, we therefore intend to study the role of the angle of incidence on the actual distribution of doses; we also study the inaccuracy of certain parameters recorded during preparation for the therapy or shown during successive irradiation courses. In this paper we retain only errors which can be easily quantified. These are errors concerning the irradiation apparatus (source to skin distance, angle of the rays, field dimension) and those due to factors related to the patient treated: contour measurement, entrance point of rays and positional changes of the patient. The different errors can be associated in various ways for a given therapy protocol. For the same reason, an isodose of a given nominal value will have several curves. All these tracings are lined by two curves which we call "superior and inferior envelops": these border the "incertitude area". It can be said that at the end of the treatment, the given isodose lies in this area; it is however impossible to define its form or exact position. A few examples in the text illustrate these results and show the possible practical angles of incidence. If we assume that errors during successive irradiations are distributed at random, a certain compensation is noted and the "areas of incertitude" decrease. But if the errors are constantly on the same side, as is sometimes the case, the dose distribution can be very different from that predicted in the dosimetric protocol.