Neuropsychological assessment in pediatric epilepsy surgery: A French procedure consensus.

Neuropsychological assessment is a mandatory part of the pre- and post-operative evaluation in pediatric epilepsy surgery. The neuropsychology task force of the ILAE - French Chapter aims to define a neuropsychological procedure consensus based on literature review and adapted for French practice. They performed a systematic review of the literature published between 1950 and 2023 on cognitive evaluation of individuals undergoing presurgical work-up and post-surgery follow-up and focused on the pediatric population aged 6-16. They classified publications listed in the PubMed database according to their level of scientific evidence. The systematic literature review revealed no study with high statistical power and only four studies using neuropsychological scales in their French version. Afterwards, the experts defined a neuropsychological consensus strategy in pediatric epilepsy surgery according to the psychometric determinants of cognitive tests, specificity of epilepsy, surgery context, French culture and literature reports. A common French neuropsychological procedure dedicated to pediatric epilepsy surgery is now available. This procedure could serve as a guide for the pre- and post-surgical work-up in French centers with pediatric epilepsy surgery programs. The main goal is to anticipate the functional risks of surgery, to support the postoperative outcome beyond the seizure-related one, while taking into consideration the plasticity and vulnerability of the immature brain and allowing the possibility of collaborative studies.

French neuropsychological procedure consensus in epilepsy surgery.

INTRODUCTION: Neuropsychological assessment is an integral component of the surgical procedure in patients with epilepsy. As no French consensus for neuropsychological assessment was available, the main goal of this work was to define French neuropsychological procedure consensus in regard to literature review. METHOD: A panel of expert in neuropsychology was created within the framework of the French League Against Epilepsy. A systematic search of publications from 1950 to 2017 listed in PubMed database was conducted leading to a classification of articles according to their level of scientific evidence. French neuropsychological procedure consensus was then carried out with an expert panel of expert. RESULTS: Low scientific evidence of neuropsychological data was reported. A panel of expert proposed a comprehensive neuropsychological assessment procedure including the exploration of intellectual efficiency, long-term memory, short-term and working memory, attention, executive functions, processing speed and motor skills, language, visual processing, praxis, psychobehavioral, and social cognition. DISCUSSION: A common procedure for assessing cognitive and psychobehavioral function is now available in patients with epilepsy undergoing surgical evaluation have been established, they may help to improve the quality of care and the patient experience. This work highlights the need of furthers investigations and the necessity to develop specific tools with normative data.

The role of mechanical stretching in the activation and localization of adhesion proteins and related intracellular molecules.

The molecular complexity of the processes which lead to cell adhesion includes membrane and cytoskeletal proteins, involved in the focal adhesion formation, as well as signaling molecules tightly associated with the main intracellular regulatory cascades (Akt/PKB and MAPK/Erk). Dynamic environments, which create substrate deformations at determined frequencies and timing, have significant influences on adhesion mechanisms and in general in cellular behavior. In this work, we investigated the role of mechanical stretching (10% substrate deformation, 1 Hz frequency applied up to 60 min) on adhesion proteins (vinculin and focal adhesion kinase-FAK), related RhoGTPases (Rac1 and RhoA), and intracellular pathways (Akt/PKB and MAPK/Erk) in terms of activation and membrane recruitment in relation with cytoskeletal changes observed (membrane ruffling and filopodia formation). These changes are due to intracellular molecular rearrangements, acting with sequential concerted dynamics, able to modify the cytoskeletal conformation. The observed cellular response adds some important issues for better understanding the cellular behavior in environment which mimic as close as possible the physiological conditions.

A machine learning approach to explore cognitive signatures in patients with temporo-mesial epilepsy.

We aimed to identify cognitive signatures (phenotypes) of patients suffering from mesial temporal lobe epilepsy (mTLE) with respect to their epilepsy lateralization (left or right), through the use of SVM (Support Vector Machine) and XGBoost (eXtreme Gradient Boosting) machine learning (ML) algorithms. Specifically, we explored the ability of the two algorithms to identify the most significant scores (features, in ML terms) that segregate the left from the right mTLE patients. We had two versions of our dataset which consisted of neuropsychological test scores: a "reduced and working" version (n = 46 patients) without any missing data, and another one "original" (n = 57) with missing data but useful for testing the robustness of results obtained with the working dataset. The emphasis was placed on a precautionary machine learning (ML) approach for classification, with reproducible and generalizable results. The effects of several clinical medical variables were also studied. We obtained excellent predictive classification performances (>75%) of left and right mTLE with both versions of the dataset. The most segregating features were four language and memory tests, with a remarkable stability close to 100%. Thus, these cognitive tests appear to be highly relevant for neuropsychological assessment of patients. Moreover, clinical variables such as structural asymmetry between hippocampal gyri, the age of patients and the number of anti-epileptic drugs, influenced the cognitive phenotype. This exploratory study represents an in-depth analysis of cognitive scores and allows observing interesting interactions between language and memory performance. We discuss implications of these findings in terms of clinical and theoretical applications and perspectives in the field of neuropsychology.

Inhibition of interferon gamma production by peripheral blood mononuclear leukocytes of patients with sarcoidosis. Pathogenic implications.

Interferon gamma (IFN-gamma) production by stimulated peripheral mononuclear leukocytes of 30 patients with sarcoidosis was studied. A significant inhibition (64 percent, 5 to 330 IU/ml vs normal individuals = 1,000 +/- 250 IU/ml) in the IFN-gamma synthesis was found. The inhibition is due to a defect in the circulating monocytes and not in the peripheral T lymphocytes of these patients. This defect in the peripheral IFN-gamma production could be involved in the pathogenesis of this disease.

Treatment and follow-up of HIV-negative multidrug-resistant tuberculosis patients in an infectious diseases reference hospital, Buenos Aires, Argentina.

SETTING: An Argentinean reference hospital specialising in infectious diseases. OBJECTIVE: To assess the outcomes of all human immunodeficiency virus (HIV) negative multidrug-resistant tuberculosis (MDR-TB) patients referred to or diagnosed at Hospital Muñiz. DESIGN: Clinical study for the period 1996-1999, with follow-up until June 2002. RESULTS: One hundred and forty-one adult patients (52.5% female) with resistance to two to seven drugs were studied. Fifty patients (35.5%) had not been treated previously. The most frequently used second-line drugs were 5-F-quinolones, cycloserine and ethionamide in susceptibility based individually tailored three- to five-drug regimens. Hospital admission was associated with treatment success. Forty-five episodes of severe toxicity occurred. Treatment was successful in 51.8% of cases, but follow-up of 73 patients yielded 11.9% relapse. The mortality rate was 19.1% and default was 19.9%. Logistic regression analysis was statistically significant for treatment success in relation to patient admission, residence and resistance pattern. CONCLUSION: The burden of MDR-TB in this setting--prolonged infection, treatment cost and difficulties, low rates of cure and treatment adherence and high rates of fatality and relapse--can be improved by strengthening TB control programme activities and fighting against poverty and HIV/AIDS.

[Evaluation and treatment of interstitial lung disease in Argentine]. / Evaluación y tratamiento de la enfermedad intersticial pulmonar en la Argentina.

To determine the availability and usual management of interstitial lung diseases (ILD) in our country, the Section of Interstitial Lung Diseases of the Argentine Association for Respiratory Medicine (AAMR) made a survey about diagnostic methodology and treatment of ILD. A total of 115 answers were obtained (38.5%), 43% of them among physicians living in the provinces. Availability of diffusing capacity of the lung for carbon monoxide test (DLCO) is limited: 25.4% never have access to it and 35.6% can seldom use it. Availability to thoracic CT scan is wider: 85% may use if often (32.4%) or always (52.6%). Bronchoscopy is commonly available in 87.7% of the physicians either often (21.9%) or always (65.8%). However, only 20.2% perform BAL and 13.1% transbronchial biopsy in every patient. Only 16.6% perform open lung biopsy or thoracoscopic biopsy in all or most of their patients. Sixty eight percent of physicians who always have availability of DLCO perform it in every patient but only 7.1% of those who seldom have access to DLCO do so (p = 0.0003). Availability of bronchoscopy does not have any influence on the decision of performing BAL or transbronchial biopsy. Frequency of use of surgical biopsy or treatment with immunosuppressive drugs was not influenced by any variable. We conclude that there is a current trend to underuse diagnostic resources for ILD in Argentina. Limitations in availability are relevant regarding DLCO. An effort from the health authorities to centralize the management of patients with ILD would allow to study and treat them according to international recommendations.

Effects of handling and storage on sterile dental instruments.

The microbial contamination post-sterilization of dental instruments has been the object of permanent study. The aim of the present study was to evaluate factors affecting long-term sterility of dental instruments sterilized in the dry-oven or autoclave at the Central Sterilizing Service of the School of Dentistry, University of Buenos Aires stored under room temperature and humidity conditions. Half of the 192 samples were placed in standard closed metal containers and sterilized in a dry-oven (D.O), and the remaining half were placed in perforated metal containers and sterilized in an autoclave (A). All the samples were placed in sterilizing paper bags for medical use. Post sterilization, each group (DO and A) was divided into: Group I: minimal handling (control); Group II: wrapping torn mechanically (1 cm); Group III: wrapping torn manually (1 cm). All the samples were stored a closed cabinet. Contamination was evaluated at 30 and 180 days, by seeding under aerobic and anaerobic conditions. Temperature was monitored throughout the experiment, and ranged between 20 degrees C and 31 degrees C (x: 24 degrees C +/- 3.9). Humidity was measured with a digital hygrometer, and ranged between 40% and 60% (x: 54% +/- 10). Group I evidenced no microbial contamination, unlike Groups II and III. Our results evidence that 1) dry oven or autoclave sterilized material that is handled properly during storage remains sterile regardless of variations in temperature and humidity; 2) improper handling affects sterility, and contamination is time-dependent.

Cardiovascular biomaterials: when the inflammatory response helps to efficiently restore tissue functionality?

The evaluation of biological host response to implanted materials permits the determination of the safety and biocompatibility of biomedical devices, prostheses and biomaterials. Once a biomaterial is introduced into the body to a corresponding implant site, a sequence of events occurs promoting the activation of inflammatory mediators such as leukocytes and the release of signaling molecules such as cytokines and growth factors, evoking an inflammatory and wound healing process. This review examines the cellular and molecular mechanisms involved in the foreign body reaction, especially how cytokines impact the overall inflammatory response to devices. It also reviews how these events can be modulated by the physical and chemical properties of the biomaterials such as wettability, chemistry and geometry of surface. Particular attention is dedicated to the cardiovascular field, where the use of synthetic polymers has several limitations such as thrombogenicity and risk of infection. New materials and strategies to improve biomaterial characteristics are discussed.

Rehabilitation of verbal memory by means of preserved nonverbal memory abilities after epilepsy surgery.

We present a patient with epilepsy who underwent left anterior temporal cortex resection, sparing the hippocampus, to stop drug-refractory seizures. Given that one year after surgery the patient showed verbal memory difficulties, we proposed a short (twelve weeks) and intensive (two times a week) training based on visual imagery strategies as the nonverbal memory abilities were preserved. Neuropsychological and fMRI assessments were performed before and after rehabilitation to evaluate the cognitive progress and cerebral modifications induced by this rehabilitation program. Our results showed that the rehabilitation program improved both scores for verbal memory and the everyday quality of life. Changes in cerebral activity highlighted by fMRI suggest that the program might have facilitated the development of compensatory strategies, as reflected by the shift of activation from the anterior to the posterior cerebral network during a verbal memory task. One year after the rehabilitation program, the patient reported using mental imagery in everyday life for routine and professional activities. Although supplementary evidence is necessary to increase the robustness of these findings, this case report suggests that an efficient rehabilitation program is feasible and (a) should be based on the individual cognitive profile and on the preserved cognitive abilities, (b) can be short but intensive, (c) can be applied even months after the lesion occurrence, and (d) can induce a positive effect which may be sustainable over time.

Biological evaluation of materials for cardiovascular application: the role of the short-term inflammatory response in endothelial regeneration.

Because of their suitable bio-mechanical properties, polymeric materials, such as Poly(L-lactic acid) (PLLA), and poly (lactic-co-glycolic acid) (PLGA), are often used in the biomedical field, in particular for cardiovascular applications. Implanted materials induce several events related to the inflammatory reaction, such as macrophage adhesion and activation with following cytokine release. This work considered the effect of macrophage adhesion and related cytokine release on endothelial cells (PAOEC) proliferation and migration. Slight differences have been shown by the macrophages reaction when in contact with PLLA, PLGA, or PLLA/PLGA blend. However, these differences showed to differently enhance endothelial cells behavior in terms of wound healing. These data suggest the inflammatory reaction as a useful way to consider concerning materials biocompatibility, in order to optimize the endothelial regeneration following vascular prosthetic implants.

Difficult clinical management of anti-tuberculosis DRESS syndrome.

We describe 11 cases of anti-tuberculosis DRESS (drug-related rash with eosinophilia and systemic symptoms) syndrome, a potentially serious complication of treatment that led to interruption of treatment for prolonged periods, systemic corticosteroid use and the resumption of treatment with less effective regimens. All patients had rash and toxic hepatitis, one died of multi-organ failure and, contrary to expectations, the evolution of tuberculosis (advanced in most cases) did not progress under corticosteroid treatment. The drug most frequently involved was rifampicin, while retreatment schemes included, in most cases, levofloxacin, ethambutol, streptomycin and cycloserine.

PP043. Do women know what pre-eclampsia is? What is the level of knowledge of the disease in a small population connected to a social net?

INTRODUCTION: Pre-eclampsia is responsible for a great number of maternal deaths in our country. Even in urban areas that, theoretically, has more access to information and more medical assistance possibilities, much more women have very severe cases that could be avoided. Many initiatives to reduce this problem include effective women participation in that item, making us to believe that actual information access would allow precocious detection of the problem, leading to reduction of the maternal and perinatal risks. OBJECTIVES: To investigate a specific female population about how much they understand about the disease and its risks. METHODS: Using the social net Facebook®, a survey was developed for online use, where direct questions related to pre-eclampsia were made. The questions involved information about age, times of pregnancy, knowledge about pre-eclampsia and their risks. It was considered an inclusion criterion the women who decided to participate in the survey spontaneously, and their identity was preserved. This form was sent to 1000 women, and 120 fully answered the questions and they were put under analysis. RESULTS: The studied group had average age between 22 and 35years. From the total, 107 (89.6%) had at least initiated high school, and the rest (11%) said that they had at least finished elementary school. From the analyzed data, it was found that 60 (50%) of the interviewed women, did not know anything about the subject. The rest said that they had some knowledge about the topic. From those, 14 (23%) had already heard about pre-eclampsia, but did not know what was it, 44 (73%) had a vaguely notion but did not know about the risks, and just 2 (4%) gave the entirely correct definition and knew about its implications. From all, 24 (20%) from the interviewed had at least once been pregnant, and 15 from those, had never heard about the pathology. CONCLUSION: Despite of the impact that pre-eclampsia represents on mother and baby's health, our results show that information in the studied group, is poor. The studied group has naturally more access to information, showing us that the situation is even more concerning. We believe that it is necessary to apply instruments that could redefine, in a greater way, the real information level to the female population in all levels of assistance. To enlarge the health politics, and increase its efficiency through informed women, seem to us, a fundamental strategy to qualify assistance and enhance maternal and prenatal safety. In an era that social nets had changed human behavior, why should not we use it as an efficient tool to promote life quality?

The biological response of poly(L-lactide) films modified by different biomolecules: role of the coating strategy.

The interactions between the surface of synthetic scaffolds and cells play an important role in tissue engineering applications. To improve these interactions, two strategies are generally followed: surface coating with large proteins and surface grafting with small peptides. The proteins and peptides more often used and derived from the extracellular matrix, are fibronectin, laminin, and their active peptides, RGD and SIKVAV, respectively. The aim of this work was to compare the effects of coating and grafting of poly(L-lactide) (PLLA) films on MRC5 fibroblast cells. Grafting reactions were verified by X-ray photoelectron spectroscopy. Cell adhesion and proliferation on coated and grafted PLLA surfaces were measured by cell counting. Vinculin localization and distribution were performed on cell cultured on PLLA samples using a fluorescence microscopy technique. Finally, western blot was performed to compare signals of cell adhesion proteins, such as vinculin, Rac1, and RhoA, as well as cell proliferation, such as PCNA. These tests showed similar results for fibronectin and laminin coated PLLA, while RGD grafting is more effective compared with SIKVAV grafting. Considering the overall view of these results, although coating and grafting can both be regarded as effective methods for surface modification to enhance cell adhesion and proliferation on a biomaterial, RGD grafted PLLA show better cell adhesion and proliferation than coated PLLA, while SIKVAV grafted PLLA show similar adhesion but worse proliferation. These data verified different biological effects depending on the surface modification method used.

GLP-1 receptor agonists and HBA1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials.

OBJECTIVE: Glucagon-like peptide-1 (GLP-1) receptor agonists are available for the treatment of type 2 diabetes. We assessed the efficacy of exenatide and liraglutide to reach the HbA(1c) target of <7% in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic search for randomized controlled trials (RCTs) involving GLP-1 agonists through September 2010. RCTs were included if they lasted at least 12 weeks, included 30 patients or more, and reported the proportion of patients reaching the HbA(1c) target of <7%. RESULTS: A total of 25 RCTs reporting 28 comparisons met the selection criteria, which included 9771 study participants evaluated for the primary endpoint, 5083 treated with a GLP-1 agonist and 4688 treated with placebo or a comparator drug. GLP-1 agonists showed a statistically significant reduction in HbA(1c) compared to placebo and the proportion of participants achieving the HbA(1c) goal <7% was 46% for exenatide, 47% for liraglutide, and 63% for exenatide LAR (long-acting release). Moreover, the reduction of the HbA(1c) level and the rate of HbA(1c) goal attainment were higher for both exenatide LAR and liraglutide, as compared to comparator drugs. Higher rates of hypoglycemia with exenatide b.i.d. and liraglutide compared to placebo were associated with the concomitant use of a sulfonylurea. Exenatide b.i.d. and liraglutide were associated with weight loss compared to placebo or other antidiabetic drugs. Baseline HbA(1c) was the best predictor for achievement of A1c target (overall weighted R(2) value = 0.513, p < 0.001). CONCLUSIONS: A greater proportion of patients with type 2 diabetes can achieve the HbA(1c) goal <7% with GLP-1 agonists compared to placebo or other antidiabetic drugs; in absolute terms, exenatide LAR was best for the attainment of the HbA(1c) goal.

Linezolid treatment for gram-positive infections: a retrospective comparison with teicoplanin.

In randomized studies linezolid, indicated for Gram-positive infections, was as effective as teicoplanin in critical ill patients or was superior to teicoplanin in skin infection, pneumonia and bacteremia. We performed a 2-year comparative, retrospective study of patients treated with linezolid or teicoplanin in a single hospital for the same indications. We collected information about the type of infection, the responsible pathogen, therapy administered before study drugs, antibiotic associated with the study drugs, length of hospital stay (LOS), adverse events and outcome of the infections. The aim of the study was to evaluate the efficacy of linezolid in this retrospective patients series. Overall we identified 169 patients treated with linezolid and 91 with teicoplanin. Response to therapy, (resolution or improvement of infection) was better in patients treated with linezolid compared to teicoplanin (83.9% versus 69.2%, p=0.002). Response to therapy by type of pathogen showed the superior efficacy of linezolid against Staphylococcus aureus (including MRSA) and enterococci; although not statistically significant because of the small number of patients enrolled, they were close to significance (p<0.056 for S. aureus, p<0.055 for MRSA, p<0.061 for enterococci). Overall LOS in linezolid-treated patients was 4.6 days (p<0.041) less. Empirical use of linezolid reduced lOS by 6 days (p<0.038), especially in VAP and bacteremia patients (p<0.05). Mortality due to infection was 9.8% in both groups, and adverse events were most frequently documented in linezolid-treated patients. Linezolid was clinically superior to teicoplanin in the treatment of Gram-positive infections.

The perspectives of current trainees in combined internal medicine-pediatrics. Results of a national survey.

OBJECTIVE: To gather information from combined internal medicine-pediatric residents about their application process for residency, their perceptions of the stressors during residency, and their future plans. DESIGN: Survey of all combined internal medicine-pediatric residents-in-training in the 1989-1990 academic year. PARTICIPANTS: Fifty-four percent of residents-in-training responded to the survey, representing 70% of the programs. RESULTS: Combined residents often investigate and rank other generalist residences. However, internal medicine is significantly (P < .005) considered more often than pediatrics or family medicine. Sixty percent of combined residents do not anticipate further training beyond the 4 years and expect to practice both specialties. The majority of those interested in a subspecialty expect to continue to combine internal medicine and pediatrics in their subspecialty practice. Switching services during the residency engenders stress. Factors that decrease stress include more frequent switches and increasing seniority. Switching from pediatrics to internal medicine is more stressful (P < .0001) than switching to pediatrics from internal medicine. The residents considered ambulatory training sites and a specific coordinator for the program to be the most important features of the residency. CONCLUSIONS: Combined internal medicine-pediatric programs continue to attract a small cohort of well-qualified US medical school graduates, the majority of whom intend to practice as generalists in both pediatrics and internal medicine.

Insulin resistance as a modifier of the relationship between dietary fat intake and weight gain.

OBJECTIVE: To investigate whether insulin resistance modifies the rate of weight gain associated with a high percent of energy intake from dietary fat. DESIGN: Longitudinal, observational population study. SUBJECTS: A total of 782 nondiabetic Hispanic and non-Hispanic white free-living adult residents of the San Luis Valley in Colorado. MEASUREMENTS: Subjects were seen up to three times over a 14-y period. Weight, height, fasting insulin and glucose, diet by 24 h recall, and self-reported physical activity were collected at each visit. RESULTS: Percentage of energy intake from dietary fat was positively associated with weight gain over time (P=0.0103). High intake of dietary fat was more strongly related to weight gain in women than in men, and in those with lower total energy intake levels. The relationship between weight change and relative macronutrient intake also varied by baseline insulin sensitivity (P=0.0025). Weight gain over time in individuals with relative insulin resistance at baseline, as measured by QUICKI, was the greatest among those who consumed a higher percent of energy from fat. CONCLUSION: Percentage of total intake from dietary fat predicts weight change independent of total energy intake. Nondiabetic, insulin-resistant individuals are particularly susceptible to the weight gain associated with high levels of dietary fat intake. Further investigation into the relationship between insulin resistance, diet, and weight gain is warranted.

[South American blastomycosis. Apropos of new cases]. / Blastomycose sud-américaine. A propos de nouvelles observations.

Twenty-seven cases of South American blastomycosis are reported. Pulmonary lesions predominate and the diagnosis rests on the findings of Paracoccidioides brasiliensis in sputum and tissues. Serological examinations (complement fixation and immunodiffusion) are also useful. Treatment includes sulphonamides, imidazole derivatives and, in cases resistant to these drugs, Amphotericin B. Surgery is limited to abscesses, bone lesions and bronchial stenoses.