Prospective evaluation of three point of care devices for glycemia measurement in a neonatal intensive care unit.

Hypoglycemia, if recurrent, may have severe consequences on cognitive and psychomotor development of neonates. Therefore, screening for hypoglycemia is a daily routine in every facility taking care of newborn infants. Point-of-care-testing (POCT) devices are interesting for neonatal use, as their handling is easy, measurements can be performed at bedside, demanded blood volume is small and results are readily available. However, such whole blood measurements are challenged by a wide variation of hematocrit in neonates and a spectrum of normal glucose concentration at the lower end of the test range. We conducted a prospective trial to check precision and accuracy of the best suitable POCT device for neonatal use from three leading companies in Europe. Of the three devices tested (Precision Xceed, Abbott; Elite XL, Bayer; Aviva Nano, Roche), Aviva Nano exhibited the best precision. None completely fulfilled the ISO-accuracy-criteria 15197: 2003 or 2011. Aviva Nano fulfilled these criteria in 92% of cases while the others were <87%. Precision Xceed reached the 95% limit of the 2003 ISO-criteria for values ≤4.2 mmol/L, but not for the higher range (71%). Although validated for adults, new POCT devices need to be specifically evaluated on newborn infants before adopting their routine use in neonatology.

Active mitral ring for post-surgical remote correction of residual mitral regurgitation on the beating heart.

OBJECTIVES: Residual mitral regurgitation after valve repair worsens patients' clinical outcome. Postimplant adjustable mitral rings potentially address this issue, allowing the reshaping of the annulus on the beating heart under echocardiography control. We developed an original mitral ring allowing valve geometry remodelling after the implantation and designed an animal study to assess device effectiveness in correcting residual mitral regurgitation. METHODS: The device consists of two concentric rings: one internal and flexible, sutured to the mitral annulus and a second external and rigid. A third conic element slides between the two rings, modifying the shape of the flexible ring. This sliding element is remotely activated with a rotating tool. Animal model: in adult swine, under cardio pulmonary bypass and cardiac arrest, we shortened the primary chordae of P2 segment to reproduce Type III regurgitation and implanted the active ring. We used intracardiac ultrasound to assess mitral regurgitation and the efficacy of the active ring to correct it. RESULTS: Severe mitral regurgitation (3+ and 4+) was induced in eight animals, 54 ± 6 kg in weight. Vena contracta width decreased from 0.8 ± 0.2 to 0.1 cm; proximal isovelocity surface area radius decreased from 0.8 ± 0.2 to 0.1 cm and effective regurgitant orifice area decreased from 0.50 ± 0.1 to 0.1 ± 0.1 cm(2). Six animals had a reversal of systolic pulmonary flow that normalized following the activation of the device. All corrections were reversible. CONCLUSIONS: Postimplant adjustable mitral ring corrects severe mitral regurgitation through the reversible modification of the annulus geometry on the beating heart. It addresses the frequent and morbid issue of recurrent mitral valve regurgitation.

Maladie de Behçet: d'Hippocrate aux antagonistes du TNF-alpha

Behçet's disease is a systemic vasculitis affecting small and large vessels (arteries, veins, veinules), characterized by recurrent oral ulcerations, genital ulcerations, inflammation of the eye and skin lesions. It can also involve articulations, central nervous system and gastro-intestinal tract. The etiology of this disease is still unknown, but the most largely discussed hypothesis is that of an important inflammatory response triggered by an infectious agent in a genetically susceptible host. The diagnostic is a based on clinical elements, because no specific diagnostic test exists. The treatment of Behçet's disease is depending on the clinical involvement and has been enlarged in recent years by TNF-alpha-blockers which constitute undoubtedly an important progress in the management of this complex disease.

Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide.

PURPOSE: Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). This phase II study was performed to determine the safety, tolerability, and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM. PATIENTS AND METHODS: Sixty-four patients were enrolled onto this open-label, phase II trial. Temozolomide (75 mg/m(2)/d x 7 d/wk for 6 weeks) was administered orally concomitant with fractionated radiotherapy (60 Gy total dose: 2 Gy x 5 d/wk for 6 weeks) followed by temozolomide monotherapy (200 mg/m(2)/d x 5 days, every 28 days for six cycles). The primary end points were safety and tolerability, and the secondary end point was overall survival. RESULTS: Concomitant radiation plus temozolomide therapy was safe and well tolerated. Nonhematologic toxicities were rare and mild to moderate in severity. During the concomitant treatment phase, grade 3 or 4 neutropenia, thrombocytopenia, or both were observed in 6% of patients, including two severe infections with Pneumocystis carinii. During adjuvant temozolomide, 2% and 6% of cycles were associated with grade 3 and 4 neutropenia or thrombocytopenia, respectively. Median survival was 16 months, and the 1- and 2-year survival rates were 58% and 31%, respectively. Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome. CONCLUSION: Continuous daily temozolomide and concomitant radiation is safe. This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma. Further investigation is warranted, and a randomized trial is ongoing.

Drug Resistance Patterns among Hospitalized Tuberculous Patients in Rio de Janeiro, Brazil, 1993-1994

The purpose of this study was to analyze the prevalence and risk factors for drug resistance among hospitalized patients in two tertiary care centers, an acquired immunodeficiency syndrome (AIDS) reference center and a sanatorium, in Rio de Janeiro, Brazil. From 1993-1994, 389 patients were diagnosed as having tuberculosis (TB). Isolates from 265 patients were tested for in vitro susceptibility to rifampin and isoniazid. Resistance to one or more drugs was detected in 44 patients (16.6%) and was significantly more common among recurrent cases in both hospitals (p=0.03 in the AIDS center and p=0.001 in the sanatorium). Twenty seven patients (10.2%) had isolates resistant to both isoniazid and rifampin. Multi-drug resistance was associated with human immunodeficiency virus (HIV) infection among patients who had never been treated for TB. In conclusion, drug-resistant TB is high in hospitalized patients in Rio de Janeiro, especially among HIV infected patients. Therefore, measures to control TB and prevent nosocomial transmission need urgently to be set up in the Brazilian hospitals.

Cricotracheal resection for pediatric subglottic stenosis.

Until recently, cricotracheal resection (CTR) has not been commonly accepted as a treatment modality for severe subglottic stenosis in the pediatric age group. The reasons have included the risk of a possible dehiscence at the site of the anastomosis, the likelihood of injury to the recurrent laryngeal nerves, and the interference with normal growth of the larynx. Thirty-eight infants and children with a severe subglottic stenosis underwent a partial cricoid resection with primary thyrotracheal anastomosis. Thirty-three patients were tracheotomy-dependent at the time of surgery and 34 were referred cases; 27 were classified as grade III, and 10 as grade IV stenoses according to new Cotton's classification. Nineteen patients were younger than 3 years of age at the time of surgery. The tracheotomy was resected during the surgical procedure in 21 cases. Decannulation was achieved in 36/38 cases after an open procedure. There is one complete restenosis and one good result awaiting decannulation after further surgery for a Pierre Robin syndrome. The authors experienced no lesion of the recurrent laryngeal nerves and no fatality. Thirty-one patients show no exertional dyspnea, three a slight stridor while exercising, and two patients are not decannulated. The postoperative follow-up in longer than 10 years in eight cases. All patients show a normal growth of the larynx and trachea. Compared to laryngotracheoplasties, CTR gives better results for severe subglottic stenosis. This operation should become the treatment of choice for severe (grade III and IV) subglottic stenosis in infants and children.

Elimination of vector-borne transmission of Chagas disease

The control of the vector-borne transmission of Chagas disease in Brazil was organized as a national program in 1975, when two large entomological and sero-epidemiological surveys were conducted in the country in order to identify areas at highest risk of transmission and to guide inerventions regarding the chemical treatment of domestic vectors of the disease. The authors present the baseline data gathered through these studies and compare them with more recent data. The evaluation performed shows that the transmission by Triatoma infestans is virtually interrupted and that the transmission by other native species of triatominae from different regions of the country is possibly very low. It is emphasized the need to maintain permanent actions of entomological surveillance in order to prevent recurrent transmission.

Inferior vena cava syndrome due to Echinococcus multilocularis.

Alveolar echinococcosis is an invasive, tumor-like zoonosis, accidentally transmitted to humans. We present a case of recurrent inferior vena cava (IVC) syndrome due to alveolar echinococcosis and strongly suspected on transthoracic echocardiographic examination.

Estràtegies de gestió per al manteniment de la biodiversitat a la sabana brasilera: control d'especies exòtiques amb foc

Report for the scientific sojourn at the Instituto de Biociências, of the Universidade de Sao Paulo, Brazil, from 2007 to 2009. African exotic grasses, used as forage crops for cattle, found optimal conditions in Brazilian savannas for their spread. They established as invasive grasses in almost all conservation units, becoming a serius threat to native biote and to most ecological processes. Fire is a cyclical event in Brazilian savannas and can be used as a management tool for enhancing competitivity of native grasses and controlling exotic grasses. Seeking for alternatives for the management of these grasses, this study investigates the effect of recurrent burnings in different periods of the year (fire regimes) on: distribution patterns of exotic grasses and their associations wotih native grasses, the local edaphic characteristics, the nutrient pool of the aerial biomass of both native and exotic grasses, and soil seed banks. This project is held on the IBGE Ecological Reserve, in Brasília (Brazil), in an area destined specifically for research of fire effects on brazilian savannas. The project quantifies: aerial biomass of native and exotic grasses, soil seed bank of exotic grasses, nutrient pool in soil and also in grasses tissues. Spatial relationships for any association between species, as well as for nutrient pools in soil and in plant tissues will be established. A better understanding of these processes will provide useful tools for adopting specific policies on the management of exotic grasses in Brazilian savanna.

A dendritic cell vaccine pulsed with autologous hypochlorous Acid-oxidized ovarian cancer lysate primes effective broad antitumor immunity: from bench to bedside.

PURPOSE: Whole tumor lysates are promising antigen sources for dendritic cell (DC) therapy as they contain many relevant immunogenic epitopes to help prevent tumor escape. Two common methods of tumor lysate preparations are freeze-thaw processing and UVB irradiation to induce necrosis and apoptosis, respectively. Hypochlorous acid (HOCl) oxidation is a new method for inducing primary necrosis and enhancing the immunogenicity of tumor cells. EXPERIMENTAL DESIGN: We compared the ability of DCs to engulf three different tumor lysate preparations, produce T-helper 1 (TH1)-priming cytokines and chemokines, stimulate mixed leukocyte reactions (MLR), and finally elicit T-cell responses capable of controlling tumor growth in vivo. RESULTS: We showed that DCs engulfed HOCl-oxidized lysate most efficiently stimulated robust MLRs, and elicited strong tumor-specific IFN-γ secretions in autologous T cells. These DCs produced the highest levels of TH1-priming cytokines and chemokines, including interleukin (IL)-12. Mice vaccinated with HOCl-oxidized ID8-ova lysate-pulsed DCs developed T-cell responses that effectively controlled tumor growth. Safety, immunogenicity of autologous DCs pulsed with HOCl-oxidized autologous tumor lysate (OCDC vaccine), clinical efficacy, and progression-free survival (PFS) were evaluated in a pilot study of five subjects with recurrent ovarian cancer. OCDC vaccination produced few grade 1 toxicities and elicited potent T-cell responses against known ovarian tumor antigens. Circulating regulatory T cells and serum IL-10 were also reduced. Two subjects experienced durable PFS of 24 months or more after OCDC. CONCLUSIONS: This is the first study showing the potential efficacy of a DC vaccine pulsed with HOCl-oxidized tumor lysate, a novel approach in preparing DC vaccine that is potentially applicable to many cancers. Clin Cancer Res; 19(17); 4801-15. ©2013 AACR.

Characterization of metabolites in infiltrating gliomas using ex vivo &supl;H high-resolution magic angle spinning spectroscopy.

Gliomas are routinely graded according to histopathological criteria established by the World Health Organization. Although this classification can be used to understand some of the variance in the clinical outcome of patients, there is still substantial heterogeneity within and between lesions of the same grade. This study evaluated image-guided tissue samples acquired from a large cohort of patients presenting with either new or recurrent gliomas of grades II-IV using ex vivo proton high-resolution magic angle spinning spectroscopy. The quantification of metabolite levels revealed several discrete profiles associated with primary glioma subtypes, as well as secondary subtypes that had undergone transformation to a higher grade at the time of recurrence. Statistical modeling further demonstrated that these metabolomic profiles could be differentially classified with respect to pathological grading and inter-grade conversions. Importantly, the myo-inositol to total choline index allowed for a separation of recurrent low-grade gliomas on different pathological trajectories, the heightened ratio of phosphocholine to glycerophosphocholine uniformly characterized several forms of glioblastoma multiforme, and the onco-metabolite D-2-hydroxyglutarate was shown to help distinguish secondary from primary grade IV glioma, as well as grade II and III from grade IV glioma. These data provide evidence that metabolite levels are of interest in the assessment of both intra-grade and intra-lesional malignancy. Such information could be used to enhance the diagnostic specificity of in vivo spectroscopy and to aid in the selection of the most appropriate therapy for individual patients.

Les malformations utérines: diagnostic, pronostic et prise en charge en 2008 [Congenital uterine anomalies: diagnosis, prognosis and management in 2008].

The müllerian anomalies or congenital uterine anomalies are relatively frequent if we keep in mind that 3-4% of our female patients present with a müllerian anomaly, although many among them are asymptomatic. It is important to evoke this diagnosis for all patients with a history of recurrent miscarriage, late abortion and premature delivery, for the adolescent consulting for primary amenorrhea, dysmenorrhea or dyspareunia as well as for the woman consulting for infertility. We will review pathogenesis, diagnostic methods, standard classification with a description of the different types of congenital uterine anomalies and the recommended management.

A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders.

BACKGROUND: The recurrent ~600 kb 16p11.2 BP4-BP5 deletion is among the most frequent known genetic aetiologies of autism spectrum disorder (ASD) and related neurodevelopmental disorders. OBJECTIVE: To define the medical, neuropsychological, and behavioural phenotypes in carriers of this deletion. METHODS: We collected clinical data on 285 deletion carriers and performed detailed evaluations on 72 carriers and 68 intrafamilial non-carrier controls. RESULTS: When compared to intrafamilial controls, full scale intelligence quotient (FSIQ) is two standard deviations lower in carriers, and there is no difference between carriers referred for neurodevelopmental disorders and carriers identified through cascade family testing. Verbal IQ (mean 74) is lower than non-verbal IQ (mean 83) and a majority of carriers require speech therapy. Over 80% of individuals exhibit psychiatric disorders including ASD, which is present in 15% of the paediatric carriers. Increase in head circumference (HC) during infancy is similar to the HC and brain growth patterns observed in idiopathic ASD. Obesity, a major comorbidity present in 50% of the carriers by the age of 7 years, does not correlate with FSIQ or any behavioural trait. Seizures are present in 24% of carriers and occur independently of other symptoms. Malformations are infrequently found, confirming only a few of the previously reported associations. CONCLUSIONS: The 16p11.2 deletion impacts in a quantitative and independent manner FSIQ, behaviour and body mass index, possibly through direct influences on neural circuitry. Although non-specific, these features are clinically significant and reproducible. Lastly, this study demonstrates the necessity of studying large patient cohorts ascertained through multiple methods to characterise the clinical consequences of rare variants involved in common diseases.

A novel tool to analyze MRI recurrence patterns in glioblastoma.

At least 10% of glioblastoma relapses occur at distant and even contralateral locations. This disseminated growth limits surgical intervention and contributes to neurological morbidity. Preclinical data pointed toward a role for temozolomide (TMZ) in reducing radiotherapy-induced glioma cell invasiveness. Our objective was to develop and validate a new analysis tool of MRI data to examine the clinical recurrence pattern of glioblastomas. MRIcro software was used to map the location and extent of initial preoperative and recurrent tumors on MRI of 63 patients in the European Organisation for Research and Treatment of Cancer (EORTC) 26981/22981/National Cancer Institute of Canada (NCIC) CE.3 study into the same stereotaxic space. This allowed us to examine changes of site and distance between the initial and the recurrent tumor on the group level. Thirty of the 63 patients were treated using radiotherapy, while the other patients completed a radiotherapy-plus-TMZ treatment. Baseline characteristics (median age, KPS) and outcome data (progression-free survival, overall survival) of the patients included in this analysis resemble those of the general study cohort. The patient groups did not differ in the promoter methylation status of methyl guanine methyltransferase (MGMT). Overall frequency of distant recurrences was 20%. Analysis of recurrence patterns revealed no difference between the groups in the size of the recurrent tumor or in the differential effect on the distance of the recurrences from the preoperative tumor location. The data show the feasibility of groupwise recurrence pattern analysis. An effect of TMZ treatment on the recurrence pattern in the EORTC 26981/22981/NCIC CE.3 study could not be demonstrated.

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Musculoskeletal disorders (MSD) are the most prevalent pain disorders in industrialized countries, and their costs can represent up to 2% of gross national product. MSD are often work associated and recurrent and may lead to disability. In occupational health we are interested in the opposite process : in the return to work (RTW). Different models of disability and RTW exist with different conceptions of psychosocial factors. We therefore propose to analyze the influence of factors from work, patient, health care providers, and broader societal domains along the different phases of the MSD process, adopting a biopsychosocial approach. The analysis of risk factors for the different phases of MSD indicate that work stress factors have an impact on the occurrence of MSD and RTW with MSD, but their effect is low to moderate and nonspecific. Physical work demands, work place adaptation, and pain experience are much stronger predictors of RTW. Lack of modified or adapted work is one of the major factors that hinder RTW. The longer the pain lasts, the longer the patient is out of work, the more personal factors and broader context factors become dominant. There is a clear lack of RTW studies concerning neck and upper limb pain. MSD and especially chronic MSD should be viewed as public health concerns, implying a wider socio-economic and insurance and disability problem. Adequate medical support tailored to the different dimensions and phases of MSD must be on offer, and work accommodations must be promoted and supported.