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Appropriate disposal of dead farming animals is required to guarantee effective disease control while protecting the environment. In crisis situations, alternatives to rendering can be used, including on-farm burial. The objectives of this study were to: (i) describe the burial and monitoring protocols used on poultry farms in France in response to major avian influenza outbreaks; (ii) assess the effectiveness of the burial protocol, in terms of both technical and biosecurity aspects, and microbiological, physical and chemical changes of the buried materials and the environment over time; (iii) provide recommendations for future burial and follow-up protocols. Five on-farm burial sites were monitored between March 2022 and March 2023, with at least four visits per farm. In addition to visual observations, soil, leachate, air and drilling water samples were collected, as well as boot swabs on/near the pit or on carcasses. For all five farms, microbiological analyses were performed to detect avian influenza virus (AIV), Clostridium botulinum and Salmonella spp. At one site, sampled drilling water was analysed to describe its physical and chemical properties. Visual anomalies were found at the sites over time, such as subsidence of the pits, presence of traces of wild and domestic animals, and rising to the surface of pieces of carcasses and feathers. AIV RNA was detected at all burial sites and in 4 % (8/201) of the collected samples. Viral genome was found up to nine months after burial on one farm. Clostridium botulinum was detected in 16 % (19/117) of the samples, whereas all samples tested negative for Salmonella spp. (0/109) at all sites and at all sampling points. All drilling water samples were compliant with drinking water standards. Our assessments demonstrated how the burial pits changed over time and the need to monitor them regularly so that corrective measures can be taken, if needed. In conclusion, our study can be used as a baseline for preparing better burial and follow-up protocols for future crisis situations. We recommend to standardise trench size and depth, to add mounding soil to the top of the pit and to set up a fence around. Proper pre-planning in peacetime will make it easier to meet the challenges associated with the management of repeated, high-frequency crises or crises of a new nature., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Inc.)

Background: Researchers have increasingly recognized the importance of structural and social determinants of health (SSDOH) as key drivers of a multitude of diseases and health outcomes. The Multi-Ethnic Study of Atherosclerosis (MESA) is an ongoing, longitudinal cohort study of subclinical cardiovascular disease (CVD) that has followed geographically and racially/ethnically diverse participants starting in 2000. Since its inception, MESA has incorporated numerous SSDOH assessments and instruments to study in relation to CVD and aging outcomes. In this paper, we describe the SSDOH data available in MESA, systematically review published papers using MESA that were focused on SSDOH and provide a roadmap for future SSDOH-related studies., Methods and Findings: The study team reviewed all published papers using MESA data (n = 2,125) through January 23, 2023. Two individuals systematically reviewed titles, abstracts, and full text to determine the final number of papers (n = 431) that focused on at least one SSDOH variable as an exposure, outcome, or stratifying/effect modifier variable of main interest (discrepancies resolved by a third individual). Fifty-seven percent of the papers focused on racialized/ethnic groups or other macrosocial/structural factors (e.g., segregation), 16% focused on individual-level inequalities (e.g. income), 14% focused on the built environment (e.g., walking destinations), 10% focused on social context (e.g., neighborhood socioeconomic status), 34% focused on stressors (e.g., discrimination, air pollution), and 4% focused on social support/integration (e.g., social participation). Forty-seven (11%) of the papers combined MESA with other cohorts for cross-cohort comparisons and replication/validation (e.g., validating algorithms)., Conclusions: Overall, MESA has made significant contributions to the field and the published literature, with 20% of its published papers focused on SSDOH. Future SSDOH studies using MESA would benefit by using recently added instruments/data (e.g., early life educational quality), linking SSDOH to biomarkers to determine underlying causal mechanisms linking SSDOH to CVD and aging outcomes, and by focusing on intersectionality, understudied SSDOH (i.e., social support, social context), and understudied outcomes in relation to SSDOH (i.e., sleep, respiratory health, cognition/dementia)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Besser et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Tuberculosis is a leading cause of death worldwide, and food insecurity is known to negatively influence health outcomes through multiple pathways. Few studies have interrogated the relationship between food insecurity and tuberculosis outcomes, particularly independent of nutrition., Methods: We conducted a prospective cohort study of adults initiating first-line treatment for clinically suspected or microbiologically confirmed drug-sensitive tuberculosis at a rural referral center in Haiti. We administered a baseline questionnaire, collected clinical data, and analyzed laboratory samples. We used logistic regression models to estimate the relationship between household food insecurity (Household Hunger Scale) and treatment failure or death. We accounted for exclusion of patients lost to follow-up using inverse probability of censoring weighting and adjusted for measured confounders and nutritional status using inverse probability of treatment weighting., Results: We enrolled 257 participants (37% female) between May 2020 and March 2023 with a median age (interquartile range) of 35 (25-45) years. Of these, 105 (41%) had no hunger in the household, 104 (40%) had moderate hunger in the household, and 48 (19%) had severe hunger in the household. Eleven participants (4%) died, and 6 (3%) had treatment failure. After adjustment, food insecurity was significantly associated with subsequent treatment failure or death (odds ratio 5.78 [95% confidence interval, 1.20-27.8]; P = .03)., Conclusions: Household food insecurity at tuberculosis treatment initiation was significantly associated with death or treatment failure after accounting for loss to follow-up, measured confounders, and nutritional status. In addition to the known importance of undernutrition, our findings indicate that food insecurity independently affects tuberculosis treatment outcomes in Haiti., Competing Interests: Potential conflicts of interest . The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Acute ischemic stroke (AIS) is an immediate emergency whose management is becoming more and more personalized while facing a limited number of neurologists with high expertise. Clinical decision support systems (CDSS) are digital tools leveraging information and artificial intelligence technologies. Here, we present the Strokecopilot project, a CDSS for the management of the acute phase of AIS. It has been designed to support the evidence-based medicine reasoning of neurologists regarding the indications of intravenous thrombolysis (IVT) and endovascular treatments (ET)., Methods: Reference populations were manually extracted from the field's main guidelines and randomized clinical trials (RCT). Their characteristics were harmonized in a computerized reference database. We developed a web application whose algorithm identifies the reference populations matching the patient's characteristics. It returns the latter's outcomes in a graphical user interface (GUI), whose design has been driven by real-world practices., Results: Strokecopilot has been released at www.digitalneurology.net . The reference database includes 25 reference populations from 2 guidelines and 15 RCTs. After a request, the reference populations matching the patient characteristics are displayed with a summary and a meta-analysis of their results. The status regarding IVT and ET indications are presented as "in guidelines", "in literature", or "outside literature references". The GUI is updated to provide several levels of explanation. Strokecopilot may be updated as the literature evolves by loading a new version of the reference populations' database., Conclusion: Strokecopilot is a literature-based CDSS, developed to support neurologists in the management of the acute phase of AIS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

While some follicular lymphoma (FL) patients do not require treatment or experience prolonged responses, others relapse early, and little is known about genetic alterations specific to patients with a particular clinical behavior. We selected 56 grade 1-3A FL patients according to their need of treatment or timing of relapse: never treated (n = 7), non-relapsed (19), late relapse (14), early relapse or POD24 (11), and primary refractory (5). We analyzed 56 diagnostic and 12 paired relapse lymphoid tissue biopsies and performed copy number alteration (CNA) analysis and next generation sequencing (NGS). We identified six focal driver losses (1p36.32, 6p21.32, 6q14.1, 6q23.3, 9p21.3, 10q23.33) and 1p36.33 copy-neutral loss of heterozygosity (CN-LOH). By integrating CNA and NGS results, the most frequently altered genes/regions were KMT2D (79%), CREBBP (67%), TNFRSF14 (46%) and BCL2 (40%). Although we found that mutations in PIM1, FOXO1 and TMEM30A were associated with an adverse clinical behavior, definitive conclusions cannot be drawn, due to the small sample size. We identified common precursor cells harboring early oncogenic alterations of the KMT2D, CREBBP, TNFRSF14 and EP300 genes and 16p13.3-p13.2 CN-LOH. Finally, we established the functional consequences of mutations by means of protein modeling (CD79B, PLCG2, PIM1, MCL1 and IRF8). These data expand the knowledge on the genomics behind the heterogeneous FL population and, upon replication in larger cohorts, could contribute to risk stratification and the development of targeted therapies., (© 2023 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

We detected highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus in a domestic cat that lived near a duck farm infected by a closely related virus in France during December 2022. Enhanced surveillance of symptomatic domestic carnivores in contact with infected birds is recommended to prevent further spread to mammals and humans.

Introduction: Currently, bladder cancer detection is based on cytology and cystoscopy. White light cystoscopy (WLC) is an invasive procedure and may under-detect flat lesions. Blue light cystoscopy (BLC) and narrow band imaging (NBI) cystoscopy are new modalities that could improve the detection of non-muscle invasive bladder cancer (NMIBC) and its recurrence or progression to muscle invasive bladder cancer. We present a systematic review on BLC and NBI cystoscopy for bladder cancer diagnosis and NMIBC follow-up., Material and Methods: All available systematic reviews and meta-analyses on cystoscopy published in PubMed® between May 2010 and March 2021 were identified and reviewed. The main endpoints were clinical performance for bladder cancer diagnosis and for recurrence or progression detection during NMIBC follow-up, and additional value compared with cytology and/or WLC., Results: Most of the meta-analyses and systematic reviews published suggest a better sensitivity of BLC and NBI cystoscopy compared to WLC, particularly for the detection of flat lesions (CIS). NBI- and BLC-guided TURBT could decrease the recurrence rates. However, their clinical utility to reduce progression rate and increase survival is still unclear., Conclusions: BLC and NBI cystoscopy are efficient techniques for bladder cancer diagnosis and NMIBC follow-up. However, their clinical benefit remains to be confirmed., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Bladder cancer detection and follow-up is based on cystoscopy and/or cytology, but it remains imperfect and invasive. Current research focuses on diagnostic biomarkers that could improve bladder cancer detection and follow-up by discriminating patients at risk of aggressive cancer who need confirmatory TURBT (Transurethral Resection of Bladder Tumour) from patients at no risk of aggressive cancer who could be spared from useless explorations., Objective: To perform a systematic review of data on the clinical validity and clinical utility of eleven urinary biomarkers (VisioCyt ® , Xpert ® Bladder, BTA stat ® , BTA TRAK™, NMP22 BC ® , NMP22 ® BladderChek ® Test, ImmunoCyt™/uCyt1+™, UroVysion Bladder Cancer Kit ® , Cxbladder, ADXBLADDER, Urodiag ® ) for bladder cancer diagnosis and for non-muscle invasive bladder cancer (NMIBC) follow-up., Methods: All available studies on the 11 biomarkers published between May 2010 and March 2021 and present in MEDLINE ® were reviewed. The main endpoints were clinical performance for bladder cancer detection, recurrence or progression during NMIBC monitoring, and additional value compared to cytology and/or cystoscopy., Results: Most studies on urinary biomarkers had a prospective design and high level of evidence. However, their results should be interpreted with caution given the heterogeneity among studies. Most of the biomarkers under study displayed higher detection sensitivity compared with cytology, but lower specificity. Some biomarkers may have clinical utility for NMIBC surveillance in patients with negative or equivocal cystoscopy or negative or atypical urinary cytology findings, and also for recurrence prediction., Conclusion: Urinary biomarkers might have a complementary place in bladder cancer diagnosis and NMIBC surveillance. However, their clinical benefit remains to be confirmed., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In France during winter 2016-2017, 487 outbreaks of clade 2.3.4.4b H5N8 subtype high pathogenicity (HP) avian influenza A virus (AIV) infections were detected in poultry and captive birds. During this epizootic, HPAIV A/decoy duck/France/161105a/2016 (H5N8) was isolated and characterized in an experimental infection transmission model in conventional mule ducks. To investigate options to possibly protect such ducks against this HPAIV, three vaccines were evaluated in controlled conditions. The first experimental vaccine was derived from the hemagglutinin gene of another clade 2.3.4.4b A(H5N8) HPAIV. It was injected at three weeks of age, either alone (Vac1) or after a primer injection at day-old (Vac1 + boost). The second vaccine (Vac2) was a commercial bivalent adjuvanted vaccine containing an expressed hemagglutinin modified from a clade 2.3.2 A(H5N1) HPAIV. Vac2 was administered as a single injection at two weeks of age. The third experimental vaccine (Vac3) also incorporated a homologous 2.3.4.4b H5 HA gene and was administered as a single injection at three weeks of age. Ducks were challenged with HPAIV A/decoy duck/France/161105a/2016 (H5N8) at six weeks of age. Post-challenge virus excretion was monitored in vaccinated and control birds every 2-3 days for two weeks using real-time reverse-transcription polymerase chain reaction and serological analyses (haemagglutination inhibition test against H5N8, H5 ELISA and AIV ELISA) were performed. Vac1 abolished oropharyngeal and cloacal shedding to almost undetectable levels, whereas Vac3 abolished cloacal shedding only (while partially reducing respiratory shedding) and Vac2 only partly reduced the respiratory and intestinal excretion of the challenge virus. These results provided relevant insights in the immunogenicity of recombinant H5 vaccines in mule ducks, a rarely investigated hybrid between Pekin and Muscovy duck species that has played a critical role in the recent H5 HPAI epizootics in France., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

During winter 2020-2021, France and other European countries were severely affected by highly pathogenic avian influenza H5 viruses of the Gs/GD/96 lineage, clade 2.3.4.4b. In total, 519 cases occurred, mainly in domestic waterfowl farms in Southwestern France. Analysis of viral genomic sequences indicated that 3 subtypes of HPAI H5 viruses were detected (H5N1, H5N3, H5N8), but most French viruses belonged to the H5N8 subtype genotype A, as Europe. Phylogenetic analyses of HPAI H5N8 viruses revealed that the French sequences were distributed in 9 genogroups, suggesting 9 independent introductions of H5N8 from wild birds, in addition to the 2 introductions of H5N1 and H5N3., (© 2022 The Authors. Transboundary and Emerging Diseases published by Wiley-VCH GmbH.)

An H3N1 avian influenza virus was detected in a laying hens farm in May 2019 which had experienced 25% mortality in Northern France. The complete sequencing of this virus showed that all segment sequences belonged to the Eurasian lineage and were phylogenetically very close to many of the Belgian H3N1 viruses detected in 2019. The French virus presented two genetic particularities with NA and NS deletions that could be related to virus adaptation from wild to domestic birds and could increase virulence, respectively. Molecular data of H3N1 viruses suggest that these two deletions occurred at two different times., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Microbiological diagnosis of bloodstream infection (BSI) is made several hours after blood culture sampling. This delay could be critical in ambulatory clinics, emergency departments, and hospital day care units, as the patient may be discharged prior to blood culture positivity. Our aim was to evaluate the clinical outcome (including the number of readmissions) of patients diagnosed with BSI after discharge. We prospectively included all adult patients with positive blood culture for BSI that was confirmed after discharge from our center (Grenoble-Alpes University Hospital) in 2016. Patients were contacted about their blood culture results, and their clinical status was controlled via an external consultation or their family physician, with hospital readmission if necessary. Clinical outcome, accuracy of initial diagnosis, microbiological epidemiology, and antibiotic prescription were assessed. In 2016, 1433 episodes of positive blood culture were detected in our hospital, with 50 (3.5%) occurring after patient discharge. Clinically relevant bacteria were determined in 32/50 cases (64%), while other positive blood culture results were considered to be contaminants. Clinical reevaluation was performed in 45 patients (90%). The diagnosis was changed during the clinical reassessment of 24/49 patients (49%). Antibiotics were prescribed prior to discharge for 24/50 patients (48%), modified during follow-up for 15/45 (33%), and initiated for 13/45 (29%) at the reevaluation. Overall, 24/45 (53%) patients were readmitted to hospital units after reevaluation. The clinical follow-up of patients with positive blood culture after discharge led to diagnostic changes and hospital readmission in around half of patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In 2021, France faced large avian influenza outbreaks, like in 2016 and 2017. Controlling these outbreaks required the preventive depopulation of a large number of duck farms. A previous study in 2017 showed that the quality of decontamination of trucks and transport crates used for depopulation was often insufficient. A new study was then set up to evaluate cleaning and disinfection (C&D) of trucks and crates used for duck depopulation and whether practices had changed since 2017. Three methods were used to assess decontamination: 1) detection of avian influenza virus (AIV) genome, 2) visual inspection of cleanliness, and 3) microbial counts, considering that 2 and 3 are commonly used in abattoirs. Another objective of the study was to evaluate the correlation between results obtained with the 3 methods. In 5 abattoirs, 8 trucks and their crates were sampled by swabbing to detect AIV genome by rRT-PCR before and after decontamination. Visual cleanliness scores and coliform counts were also determined on crates after C&D. Trucks and crates were decontaminated according to the abattoirs' protocols. Before C&D, 3 quarters of crates (59/79) and 7 of 8 trucks were positive for AIV genome. C&D procedures were reinforced in 2021 compared to 2017; use of detergent solution and warm water were more common. Nevertheless, 28% of the crates were positive for AIV genome after C&D, despite the fact that cleaning scores and microbiological counts were satisfactory for 84% and 91% of the crates, respectively. No correlation was observed between results for AIV genome detection and results from visual control or from coliform counts. Abattoirs are encouraged to use environmental sampling coupled with AIV genome detection to monitor the quality of cleaning and disinfection of trucks and crates during AI outbreaks. Reinforcement of biosecurity measures at abattoirs is still needed to avoid residual contamination of the equipment and cross-contamination during the decontamination process., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

FOXL2 somatic mutation occurs in a high percentage of ovarian adult granulosa cell tumors and DICER1 mutations in a high proportion of Sertoli-Leydig cell tumors. These mutations have only been studied in a limited number of juvenile granulosa cell tumors (JGCTs), and their occurrence and frequency in these neoplasms is controversial. We aimed to determine the frequency of FOXL2 and DICER1 mutations in a large cohort of 50 JGCTs, and to evaluate the prognostic impact of these mutations. A FOXL2 hotspot mutation was found in 2/50 JGCTs. Review of these 2 cases reclassified them as adult granulosa cell tumors. Thus, FOXL2 mutation was absent from our large cohort of JGCTs. DICER1 mutations in the RNase IIIb domain were found in 4 cases. After review of the mutated cases, 1 was reclassified as a gynandroblastoma with a prominent JGCT component. Thus, DICER1 mutations were detected in 3/47 (6%) of pathologically confirmed JGCTs. Our results show that FOXL2 mutations are not present in JGCT, whereas a small percentage of these neoplasms exhibit DICER1 mutations., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Molecular rapid diagnostic assays associated with antimicrobial stewardship have proven effective for the early adaptation of empiric therapy in bloodstream infections. The ePlex ® BCID (GenMark Diagnostics) Panels allow identification of 56 bacteria and fungi and 10 resistance genes in 90 min directly from positive blood cultures. We prospectively evaluated 187 sepsis episodes at Grenoble University Hospital and retrospectively analyzed the cases to measure the potential clinical impact of the ePlex BCID results. Identification of all pathogens was obtained for 164/187 (88%) bloodstream infections with 100% detection of antimicrobial resistance genes (17 bla CTX-M , 1 vanA , and 17 mecA genes). Only 15/209 (7%) strains were not covered by the panels. Sensitivity for detection of micro-organisms targeted by the RUO BCID-GP, BCID-GN, and BCID-FP Panels was respectively 84/84 (100%), 103/107 (96%), and 14/14 (100%). Interestingly, accurate identification of all pathogens was achieved in 15/17 (88%) polymicrobial samples. Retrospective analysis of medical records showed that a modification of antimicrobial treatment would have been done in 45% of the patients. Treatment modifications would have been an optimization of empiric therapy, a de-escalation or an escalation in respectively 16, 17, and 11% of the patients. Moreover, 11% of the samples were classified as contaminants or not clinically relevant and would have led to early de-escalation or withdrawal of any antibiotic. Detection of resistance genes in addition to identification alone increased escalation rate from 4 to 11% of the patients. Absence of the ePlex result was considered a lost opportunity for therapy modification in 28% of patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Bryant, Almahmoud, Pierre, Bardet, Touati, Maubon, Cornet, Richarme, Maurin, Pavese and Caspar.)

Background: Depression, anxiety, and cognitive impairments occur in up to 40 % of adults with AF and are associated with poorer health-related quality of life (HRQoL) and higher symptom burden. However, it is unknown how often these impairments co-occur, or multimorbidity, and how multimorbidity effects HRQoL and symptom burden., Methods: Patients with AF age ≥65 years with a CHA 2 DS 2 VASC risk score ≥ 2 and eligible for oral anticoagulation therapy were recruited from five clinics in a prospective cohort study. Participants completed validated measures of depression (PHQ9) and anxiety (GAD7), cognitive impairment (MoCA), and HRQOL and AF symptom burden (AFEQT). Multinomial logistic regression was used., Results: Participants (N = 1244, 49 % female) were on average 76 ± 7 years; 86 % were non-Hispanic white. Approximately 35 % of participants had 1 impairment, 17 % had 2 impairments and 8% had 3 impairments; 39 % had none of the 3 impairments examined. Compared to participants with no impairments, patients with 1, 2 and 3 impairments had higher odds of poor HRQoL (adjusted OR [AOR] = 1.77, 95 % CI 1.21, 2.60; AOR = 6.64, 95 % CI 4.43, 9.96; and AOR = 7.50, 95 % CI 4.40, 12.77, respectively) and those with 2 and 3 impairments had higher odds of high symptom burden (AOR = 3.69 95 % CI 2.22, 6.13; and AOR = 5.41 95 % CI 2.85, 10.26)., Conclusions: Psychosocial/cognitive multimorbidity is common among older adults with AF and is associated with poor HRQoL and high symptom burden. Clinicians might consider incorporating psychosocial and cognitive screens into routine care as this may identify a high-risk population., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Dimethyl fumarate (DMF) and its active metabolite monomethyl fumarate (MMF) effectively lead to reduction in disease relapses and active magnetic resonance imaging (MRI) lesions. DMF and MMF are known to be effective in modulating T- and B-cell responses; however, their effect on the phenotype and function of human myeloid dendritic cells (mDCs) is not fully understood., Objective: To investigate the role of MMF on human mDCs maturation and function., Methods: mDCs from healthy controls were isolated and cultured in vitro with MMF. The effect of MMF on mDC gene expression was determined by polymerase chain reaction (PCR) array after in vitro MMF treatment. The ability of mDCs to activate T cells was assessed by in vitro co-culture system. mDCs from DMF-treated multiple sclerosis (MS) patients were analyzed by flow cytometry and PCR., Results: MMF treatment induced a less mature phenotype of mDCs with reduced expression of major histocompatibility complex class II (MHC-II), co-stimulatory molecules CD86, CD40, CD83, and expression of nuclear factor κB (NF-κB) subunits RELA and RELB. mDCs from DMF-treated MS patients also showed the same immature phenotype. T cells co-cultured with MMF-treated mDCs showed reduced proliferation with decreased production of interferon gamma (IFN-γ), interleukin-17 (IL-17), and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to untreated cells., Conclusion: We report that MMF can modulate immune response by affecting human mDC function.

Background: Outcome of patients with mutation of the FLT3 tyrosine kinase domain (FLT3-TKD) in acute myeloid leukemia (AML) remains controversial., Patients and Methods: Herein, we present a retrospective study of 126 newly diagnosed patients with AML performed in 2 French centers., Results: FLT3-TKD mutations represented 12.7% of patients, whereas FLT3-internal tandem duplication (ITD) mutation was observed in 20.6% of AML cases and 1.6% of patients harbored both anomalies. At diagnosis, FLT3-TKD and FLT3-ITD were associated with higher peripheral leukocytes count and a higher blast count in bone marrow (P < 10 -4 ). Mutations of the NPM1 gene were frequently associated to FLT3-TKD (68.7%) and FLT3-ITD (61.5%) mutations compared with FLT3 wild type (WT) patients (P < 10 -4 ). Patients with both FLT3-TKD and NPM1 mutations (n = 12; 9.5%) showed a favorable outcome. Interestingly, mutations in NPM1 gene lost their favorable prognostic when not associated with FLT3-TKD both in univariate and multivariate analyses., Conclusion: Our data suggest that FLT3-TKD mutations should be routinely determined at the time of diagnosis. In association with NPM1 mutations, patients should follow the therapeutic schedule of favorable-risk patients with AML., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is a rare but severe complication. Among 326 patients who underwent TAVI at Grenoble Alpes University Hospital, six (1.8%) cases of IE and 11 (3.4%) cases of bacteraemia were identified. No cases of IE were linked to the intervention; one was due to Staphylococcus aureus despite a screening and targeted decolonization strategy. This underscores the need for randomized studies to evaluate the benefit and cost-effectiveness of this policy., (Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: The prognosis of poorly differentiated thyroid carcinomas (PDTC) is heterogeneous though generally poor. The objectives of this study were to identify clinical and molecular factors of poor prognosis., Methods: One hundred four consecutive patients treated for a PDTC between 01/01/2000 and 31/12/2010 were included in this study. A pathological review was done for all cases (blinded to clinical data and outcome)., Results: All patients underwent thyroidectomy. Adjuvant radioactive-iodine was administered in 95.2% of them. Tumours were pT3 or pT4 in 68.3% of cases and metastatic in 38.5% of patients. Extrathyroidal extension (ETE) was observed in 40% of patients. At the end of the initial treatment, only 37% of patients were considered in remission. Fifty-two patients (50%) became refractory to radioiodine during follow-up. The 5-year overall survival was 72.8% and the 5-year recurrence-free survival (RFS) was 45.3%. Remission after initial treatment was an independent factor of RFS (HR = 0.22; [0.10-0.49]). ETE was the only significant parameter influencing the overall survival in multivariate analysis. TERT promoter mutations at positions -124 (C228T) and -146 (C250T) were present in 38.1% of analysed patients and significantly associated with radioiodine resistance but not with overall survival. Half of TERT promoter mutant tumours harboured also RAS or BRAF mutations., Conclusion: PDTC form a heterogeneous group of patients with usual late-stage diagnosis, low radioactive iodine avidity and frequent metastatic spread. TERT promoter mutations could help to identify patients with high risk of radio-iodine refractoriness., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Azacitidine inhibits DNA methyltransferases, including DNMT1, and is currently the standard of care for patients with higher-risk myelodysplastic syndrome (HRMDS) or low blast count acute myeloid leukemia (AML). Experimental Design: The expression of 754 miRNAs was compared in azacitidine-resistant and azacitidine-sensitive myelodysplastic syndrome cells. We investigated the role of differentially expressed miRNAs on DNMT1 expression and azacitidine resistance in vitro We next evaluated anti-DNMT1 miRNA expression in pretreatment bone marrow samples derived from 75 patients treated with azacitidine for HRMDS or AML. Results: Seven miRNAs, including 5 that in silico targeted the DNMT1 3' UTR, were repressed in azacitidine-resistant cells in which DNMT1 protein levels were significantly higher. Ectopic anti-DNMT1 miRNA expression decreased DNMT1 expression and increased azacitidine sensitivity, whereas specific inhibition of endogenous anti-DNMT1 miRNAs increased DNMT1 expression and triggered azacitidine resistance. In patients treated with azacitidine, decreased expression of anti-DNMT1 miRNAs was associated with poor outcome. miR-126* had the strongest prognostic impact. Patients with miR-126* low myelodysplastic syndrome had significantly lower response rates ( P = 0.04) and higher relapse rates ( P = 0.03), as well as shorter progression-free (PFS; P = 0.004) and overall survival (OS; P = 0.004). Multivariate analysis showed that age, miR-126* expression, and revised International Prognostic Scoring System risk independently predicted PFS and OS. In 15 patient samples collected over time, decreased miRNA expression levels were associated with secondary resistance. Conclusions: A decreased expression of anti-DNMT1 miRNAs might account for azacitidine resistance in HRMDS and AML, and measuring miRNA expression before and during treatment might help predict primary or secondary azacitidine resistance. Clin Cancer Res; 23(12); 3025-34. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Background: Controlling antibiotic use in healthcare establishments limits their consumption and the emergence of bacterial resistance., Aim: To evaluate the efficiency of an innovative antibiotic stewardship strategy implemented over three years in a university hospital., Methods: An antimicrobial multi-disciplinary team (AMT) [pharmacist, microbiologist and infectious disease specialist (IDS)] conducted a postprescription review. Specific coding of targeted antibiotics (including broad-spectrum β-lactams, glycopeptides, lipopeptides, fluoroquinolones and carbapenems) in the computerized physician order entry allowed recording of all new prescriptions. The data [patient, antibiotic(s), prescription start date, etc.] were registered on an AMT spreadsheet with shared access, where the microbiologist's opinion on the drug choice, based on available microbiology results, was entered. When the microbiologist and pharmacist did not approve the antibiotic prescribed, a same-day alert was generated and sent to the IDS. That alert led the IDS to re-evaluate the treatment., Findings: From 2012 to 2014, 2106 targeted antibiotic prescriptions were reviewed. Among them, 389 (18.5%) generated an alert and 293 (13.9%) were re-evaluated by the IDS. Recommendations (mostly de-escalation or discontinuation) were necessary for 136 (46.4%) and the prescribers' acceptance rate was 97%. The estimated intervention time was <30 min/day for each AMT member. This system allowed correct use of targeted antibiotics for 91.8% of prescriptions, but had no significant impact on targeted antibiotic consumption., Conclusion: This computerized, shared access, antibiotic stewardship strategy seems to be time saving, and effectively limited misuse of broad-spectrum antibiotics., (Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Childhood iron deficiency anemia (IDA) is an important contributor to under-five mortality in the developing world. There is evidence that Community Health Worker (CHW) delivered programs to increase maternal knowledge of child health practices may decrease childhood IDA. This study reports findings on the association between a long standing CHW intervention and childhood anemia status in rural Haiti., Methods: Using structural equations and mediation analyses on data from a household-based survey of 621 mother/child dyads, we tested the hypothesis that CHW would have a direct positive effect on maternal knowledge and an indirect effect on childhood anemia in rural Haiti., Results: CHW contact was significantly associated with maternal knowledge of key child health practices (β = 0.193, SE = 0.058, p  = 0.001). However, knowledge was not associated with childhood anemia (β = -0.008, SE = 0.009, p  = 0.382). Maternal knowledge categories significantly affected by CHW contact included diarrheal prevention knowledge (β = 0.111, SE = 0.045, p  = 0.013) and signs of malnutrition (β = 0.217, SE = 0.071, p  = 0.002). There was no significant association with knowledge of vitamin A and iron rich foods (β = 0.057, SE = 0.032, p  = 0.074), which is the intervention most likely to impact childhood anemia. In all path models tested, we identified the control variables low household socio-economic status, mothers' anemia status, and child's age less than 24 months as significant predictors of childhood anemia., Conclusions: CHWs delivered interventions are associated with improved maternal knowledge of child health practices in rural Haiti; however, this knowledge is not associated with improved childhood anemia. Concurrently with CHW-delivered programs, interventions household poverty are implied to impact childhood health outcomes in resource poor settings.

Introduction: Whether mutation status should be used to guide therapy is an important issue in many cancers. We correlated mutation profile in radioiodine-refractory (RAIR) metastatic thyroid cancers (TCs) with patient outcome and response to tyrosine kinase inhibitors (TKIs), and discussed the results with other published data., Materials and Methods: Outcome in 82 consecutive patients with metastatic RAIR thyroid carcinoma prospectively tested for BRAF, RAS and PI3KCA mutations was retrospectively analyzed, including 55 patients treated with multikinase inhibitors., Results: Papillary thyroid carcinomas (PTCs) were the most frequent histological subtype (54.9 %), followed by poorly differentiated thyroid carcinoma [PDTC] (30.5 %) and follicular thyroid carcinoma [FTC] (14.6 %). A genetic mutation was identified in 23 patients (28 %) and BRAF was the most frequently mutated gene (23 %). Median progression-free survival (PFS) on first-line TKI treatment was 14.6 months (95% CI 9.9-18.4). BRAF mutation positively influenced median PFS, both in the entire TKI-treated cohort (median PFS 34.7 months versus 11.6 months; hazard ratio [HR] 0.29; 95% CI 0.09-0.98; p = 0.03) and in the TKI-treated PTC cohort (n = 22) [log-rank p = 0.086; HR 2.95; 95 % CI 0.81-10.70). However, in TKI-treated patients, PDTC histologic subtype was the only independent prognostic factor for PFS identified in the multivariate analysis (HR 2.36; 95% CI 1.01-5.54; p = 0.048)., Conclusion: Patients with BRAF-mutant PTC had a significantly longer PFS than BRAF wild-type when treated with TKIs. However, due to the small number of BRAF-mutant patients, further investigations are required, especially to understand the potential positive effect of BRAF mutations in RAIR TC patients while having a negative prognostic impact in RAI-sensitive PTC patients.

Objective: To evaluate the impact of computerized provider order entry (CPOE) at the bedside on medical students training., Materials and Methods: We conducted a randomized cross-controlled educational trial on medical students during two clerkship rotations in three departments, assessing the impact of the use of CPOE on their ability to place adequate monitoring and therapeutic orders using a written test before and after each rotation. Students' satisfaction with their practice and the order placement system was surveyed. A multivariate mixed model was used to take individual students and chief resident (CR) effects into account. Factorial analysis was applied on the satisfaction questionnaire to identify dimensions, and scores were compared on these dimensions., Results: Thirty-six students show no better progress (beginning and final test means = 69.87 and 80.98 points out of 176 for the control group, 64.60 and 78.11 for the CPOE group, p = 0.556) during their rotation in either group, even after adjusting for each student and CR, but show a better satisfaction with patient care and greater involvement in the medical team in the CPOE group (p = 0.035*). Both groups have a favorable opinion regarding CPOE as an educational tool, especially because of the order reviewing by the supervisor., Conclusion: This is the first randomized controlled trial assessing the performance of CPOE in both the progress in prescriptions ability and satisfaction of the students. The absence of effect on the medical skills must be weighted by the small time scale and low sample size. However, students are more satisfied when using CPOE rather than usual training.

Objectives: Actinomycosis is a rare disease favored by disruption of the mucosal barrier. In order to investigate the impact of immunosuppression on outcome we analyzed the most severe cases observed in patients hospitalized in three tertiary care centers., Methods: We reviewed all cases of proven invasive actinomycosis occurring over a 12-year period (1997 to 2009) in three teaching hospitals in the Paris area., Results: Thirty-three patients (16 male) were identified as having an invasive actinomycosis requiring hospitalization. The diagnosis was made by microbiological identification in 26 patients, pathological examination in eight patients, and by both methods in one. Twenty patients (61%) were immunocompromised. Actinomycosis localization was abdominal or pelvic in 17 patients, thoracic in 11, cervicofacial in three, and neurological in two. Twenty patients (61%) underwent surgery. All strains were susceptible to amoxicillin. All patients were treated with a beta-lactam antibiotic, for a median length of 82 days. Twenty-eight patients (85%) were considered as cured. Overall mortality at hospital discharge was 21% (7/33). Mortality was higher in immunocompromised patients (7/20; 21%) compared to non-immunocompromised patients (0/13) (p=0.027). However, six of seven deaths were directly related to the underlying disease., Conclusions: Actinomycosis is a cause of severe infection in immunocompromised patients and a surrogate marker of a poor prognosis in this specific population., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The aim of this study was to assess the infectious diseases (ID) wards of tertiary hospitals in France and Turkey for technical capacity, infection control, characteristics of patients, infections, infecting organisms, and therapeutic approaches. This cross-sectional study was carried out on a single day on one of the weekdays of June 17-21, 2013. Overall, 36 ID departments from Turkey (n = 21) and France (n = 15) were involved. On the study day, 273 patients were hospitalized in Turkish and 324 patients were followed in French ID departments. The numbers of patients and beds in the hospitals, and presence of an intensive care unit (ICU) room in the ID ward was not different in both France and Turkey. Bed occupancy in the ID ward, single rooms, and negative pressure rooms were significantly higher in France. The presence of a laboratory inside the ID ward was more common in Turkish ID wards. The configuration of infection control committees, and their qualifications and surveillance types were quite similar in both countries. Although differences existed based on epidemiology, the distribution of infections were uniform on both sides. In Turkey, anti-Gram-positive agents, carbapenems, and tigecycline, and in France, cephalosporins, penicillins, aminoglycosides, and metronidazole were more frequently preferred. Enteric Gram-negatives and hepatitis B and C were more frequent in Turkey, while human immunodeficiency virus (HIV) and streptococci were more common in France (p < 0.05 for all significances). Various differences and similarities existed in France and Turkey in the ID wards. However, the current scene is that ID are managed with high standards in both countries.

Objectives: The aims of our study were to compare in a cohort of 705 patients the diagnostic performance of two tests to detect autoantibodies to cyclic citrullinated peptides (CCP) and to determine whether a bead-based assay within a multiplex flow immunoassay (MFA) can be used instead of an enzyme linked immunosorbent assay (ELISA) technique in routine practice., Design and Methods: Six hundred and thirty patients with rheumatic symptoms and 75 patients with systemic lupus erythematosus (SLE) were tested for anti-CCP autoantibodies using two techniques: ELISA (Inova) and MFA (BioPlex, Bio-Rad)., Results: Using kappa coefficient, there was an excellent agreement between ELISA and MFA when comparing 630 patients with rheumatic symptoms (κ coefficient, 0.82). In this cohort 174 patients were identified as suffering from RA, while 456 patients suffered from other diseases. Sensitivity and specificity values of anti-CCP autoantibodies for RA were 70.7% and 92.3% for ELISA and 64.4% and 92.8% for MFA. The positive and negative predictive values were 77.4% and 89.2% for ELISA and 77.2% and 87.2% for MFA, respectively. There were no differences in the diagnostic performances between the two assays (Z=0.67). The specificity values of anti-CCP autoantibodies analysing patients with SLE were 97.3% with MFA and 96% with ELISA with an excellent agreement between the methods (98.7%; κ coefficient, 0.79)., Conclusion: Concordance between ELISA and MFA is high in routine practice. Overall, MFA is a powerful tool for rapid assessment of anti-CCP autoantibodies and can replace the ELISA technique, which could be used as a second-line test in some cases., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

EU annual serosurveillance programs show that domestic duck flocks have the highest seroprevalence of H5 antibodies, demonstrating the circulation of notifiable avian influenza virus (AIV) according to OIE, likely low pathogenic (LP). Therefore, transmission characteristics of LPAIV within these flocks can help to understand virus circulation and possible risk of propagation. This study aimed at estimating transmission parameters of four H5 LPAIV (three field strains from French poultry and decoy ducks, and one clonal reverse-genetics strain derived from one of the former), using a SIR model to analyze data from experimental infections in SPF Muscovy ducks. The design was set up to accommodate rearing on wood shavings with a low density of 1.6 ducks/m(2): 10 inoculated ducks were housed together with 15 contact-exposed ducks. Infection was monitored by RNA detection on oropharyngeal and cloacal swabs using real-time RT-PCR with a cutoff corresponding to 2-7 EID50. Depending on the strain, the basic reproduction number (R0) varied from 5.5 to 42.7, confirming LPAIV could easily be transmitted to susceptible Muscovy ducks. The lowest R0 estimate was obtained for a H5N3 field strain, due to lower values of transmission rate and duration of infectious period, whereas reverse-genetics derived H5N1 strain had the highest R0. Frequency and intensity of clinical signs were also variable between strains, but apparently not associated with longer infectious periods. Further comparisons of quantitative transmission parameters may help to identify relevant viral genetic markers for early detection of potentially more virulent strains during surveillance of LPAIV., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: The treatment of recurrent furunculosis is poorly documented and represents a public health challenge. The medical care of this disease is often disappointing, especially as the disease evolution is uncertain and relapses occur. We report the efficacy and safety of our CMC regimen: skin disinfection (chlorhexidine), local nasal antibiotic (mupirocin), and systemic antibiotic (clindamycin)., Methods: Patients attending our institution during the period 2006-2012 for recurrent furunculosis (≥ 4 episodes/y) were enrolled in the study. Clinical and bacteriological data were collected. Staphylococcus aureus colonization was also investigated in close contacts, and carriers were treated. Patients were treated with the CMC regimen: skin disinfection with chlorhexidine for 21 days, nasal mupirocin ointment for 5 days, and oral clindamycin 1800-2400 mg for 21 days., Results: Nineteen patients were included. Their mean age was 36 ± 14.5 y and the male to female sex ratio was 1.1. Screening swabs from all sites were S. aureus-positive in 63% (n = 12), including 4 methicillin-resistant S. aureus (MRSA). Before the CMC regimen, the median time to relapse was 31 days (mean 52 days). The mean number of recurrences was 5.5 ± 2.4/y. After the CMC regimen, among 16 patients who had a complete follow-up, 14 were healed beyond 9 months. Two recurrences occurred, 1 in an MRSA carrier and 1 in a patient with an insufficiently treated dermatosis. No serious side effect occurred that required the cessation of treatment., Conclusions: There are 2 major routes involved in recurrent furunculosis: risk factors and staphylococcal colonization of close contacts. Our procedure is safe and effective, with 87% remission beyond 9 months. It merits testing on larger numbers of participants.

Following the emergence of highly pathogenic avian influenza (AI), active surveillance of infections due to the H5 and H7 subtypes in poultry has increased and been made compulsory in Europe since 2002, by means of annual serological surveys using the haemagglutination inhibition (HI) test. Domestic anseriforms, particularly ducks and geese, are more frequently infected by H5 low pathogenic AI virus, often subclinically, and represent a threat for other terrestrial poultry. 1783 sera, mainly from ducks, have been used to evaluate and compare a commercial ELISA kit detecting H5 antibodies with the currently recommended HI test. Different approaches to calculating specificity and sensitivity have been used, including the original Bayesian method. Results were similar when data were analyzed at the individual and batch levels, and when using different methods of calculation. However, results showed that H5 ELISA had both a higher sensitivity and a lower specificity than the HI test. Given that sensitivity is the most important factor for a screening test, H5 ELISA could therefore be recommended for AI surveillance, followed in cases of positivity by molecular tests aimed at detecting the virus gene., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Combination antiretroviral therapy (cART) can cause potentially stigmatizing facial lipoatrophy. Encouraging preliminary results have been reported with 2.5% polyacrylamide hydrogel for facial reconstruction. The aim of this multicenter, open-label noncomparative pilot study was to evaluate the efficacy and safety of intradermal facial injections of polyacrylamide hydrogel in HIV-infected patients with severe facial lipoatrophy. The patients received between two and six injections every 4 weeks, according to the aesthetic results. Clinical efficacy was evaluated by means of facial ultrasonography and photography at baseline and months 6, 12, and 24. Adverse events, patient satisfaction, and quality of life were also assessed. One hundred and eleven patients were enrolled and received at least one injection. Mean cheek skin thickness was 9.7 mm [95% CI: 9.1 to 10.2] at baseline. It rose by an average of 4.4 mm [95% CI: 3.9 to 4.9; p<0.001] at month 12 and a further 0.87 mm [95% CI: 0.52 to 1.23; p<0.001] at month 24. The Overall Treatment Satisfaction scale showed an improvement in more than 88% of patients at all visits, based on the appreciations of the patients, their close relatives and physicians, and on independent assessment of facial photographs. Quality of life improved significantly over time, as shown by the lipodystrophy-specific ABCD scale. No severe adverse effects related to the polyacrylamide hydrogel were noted. Polyacrylamide hydrogel injections were well tolerated and significantly improved the aesthetic aspect and quality of life of HIV-infected patients with facial lipoatrophy.

The authors report here the results of study on Parkia biglobosa seeds used in Burkina Faso for arterial hypertension treatment. Investigations were done on acute toxicity and vascular properties of fermented and roasted seeds. Acute toxicity test using mice, revealed by the intraperitoneal route a lethal dose 50 (LD50) of 1800 mg/kg and 1600 mg/kg of body weight for aqueous extract from roasted and fermented seeds respectively. According to the scale of Hodge and Sterner and that of the World Health Organization, such drugs would be classified lightly toxic. Oral administration (up to 3000 mg/kg) did not induce any death of animal. For the vascular properties, the effects of these products were tested on the aorta isolated from rats. The cumulative administration of extract from roasted and fermented seeds (0.1-10 mg/mL) in an organ bath induced a concentration-dependent relaxation of the aorta pre contracted by phenylephrine, with or without functional endothelium. The extracts (10 mg/mL) inhibited for 100% the contraction induced by phenylephrine. The EC50 values in presence and absence of endothelium were respectively of 5.37 ± 0.12 and 4.19 ± 1.02 mg/mL for fermented seeds; for roasted seeds these values were respectively, 5.39 ± 1.12 and 5.93 ± 0.95 mg/mL. Nevertheless, low concentration of roasted seeds (1-4 mg/mL) induced endothelium-dependent relaxation and this effect was inhibited by indomethacin (10⁻⁵M), and not by L-NAME (310⁻⁴M). These experimental results revealed a vasorelaxant effect of P. biglobosa seeds. P. biglobosa seems to act directly on the smooth muscle and via endothelium involving the generation of vasodilatating prostaglandins. This vasodilator effect would be in favor of an anti hypertensive property of P. biglobosa seeds.

Objective: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans' cell histiocytosis that may present with pulmonary involvement. We undertook the current study to evaluate the characteristic features of pulmonary involvement in ECD, in the largest single-center series of patients reported to date., Methods: We performed a retrospective study of the characteristics of 34 consecutive patients with biopsy-proven ECD who were referred to the internal medicine department of Pitié-Salpêtrière Hospital between 1981 and November 2008., Results: Data were obtained from 23 men and 11 women. The median age at the time of diagnosis was 53.7 years (range 16-73 years), and the median followup was 3.5 years (1.4-5.3 years). Eight patients (24%) had pulmonary symptoms. High-resolution computed tomography (HRCT) scans of the chest revealed involvement of lung parenchyma in 18 patients (53%) and of the pleura in 14 patients (41%). Bronchoalveolar lavage fluid analysis revealed the presence of an opalescent aspirate in all the patients studied. Treatment with corticosteroids and/or interferon-α (IFNα) resulted in a marked improvement of the pulmonary lesions in only a single patient. Comparison of the survival between patients with and those without pulmonary involvement yielded no significant difference between the groups (P = 0.82)., Conclusion: Pulmonary involvement in ECD has been overlooked in previous studies. HRCT reveals typical lesions in most patients. There is no clear response of these lesions to corticosteroids and IFNα. The overall prognosis of the disease is poor, but pulmonary involvement does not appear to be a major prognostic factor in ECD., (Copyright © 2010 by the American College of Rheumatology.)

The presence of pleomorphic tumor giant cells in thyroid carcinomas of follicular cell origin is always worrisome for the pathologist as they first of all refer to anaplastic carcinoma, one of the most aggressive human malignancies. However, non-anaplastic pleomorphic giant cells are well described in other thyroid diseases, most often benign. In this paper, we describe four cases of papillary thyroid carcinoma displaying pleomorphic tumor giant cells with features that differ from those of anaplastic carcinoma. Pleomorphic giant cells were admixed with the underlying thyroid carcinoma and constituted from 5% to 25% of the tumor. Cytologically, they had an abundant eosinophilic cytoplasm with large and irregular nuclei. Compared to pleomorphic giant cells of anaplastic carcinoma, they reproduced the growth pattern of the underlying carcinoma, had a low mitotic index without necrosis or inflammation, and were reactive with thyroglobulin and thyroid-specific transcription factor-1 and strongly and diffusely positive for cytokeratin AE1/AE3. After 16-84 months of follow-up, patients are relapse-free and still alive. These cases show that pleomorphic tumor giant cells arising in papillary thyroid carcinomas do not always represent dedifferentiation and progression to anaplastic carcinoma. Distinction among these processes is critical as their treatment and prognosis are very different.

The HIV/AIDS pandemic disproportionately afflicts regions of the world that have minimal access to formal schooling and low literacy rates. Health educational interventions are difficult to evaluate efficiently in these settings because standard approaches such as written questionnaires cannot easily be employed. Here, we describe a novel method of rapidly assessing health interventions among large groups that does not require the ability to read or write. We tested this evaluation tool within the context of a community-based HIV/AIDS drama education program in a low-literate region of rural Haiti. The evaluation was simple, easy to use, and confirmed substantial improvements in knowledge after the intervention. The tool also provided information that helped alter the intervention to improve educational outcomes in subsequent productions of the drama. This evaluation method can be utilized for very little cost, and may be replicated in resource-poor, non-literate settings throughout the developing world.

Prevalence of avian influenza infection in free-range mule ducks (a cross between Muscovy [Cairina moschata domesticus] and Pekin ducks [Anas platyrhychos domesticus]) is a matter of concern and deserves particular attention. Thus, cloacal swabs were collected blindly from 30 targeted mule flocks at 4, 8, and 12 wk of age between October 2004 and January 2005. They were stored until selection. On the basis of a positive H5 antibody detection at 12 wk of age with the use of four H5 antigens, the samples from eight flocks were selectively analyzed. Positive samples were first screened with a matrix gene-based real-time reverse transcriptase-polymerase chain reaction assay before virus isolation. Eight avian influenza subtypes (H5N1, H5N2, H5N3, H6N2, H6N8, and H11N9) and three avian paramyxovirus type 1 viruses were isolated. All 11 are characterized as low pathogenicity (LP) and avirulent, respectively, by in vivo tests and, when relevant, nucleotide sequencing of the hemagglutinin (or fusion [F]) protein cleavage site. Regarding H5 isolates, all of their eight genes belong to the avian lineage and some particular genetic traits were determined. H5 genes were fully sequenced and phylogenetically analyzed; they all belong to the Eurasian lineage, lack additional glycosylation sites, and do not cluster, suggesting separate introductions from the wild reservoir. None were grouped with the Asian isolates. The N1 gene (H5N1 isolate) was very close genetically to an Italian LP-H7N1 gene. Antigenic relationships between these H5 isolates and others were assessed comparatively by crossed hemagglutination inhibition tests. All these data are very useful to control the evolution of H5 viruses at the genetic and antigenic level to better understand the source of new outbreaks (new introductions from wild birds or the result of spread among poultry) and to assess the immunity afforded by available vaccines. These data are useful also to update antigens for avian influenza survey and to choose the most suitable vaccine in the case of preventive vaccination of ducks.

Aqueous extracts of Mitragyna inermis (AEMI) used traditionally as antihypertensive agents produced a concentration-dependent (0.1-3 mg/ml) ex vivo increase in cardiac contractile response and coronary flow but did not modify heart rate in the rat. Interestingly, AEMI produced relaxation in isolated porcine coronary artery at concentration up to 3 mg/ml that was exclusively dependent on the presence of endothelium. This relaxation involved partial depolarization (KCl 20, 40 mM) and NO synthase inhibitor-sensitive mechanisms but was not sensitive to the blockade of cyclo-oxygenase pathway. In contrast, the relaxant effect of AEMI was not dependent on the presence of endothelium in rat tail artery. Taken together, the present study demonstrates hypotensive, cardiotropic and vasodilatory properties of AEMI that contribute to better understanding of its beneficial effect against cardiovascular diseases.

Background: The Trauma Evaluation and Management (TEAM) module was devised by the American College of Surgeons for teaching senior medical students trauma management principles. This article reports on the teaching effectiveness of this module., Method: Cognitive skills (by 20 item multiple-choice question examination on trauma topics) and clinical trauma management skills performance, using the Objective Structured Clinical Examination, were compared between two groups of 16 randomly selected final year medical students who had completed the standard curriculum including trauma topics. One group had the TEAM (TEAM group) and the other did not (no-TEAM group). Objective Structured Clinical Examination score (percentage), Priority score (range, 1-7), Organized Approach score (range, 1-5), and Global Pass status were assigned at each station. The students also completed a five-part questionnaire., Results: Results of the questionnaire showed that on a scale of 1 to 5, with 5 being excellent, 96.8% assigned a score of 4 or greater, indicating the objectives were met, 83.8% that trauma knowledge was improved, 51.6% that clinical skills were improved, 90.3% that the module should be mandatory, and 83.9% overall satisfaction with the program., Conclusion: The TEAM module is very effective in teaching trauma management principles to senior medical students, by whom the program was very well received. Consideration should be given to adopting this program more widely in our medical undergraduate curriculum.

Background: We previously (1997) demonstrated superior clinical but similar cognitive performance after the new interactive compared to the old ATLS course. The present study is aimed at determining whether this difference was short term or maintained over time (2 years)., Materials and Methods: Two groups of 13 physicians out of the original 32 physicians were available for the study which compared performance in a 40-item MCQ examination on trauma topics and clinical performance in 4 trauma OSCE stations consisting of simulated trauma patients. Paired and unpaired t tests were used for within- and between-group comparisons, respectively, with P < 0.05 being considered statistically significant. Overall OSCE scores (maximum standard 20), adherence to priority scores (Priority, scale 1 to 7), and overall approach (Approach, scale 1 to 5) scores were analyzed., Results: Values are means +/- SD; (+)-P < 0.05 compared to 1999; *P < 0.05 compared to old group [table in text]., Conclusions: Although knowledge base decreases similarly with time after both courses, the new interactive course participants maintained a consistently higher clinical skill performance level at 2 years., (Copyright 2001 Academic Press.)

Status epilepticus (SE) is a condition requiring emergency care, which is often poorly managed in developing countries due to the lack of personnel, drugs, and insufficient technical and medical means. This study aims at determining the epidemiologic and etiologic characteristics and the difficulty in treating SE under the existing medical practice conditions in a developing country such as Senegal. A retrospective study was therefore carried out based on SE medical files at the University Hospital of Dakar over the period January 1988 to December 1998, and included several hospital departments, i.e., paediatrics, infectious diseases and neurology. Over an 11-year period 697 cases were recorded; of these, 48.2% of patients were under 5 years of age. The seizures were generalized in 58.2% of cases, partial in 21.2%, partial secondarily generalized, or with an association of both clinical presentations in 20.6% of cases. The etiology was as follows: mainly infectious (67%), followed by resistant and/or unbalanced epilepsy (9.9%), epilepsy of vascular origin (8%), and various other causes. The overall mortality rate was 24.8%. A long period between the onset of clinical symptoms and hospital treatment was noted, with an average time lapse of 16.6 h before treatment. The drugs utilized were diazepam and phenobarbitol, administered by injection. The overall outcome could be improved by better management, i.e., better prevention and an efficient treatment of infectious diseases, a reduction in the time before treatment, and improved means of intensive care.

Background: The 1997 edition of the Advanced Trauma Life Support (ATLS) course emphasized interactivity as its major change. The impact of this change is assessed in this study., Methods: We compared two matched groups of 16 interns completing either the old (group I) or new (group II) ATLS course. Cognitive skills (40 standard ATLS questions plus 10 additional questions on airway and shock) and clinical trauma management skills (four trauma objective structured clinical examinations [OSCEs] on simulated trauma patients) were tested. OSCE station scores (standardized to a maximum of 20), priority scores (graded 1-7), organized approach global passing grades (graded 1-5), and initial assessment test station scores (graded 1-5) were compared., Results: Using ATLS criteria, three interns failed in each group. Post-ATLS examination question scores were similar (84.5+/-6.9 for group I, 85.9+/-7.1 for group II); scores for the airway and shock questions were higher but not different between the two groups. The four OSCE station mean scores varied between 13.9+/-2.0 and 15.4+/-2.1 for group I and were higher (p < 0.05) for group II (17.9+/-1.6 to 19.1+/-1.0). Priority scores were similar (group I, 6.3+/-1.1; group II, 6.4+/-1.2), but approach scores (3.9+/-0.1 for group I and 4.9+/-0.8 for group II) were lower in group I, as were the initial assessment test scores (2.9+/-0.2 for group I and 4.9+/-0.8 for group II). There were 8 honors grades in group I and 40 (p < 0.05) in group II. Interactive teaching, adult education principles, opportunities for discussion, provision of feedback, and stimulation of self-learning were rated more highly in the new course., Conclusion: Using standard ATLS pass criteria, performance after the new and old ATLS courses was similar. Superior performances were measured using OSCE methodology for clinical trauma management skills after the new compared with the old ATLS course in this population of interns.

We tested the effectiveness of a basic prehospital trauma life support (PHTLS) program by assessing cognitive performance and trauma management skills among prehospital trauma personnel. Fourteen subjects who completed a standard PHTLS course (group I) were compared to a matched group not completing a PHTLS program (group II). Cognitive performance was assessed on 50-item multiple choice examinations, and trauma skills management was assessed with four simulated trauma patients. Pre-PHTLS multiple choice questionnaire scores were similar (45.8 +/- 9.4% vs. 48.8 +/- 8.9% for groups I and II, respectively), but the post-PHTLS scores were higher in group I (80.4 +/- 5.9%) than in group II (52.6 +/- 4.9%). Pre-PHTLS simulated trauma patient performance scores (standardized to a maximum total of 20 for each station) were similar at all four stations for both groups, ranging from 7.9 to 10.4. The post-PHTLS scores were statistically significantly higher at all four stations for group I (range 16.0-19.0) compared to those for group II (range 8.0-11.1). The overall mean pre-PHTLS score for all four stations was 8.3 +/- 2.1 for group I and 8.8 +/- 2.0 (NS) for group II; the group I post-PHTLS mean score for the four stations was 17.1 +/- 2.7 (p < 0.05) compared to 9.1 +/- 2.3 for group II. Pre-PHTLS Adherence to Priority scores on a scale of 1 to 7 were similar (1.1 +/- 0.9 for group I and 1.2 +/- 1.0 for group II). Post-PHTLS group I Priority scores increased to 5.9 +/- 1.1. Group II (1.1 +/- 1.0) did not improve their post-PHTLS scores. The pre-PHTLS Organized Approach scores in the simulated trauma patients on a scale of 1 to 5 were 2.1 +/- 1.0 for group I and 1.9 +/- 1.2 for group II (NS) compared to 4.2 +/- 0.9 (p < 0.05) in group I and 2.0 +/- 0.8 in group II after PHTLS. This study demonstrates improved cognitive and trauma management skills performance among prehospital paramedical personnel who complete the basic PHTLS program.

Vinflunine, or 20',20'-difluoro-3',4'-dihydrovinorelbine, is a novel Vinca alkaloid obtained by hemisynthesis using superacidic chemistry. The most impressive structural modification of this vinorelbine derivative was the selective introduction of two fluorine atoms at the 20' position, a part of the molecule previously inaccessible by classic chemistry. The antitumor activity of vinflunine was evaluated against a range of transplantable murine and human tumors. Vinflunine exhibited marked activity against murine P388 leukemia grafted i.v. when given i.p. in single or multiple doses according to various schedules or in single i.v. or p.o. doses. Increases in life span achieved with vinflunine, as assessed by T/C ratios, ranged from 200% to 457% and proved markedly superior to those of 129-186% obtained with the other Vinca alkaloids tested. Against s.c.-implanted B16 melanoma, multiple i.p. administration of vinflunine proved active in terms of both survival prolongation and tumor growth inhibition, with optimal T/C values and relative areas under the tumor growth curves (rAUC) being 24% and 36%, respectively. The extent of this activity was superior to that noted for vinorelbine under the same experimental conditions. Growth inhibition of human tumor xenografts LX-1 (lung) and MX-1 (breast) was also observed following four weekly i.p. injections of vinflunine as reflected by optimal T/C values of 23% and 26%, respectively, and significant differences in the rAUCs noted for treated versus control animals. It was also noticeable that vinflunine induced considerably more prolonged inhibitory effects on tumor growth than did vinorelbine. These results demonstrate that vinflunine is well tolerated and is definitively active against a range of experimental animal tumor models. Vinflunine activity has been documented in terms of both survival prolongation and tumor growth inhibition, with definite superiority over vinorelbine being shown in each tumor model evaluated.

Although the Advanced Trauma Life Support (ATLS) course is now taught internationally, its teaching effectiveness still requires confirmation. The Objective Structured Clinical Examination (OSCE) reliably assesses clinical performance by utilizing standardized patients. An OSCE of eight 15 minute trauma patient stations and two 40 item MCQ tests were used to test the teaching effectiveness of the ATLS program in 32 practicing physicians who applied for an ATLS program in Trinidad and Tobago. The physicians were randomly assigned to an ATLS group (n = 16) that completed the ATLS course and a non-ATLS group (n = 16). Before and after the ATLS course, all physicians completed MCQ tests and trauma OSCE. Mean (+/- SD) OSCE scores (standardized to 20) ranged from 9.8 +/- 1.7 to 10.0 +/- 1.7 and 9.5 +/- 1.8 to 10.8 +/- 1.3 in the ATLS and non-ATLS groups, respectively, prior to the ATLS course (NS). Post-ATLS OSCE scores ranged from 15.9 +/- 1.7 to 17.6 +/- 1.7 in the ATLS group (p < 0.05 compared to pre-ATLS) and 9.5 +/- 1.4 to 10.1 +/- 1.3 in the non-ATLS group, which did not improve their OSCE scores. Adherence to priorities was graded 1 to 7 with the pre-ATLS grades of 1.7 +/- 0.6 (ATLS) and 1.8 +/- 0.7 (non-ATLS) and post-ATLS grades of 6.4 +/- 1.1 (ATLS) and 2.1 +/- 0.6 (non-ATLS). Organized approach to trauma was graded 1 to 5 with pre-ATLS grades of 1.6 +/- 0.5 (ATLS) and 1.7 +/- 0.6 (non-ATLS) and post-ATLS grades of 4.5 +/- 0.6 (ATLS) and 1.9 +/- 0.6 (non-ATLS). Pre-ATLS MCQ scores (%) were similar: 53.1 +/- 8.4 (ATLS) and 57.3 +/- 5.4 (non-ATLS), but post-ATLS scores were greater in the ATLS group: 85.8 +/- 7.1 (ATLS) and 64.2 +/- 3.6 (non-ATLS). Our data support the teaching effectiveness of the ATLS program among practicing physicians as measured by improvement in OSCE scores, adherence to trauma priorities, maintenance of an organized approach to trauma care, and cognitive performance in MCQ examinations.

Objective: To test the attrition of cognitive and trauma management skills among practising physicians after the Advanced Trauma Life Support (ATLS) course., Design, Materials, and Methods: Sixty practising physicians who completed the ATLS course had comparative assessment of cognitive skills (with multiple choice questions, MCQ) pre-ATLS, immediately post-ATLS, at 6 months (group A), 2 years (group B), 4 years (group C), and 6 years (group D) after the course. Trauma management skills were also compared using eight Objective Structured Clinical Examination (OSCE) trauma stations completed by the four groups of physicians., Measurements and Main Results: Pre-ATLS MCQ scores (54.2 +/- 4.2 to 59.8 +/- 5.3%) and immediately post-ATLS MCQ scores (85.9 +/- 5.1 to 87.7 +/- 5.3%) were similar in all four groups. Follow-up MCQ scores were 77.8 +/- 3.6% at 6 months 70.6. +/- 1.9% at 2 years, 69.4 +/- 1.7% at 4 years, and 68.9 +/- 2.0% at 6 years. OSCE scores out of a maximum of 20 were 16.8 +/- 0.3 at 6 months, 13.9 +/- 0.1 at 2 years, 12.0 +/- 0.1 at 4 years, and 11.9 +/- 0.1 at 6 years. Adherence-to-priorities scores (maximum, 7) were 6.6 +/- 0.2 at 6 months, 6.8 +/- 0.1 at 2 years, 6.6 +/- 0.1 at 4 years, and 6.6 +/- 0.1 at 6 years. Organized-approach scores (maximum, 5) were 4.8 +/- 0.1 at 6 months, 4.6 +/- 0.2 at 2 years, 4.7 +/- 0.2 at 4 years, and 4.6 +/- 0.2 at 6 years. Using the MCQ 80% pass mark criterion, at least 50% of physicians fail by 6 months and all fail this cognitive test thereafter., Conclusions: Whereas cognitive and trauma management skills decline after the ATLS, these skills are maintained at similar levels between 4 and 6 years after ATLS. A 50% failure rate occurs within 6 months and maximum attrition of cognitive skills occurs within 2 years of ATLS completion. Major principles of adherence to priorities and maintenance of an organized approach to trauma care are preserved for at least 6 years after ATLS.

In spite of a lack of compounds acting selectively at the 5-hydroxytryptamine (5-HT)1B and 5-HT1D receptor subtypes, by cross-relating the available data, this review attempts to tentatively assign behavioural and other in vivo correlates of these receptor subtypes. In addition, a summary of data from microdialysis studies is included to develop an integrated view. Finally, a suggestion is made as to the possible pathophysiological consequences of 5-HT1D receptor dysfunction in man.