Pathologic differentiation between lupus and nonlupus membranous glomerulopathy

Pathologic differentiation between lupus and nonlupus membranous glomerulopathy. The following clinical and pathologic features were evaluated in 170 patients with electron microscopically documented membranous glomerulopathy: age, sex, race, American Rheumatism Association lupus criteria, serum ANA, serum complement, glomerular hypercellularity, stage of subepithelial dense deposits, endothelial tubuloreticular inclusions, tubular basement membrane deposits, tissue ANA, glomerular deposition of IgG, IgM, IgA, C3, C4, and C1q. At the time of biopsy 148 patients had no clinical evidence for lupus, and 22 had a clinical diagnosis of lupus. Six additional patients eventually developed overt lupus after an average of 12 months. Incidences of serologic and pathologic features in lupus as compared with nonlupus membranous glomerulopathy were determined. These data were used to calculate sensitivity, specificity, positive and negative predictive values, and overall efficiency of each parameter in differentiating between lupus and nonlupus membranous glomerulopathy. In general, serologic, morphologic and immunohistopathologic features are more accurate at ruling out lupus than making the diagnosis of lupus. However, a number of features are significantly more frequent in lupus membranous glomerulopathy. Therefore, identification of these features, especially more than one, warrants a high suspicion of lupus rather than nonlupus membranous glomerulopathy even in patients without clinically overt systemic lupus erythematosus. The positive/negative predictive values of some of the pathologic features studied are as follows: mesangial dense deposits 63/99, subendothelial dense deposits 77/93, tubuloreticular inclusions 61/96, intense C1q deposition 47/95, tubular basement membrane deposits 100/87, and glomerular hypercellularity 26/86.Différentiation pathologique entre glomérulopathie extra-membraneuse lupique et non lupique. Les caractéristiques cliniques et pathologiques suivantes ont été évaluées chez 170 malades atteints de glomérulopathie extra-membraneuse documentée par microscopie électronique: l'âge, le sexe, la race, les critères de lupus de l'American Rheumatism Association, les ANA sériques, le complément sérique, l'hypercellularité glomérulaire, le stade des dépôts denses sous-épithéliaux, les inclusions endothéliales tubuloréticulaires, les dépôts dans la membrane basale tubulaire, les ANA tissulaires, les dépôts glomérulaires d'IgG, IgM, IgA, C3, C4, et C1q. Au moment de la biopsie, 148 malades n'avaient pas d'argument clinique pour un lupus, et 22 avaient un diagnostic clinique de lupus. Six malades supplémentaires ont développé un lupus patent après une moyenne de 12 mois. L'incidence des caractéristiques sérologiques et pathologiques dans la glomérulopathie extra-membraneuse lupique ou non lupique a été déterminée. Ces données ont été utilisées pour calculer la sensibilité, la spécificité, les valeurs prédictives positives et négatives, et l'efficacité globale de chaque paramètre pour différencier entre glomérulopathie extra-membraneuse lupique ou non lupique. D'une façon générale, les caractéristiques sérologiques, morphologiques et immunohistopathologiques sont plus puissantes pour éliminer le lupus que pour faire le diagnostic de lupus. Cependant, un certain nombre de caractéristiques sont significativement plus fréquentes dans la glomérulopathie extra-membraneuse lupique. C'est pourquoi la mise en évidence de ces caractéristiques, surtout s'il y en a plus d'une, apporte une forte suspicion de glomérulopathie extra-membraneuse plus lupique que non lupique, même chez des malades sans lupus erythémateux disséminé cliniquement patent. Les valeurs prédictives positives/négatives de certaines des caractéristiques pathologiques étudiées sont les suivantes: dépôts denses mésangiaux 63/99, dépôts denses sous-endothéliaux 77/93, inclusions tubuloréticulaires 61/96, dépôts intenses de C1q 47/95, dépôts dans la membrane basale tubulaire 100/87, et hypercellularité glomérulaire 26/86

Chemistry of Advanced Materials 3(2) (2018) 36-59 Antioxidant, Anti-inflammatory and Neuroprotective Activities of a Plant Extract Derived from Traditional Chinese Medicine: SuHeXiang Wan (AT000)

International audienceIn this paper, we present SuHeXiang Wan, a medicine used in traditional Chinese medicine for the treatment of epilepsy and convulsions. We investigated the antioxidant, anti-inflammatory and neuroprotective activities of the same treatment designated as AT000. The synergy of the two plants, Dryobalanops aromatica and Saussurea lappa, of which the use in alimentary supplements is considered controversial, was evaluated for the first time. The antioxidant activity of the extract was assessed by DPPH and ORAC tests while the anti-inflammatory activity was determined by measuring the capacity of macrophages to generate a strong inflammatory response when stimulated with antigens, inducing NO release. The extract efficacy on the attenuation of the Aβ25-35-induced learning deficits (spatial working memory: spontaneous alternation in the Y-maze and contextual long-term memory: passive avoidance test) was evaluated in vivo in mice seven days after the peptide administration. The impact on lipid peroxidation in the hippocampus, an index of oxidative Chemistry of Advanced Materials (CAM) Journal homepage: http://issrpublishing.com/cam/ Iskandar et al., Chemistry of Advanced Materials 3(2) (2018) 36-59 37 stress, was also evaluated. AT000 extract showed a strong antioxidant activity at 2 mg/mL, 10 mg/mL and 301774 Trolox equivalents according to the DPPH and ORAC tests respectively. The 21-days AT000 treatment dose-dependently alleviated Aβ25-35-induced deficits, with significant prevention at the highest dose tested (250 mg/Kg/day) on the spontaneous alternation, step-through latency and escape latency parameter. 21-days AT000 treatment dose-dependently attenuated also Aβ25-35-induced increase lipid peroxidation, with a significant and complete blockade at the highest doses tested. Synergistic experiments showed that the presence of Dryobalanops aromatica and Saussurea lappa is crucial to obtain a neuroprotective effect. According to these results, AT000 could be a candidate compound in the development of therapeutic drugs for the prevention and treatment of Alzheimer's disease

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Development of innovative vectorizable forms in the context of age-related diseases

La maladie d'Alzheimer est une maladie dégénérative du cerveau où s'accumulent des substances chimiques anormales responsables d'une détérioration progressive de la mémoire et des capacités intellectuelles. C'est une maladie neuro dégénérative qui provoque des lésions dans le cerveau. Les lésions irréversibles conduisent à un déclin des fonctions cognitives, qui servent à traiter l’information, et comportementales au fur et à mesure de la progression de la maladie. Pertes de mémoire immédiate, puis des souvenirs plus anciens, modifications du jugement et du raisonnement, changements d'humeur et de comportement en sont les principales manifestations.Contrairement à une idée reçue, la maladie d'Alzheimer n'est pas liée au vieillissement normal du cerveau. Aujourd’hui, le coût de la maladie en Europe est estimé à 160 Millions d’euros/an, malgré ça, il n’y a pas de traitement symptomatique efficace.Les nouvelles approches non médicamenteuses doivent être explorées afin de ralentir la progression de la maladie. La recherche dans le domaine du « Drug Delivery System » révèle des systèmes de plus en plus prometteurs. L’adressage de molécules d’intérêt thérapeutique vers un tissu cible est un défi de taille à rechercher en matière de « Drug Delivery ». De nouvelles technologies de ciblage sont apparues. La recherche de vecteurs ayant une durée de vie suffisamment longue dans le corps pour atteindre la zone cible a déjà été mise en place. Ce travail constitue un pas modeste dans l’exploration de la phytothérapie nanovectorisée pour le traitement de la maladie d’Alzheimer.Alzheimer's disease is a degenerative brain disease where abnormal chemicals accumulate causing progressive deterioration of memory and intellectual ability. It is a neurodegenerative disease that causes lesions in the brain. Irreversible lesions lead to a decline in cognitive functions, which serve to process information, and behavioral as the disease progresses. Loss of immediate memory, and then older memories, changes in judgment and reasoning, changes in mood and behavior are the main manifestations.Contrary to popular belief, Alzheimer's disease is not related to the normal aging of the brain. Today, the cost of the disease in Europe is estimated at 160 million euros/year, despite that, there is no effective symptomatic treatment.New non-drug approaches should be explored to slow the progression of the disease. Research in the field of the "Drug Delivery System" reveals increasingly promising systems. Addressing molecules of therapeutic interest to a target tissue is a major challenge in Drug Delivery. New targeting technologies have emerged. The search for vectors having a sufficiently long life in the body to reach the target area has already been put in place. This work is a modest step in the exploration of nanovectorized herbal medicine for the treatment of Alzheimer's disease

Antioxidant, Anti-inflammatory and Neuroprotective Activities of a Plant Extract Derived from Traditional Chinese Medicine SuHeXiang Wan (AT000)

International audienceIn this paper, we present SuHeXiang Wan, a medicine used in traditional Chinese medicine for the treatment of epilepsy and convulsions. We investigated the antioxidant, anti-inflammatory and neuroprotective activities of the same treatment designated as AT000. The synergy of the two plants, Dryobalanops aromatica and Saussurea lappa, of which the use in alimentary supplements is considered controversial, was evaluated for the first time. The antioxidant activity of the extract was assessed by DPPH and ORAC tests while the anti-inflammatory activity was determined by measuring the capacity of macrophages to generate a strong inflammatory response when stimulated with antigens, inducing NO release. The extract efficacy on the attenuation of the Aβ25-35-induced learning deficits (spatial working memory: spontaneous alternation in the Y-maze and contextual long-term memory: passive avoidance test) was evaluated in vivo in mice seven days after the peptide administration. The impact on lipid peroxidation in the hippocampus, an index of oxidative Chemistry of Advanced Materials (CAM) Journal homepage: http://issrpublishing.com/cam/ Iskandar et al., Chemistry of Advanced Materials 3(2) (2018) 36-59 37 stress, was also evaluated. AT000 extract showed a strong antioxidant activity at 2 mg/mL, 10 mg/mL and 301774 Trolox equivalents according to the DPPH and ORAC tests respectively. The 21-days AT000 treatment dose-dependently alleviated Aβ25-35-induced deficits, with significant prevention at the highest dose tested (250 mg/Kg/day) on the spontaneous alternation, step-through latency and escape latency parameter. 21-days AT000 treatment dose-dependently attenuated also Aβ25-35-induced increase lipid peroxidation, with a significant and complete blockade at the highest doses tested. Synergistic experiments showed that the presence of Dryobalanops aromatica and Saussurea lappa is crucial to obtain a neuroprotective effect. According to these results, AT000 could be a candidate compound in the development of therapeutic drugs for the prevention and treatment of Alzheimer's disease

Dialium guineense Willd. Parkia biglobosa (Jacq.) R. Br. Ex Benth. and Tamarindus indica L.: Review of known and synergetic bioactive compounds

International audienceNative from Africa, Dialium guineense Willd. Parkia biglobosa R. Br. Ex Benth. And Tamarindus indica L. grow in tropical regions, and are very widespread in West Africa, particularly in Benin. They are simultaneously used in the traditional healing of infectious diseases but there is a lack on their bioactive compounds description. This work places a special emphasis on inventory of known bioactives compounds from the three plants and their mechanism of action in order to identify the need for further research. It emerges from this work that numerous studies confirm the biological activities of the plants extracts. Nevertheless, few bioactive molecules are described as well as the mode of action of the active extracts