Search

The disk diffusion test is very popular but for anaerobes the main pitfalls arise from the significant variation of diameters for an individual MIC and the weak correlation observed between the MIC's values and diameters zone that generates many major and very major errors. Aims of the study without any change in the methodology and revisiting only new diameter breakpoints, we try to improve the previous French recommendations and therefore decrease number of errors by introducing recent EUCAST concepts such as ECOFF and ATU Zone. Method MIC determination by agar dilution was done on 100 anaerobes against 6 antibiotics. Clinical categorization was based on EUCAST Breakpoints. Disk-diffusion method was realized on the same Brucella blood agar incubated in an anaerobic chamber. 550 categorizations by both methods could be done as amoxicillin was not tested on the 50 B. fragilis group. As anaerobic infections are severe and treated by antibiotics at higher dosage, we focus on resistance breakpoint to avoid mainly very major errors (VME). Distribution of inhibition zones for each MIC allow us to fix the zone diameter breakpoints. These results were matched to a large data on distribution of zone diameters for each antibiotic collected from two French hospitals from 1990 to 2005. As example for metronidazole and the B. fragilis group, we calculated the cut-off diameter (15 mm) from a wild type population, at a time when there was no resistance to this antibiotic and observed that it was identical to the diameter breakpoint for susceptibility. Results For an individual value of MIC, the distribution of diameters is wider for anaerobes especially for clindamycin and metronidazole. Using a 15 mm breakpoint for these two antibiotics limits dramatically the number of very major errors but slowly increases the number of major errors that could be overcome by MIC determination if inhibition zone is less than 15 mm. ATU zones (Area of technical uncertainty) were introduced for amoxicillin-clavulanate (17–20 mm), piperacillin-tazobactam (17–20 mm), imipenem (18–23 mm). Categorization inside the ATU requires MIC determination. Finally, out of 550 determinations, VME were observed in 1.45% of cases, an acceptable rate. Conclusion in combination with introduction of ATU zones disk diffusion method allows to detect resistant strains with little MIC determinations and very major errors.

In 2016, the Patient-Centered Outcomes Research Institute funded the National Patient Centered Clinical Research Network (PCORnet) Bariatric Study (PBS). Understanding the experience of postoperative patients was a key component of this study. Nine focus groups were conducted in Southern California, Louisiana, Pennsylvania, and Ohio and in a national advocacy conference for patients with obesity. Participants were identified and recruited in both clinical and community settings. Focus group transcripts were analyzed using an iterative inductive-deductive approach to identify global overarching themes. There were 76 focus group participants. Participants were mostly women (81.4%), had primarily undergone gastric sleeve (47.0%), were non-Hispanic white (51.4%), had some college education (44.3%), and made $100,000 annual income or less (65.7%). Qualitative findings included negative reactions patients received from friends, family, and co-workers once they disclosed that they had bariatric surgery to lose weight; and barriers to follow-up care included insurance coverage, emotional and situational challenges, and physical pain limiting mobility. These findings confirm the other qualitative findings in this area. The approach to bariatric surgery should be expanded to provide long-term comprehensive care that includes in-depth postoperative lifetime monitoring of emotional and physical health.

Objectives The aim was to assess the incidence of sink contamination by multidrug-resistant (MDR) Pseudomonas aeruginosa and Enterobacteriaceae, risk factors for sink contamination and splashing, and their association with clinical infections in the intensive care setting. Methods A prospective French multicentre study (1 January to 30 May 2020) including in each intensive care unit (ICU) a point-prevalence study of sink contamination, a questionnaire of risk factors for sink contamination (sink use, disinfection procedure) and splashing (visible plashes, distance and barrier between sink and bed), and a 3-month prospective infection survey. Results Seventy-three ICUs participated in the study. In total, 50.9% (606/1191) of the sinks were contaminated by MDR bacteria: 41.0% (110/268) of the sinks used only for handwashing, 55.3% (510/923) of those used for waste disposal, 23.0% (62/269) of sinks daily bleached, 59.1% (126/213) of those daily exposed to quaternary ammonium compounds (QACs) and 62.0% (285/460) of those untreated; 459 sinks (38.5%) showed visible splashes and 30.5% (363/1191) were close to the bed ( Discussion Our data showed frequent and multifactorial infectious risks associated with contaminated sinks in ICUs.

Objective: Due to the natural aging and the loosened CI-implantation criteria more formerly operated Meniere's patients will be supplied with a cochlear implant. However, it raises the question whether an implantation in a previously treated ear is promising. Material and Methods: Based on 2 cases in which we have carried out a CI-implantation, one of them 10 years after transmastoidal labyrinthectomy, and based on the current literature we draw attention to problems and prospects of success. Discussion: Histological studies show only a small ossification of the cochlea after labyrinthectomy. Implanted Meniere's patients have a better speech intelligibility than other CI users. Attacks of rotatory vertigo with tinnitus and fluctuations of hearing after cochlear implantation in Meniere's patients are rare or they are too little described. Conclusion: There is a trend to perform a simultaneous labyrinthectomy and cochlea implantation in Meniere's patients with desabling vertigo which have not responded to drug treatment. A formerly performed transmastoidal labyrinthectomy is not a contraindication for a cochlear implantation.

International audience; ObjectivesWe previously described extended-spectrum oxacillinase OXA-145 from Pseudomonas aeruginosa, which differs from narrow-spectrum OXA-35 by loss of Leu-155. The deletion results in loss of benzylpenicillin hydrolysis and acquisition of activity against ceftazidime. We report the crystal structure of OXA-145 and provide the basis of its switch in substrate specificity.MethodsOXA-145 variants were generated by site-directed mutagenesis and purified to homogeneity. The crystal structure of OXA-145 was determined and molecular dynamics simulations were performed. Kinetic parameters were investigated in the absence and in the presence of sodium hydrogen carbonate (NaHCO3) for representative substrates.ResultsThe structure of OXA-145 was obtained at a resolution of 2.3 Å and its superposition with that of OXA-10 showed that Trp-154 was shifted by 1.8 Å away from the catalytic Lys-70, which was not N-carboxylated. Addition of NaHCO3 significantly increased the catalytic efficiency against penicillins, but not against ceftazidime. The active-site cavity of OXA-145 was larger than that of OXA-10, which may favour the accommodation of large molecules such as ceftazidime. Molecular dynamics simulations of OXA-145 in complex with ceftazidime revealed two highly coordinated water molecules on the α- or β-face of the acyl ester bond, between Ser-67 and ceftazidime, which could be involved in the catalytic process.ConclusionsDeletion of Leu-155 resulted in inefficient positioning of Trp-154, leading to a non-carboxylated Lys-70 and thus to loss of hydrolysis of the penicillins. Ceftazidime hydrolysis could be attributed to enlargement of the active site and to a catalytic mechanism independent of the carboxylated Lys-70.

Steel-based composites reinforced with titanium diborides (TiB 2 ) and produced by eutectic solidification display a significant increase in specific stiffness ( E / ρ ) in comparison with usual steels. A significant lightening can be achieved in parts designed for stiffness with a high Young’s modulus and a low density. They can be produced through the use of industrial continuous casting devices and can be hot rolled without any damage. This production route guarantees a good cohesion of the steel/reinforcement interface and the control of the main parameters that determine the final properties of the product (size, shape, clustering of reinforcements). In order to get a better understanding of the composite properties, its microstructural features after hot rolling are investigated through transmission electron microscopy at microscopic and atomic levels. TiB 2 reinforcements are homogeneously distributed in the ferritic iron matrix. Interfaces between Fe and TiB 2 particles are mainly parallel to dense planes of the diboride, with a preferential growth of prismatic planes { 1 0 1 ¯ 0 } . Interfacial misfit dislocations occur at interfaces parallel to the prismatic planes. The TiB 2 basal plane is covered by a TiC layer three atomic planes in width. The hot rolling operation induces a significant plastic deformation in the TiB 2 particles, with the activation of basal and prism plane slip systems. All these characteristics may account for the good behaviour of the composite in terms of hot rolling capability.

Background Chromosomal class A β-lactamases have been characterized in Raoultella ornithinolytica and Raoultella planticola. The purpose of this study was to characterize that of Raoultella terrigena. Materials and methods The blaTER-1 gene of R. terrigena strain ATCC33257T was cloned (pACter-1) and sequenced. It was then used to detect the bla gene of strains BM 85 01 095 and SB2796. The hypermutable Escherichia coli strain AB1157 mutS::Tn10 was transformed with pACter-1 and mutants growing on plates containing > 2 mg/L ceftazidime were studied. Notably, the impact of mutations only observed in the promoter region on β-lactam resistance was assessed by site-directed mutagenesis experiments. Results R. terrigena strains ATCC33257T and BM 85 01 095 had the same bla gene and deduced protein (TER-1) whereas there were 3 substitutions in those of strain SB2796 (TER-2). Class A β-lactamases TER showed 78%, 69.9% and 38.7% identity with PLA or ORN, TEM-1 and KOXY, respectively. Compared with TEM-1, TER-1 and TER-2 showed 2 particular substitutions, Leu75Pro and Glu240Asn demonstrated to be involved in the inherent β-lactam resistance profile of R. terrigena. TER-1 (pI of 7.6) had a high activity against penicillin G and a significantly low one against amoxicillin. Substitution G/T observed in the -35 region of the blaTER gene harbored by strains growing in the presence of ≥ 2 mg/L ceftazidime was shown to be responsible for this growth. Conclusion TER is a new class A β-lactamase belonging to functional group 2b.

Cephalosporinases, which are naturally present in some enterobacterial species, can be mobilized by transposons, migrate to plasmids, and spread into other species such as Escherichia coli. The aim of this study was to characterize genes responsible for the production of extended-spectrum β-lactamases (ESBL) in E. coli isolates from urinary origin isolated in two hospitals in Senegal. Thus, a fortuitous discovery of plasmidic cephalosporinase in two isolates was noted. One of the isolates produced dha-1 associated with ESBL CTX-M-14, the other produced cmy-2, ESBL CTXM-15, tem-1 penicillinase, and oxa-1. This confirms the circulation of multidrug-resistant bacteria producing plasmidic cephalosporinase in Senegal. However, a large study is needed to better understand the prevalence and the nature of the genes involved.

Objectives To decrease the incidence of early-onset group B streptococcal (GBS) disease, a culture-based screening of all pregnant women at 35–37 weeks is recommended. This gold standard test requires 24–72 hours culture. This delay precludes its use for intrapartum screening. This study assesses a new immunoassay, the DIMA test, for identifying GBS-positive patients in the labor ward. Materials and methods This was a prospective observational study of 195 pregnant women presenting with full-term labor at a single site in France between June and August 2012. We assessed the diagnostic accuracy of intrapartum DIMA testing as compared to intrapartum GBS culture and prenatal screening at 35–38 weeks. Results The DIMA test sensitivity and specificity were 57.1% and 83.2%, respectively, as compared to 42.9% and 97% for prenatal culture screening. Conclusion The DIMA test assay is a rapid and inexpensive test for the detection of maternal GBS colonization in the labor ward. Its sensitivity is higher than antepartum culture but its specificity is lower. Its performance was inferior to that reported for rapid polymerase chain reaction assays.

Neuroendokrine Neoplasien der Lunge leiten sich von diffus im Korper verteilten enterochromaffinen Zellen her. Die Inzidenz der neuroendokrinen Neoplasien der Lunge ist in den letzten Jahrzehnten aufgrund der zur Verfugung stehenden Diagnostik deutlich angestiegen, sie machen etwa 1 – 2 % aller Lungentumoren und ca. 20 – 30 % aller neuroendokrinen Neoplasien aus. Die aktuelle WHO-Klassifikation ist aus dem Jahre 2004 und unterteilt typische Karzinoide (TC), atypische Karzinoide (AC), groszellige Lungenkarzinome (LCNEC) und kleinzellige Lungenkarzinome (SCLC). Die wichtigsten neuroendokrinen Biomarker sind Chromogranin A, CD56 und Synaptophysin. TC haben eine geringe Mitoserate von Die steigende Zahl der therapeutischen Moglichkeiten und diagnostische Verfahren erfordert ein multidisziplinares Vorgehen und eine Entscheidungsfindung in multidisziplinaren Tumorkonferenzen, um eine „masgeschneiderte“ Therapie zu gewahrleisten, weshalb Patienten mit einer neuroendokrinen Neoplasie der Lunge in spezialisierten Zentren behandelt werden sollten.

Since the last decade, lightening of automotive structure was mainly achieved by gauge reduction using ultrahigh strength steels such as dual phase and transformation induced plasticity grades. However, gauge reduction can significantly reduce the stiffness. Limits are today reached for some applications such as chassis/suspension part. Development of steel with improved specific stiffness becomes more and more relevant to go further in weight reduction. Development of steel matrix composites (SMCs) with ceramic reinforcements is a promising solution. With an appropriate selection of the ceramic, eutectic solidification can be achieved. This natural production route guarantees a good cohesion of the steel/reinforcement interface and the control of the main parameters, which provide final properties of the product (size, shape, clustering of reinforcement). Significant fraction of ceramic can be obtained (10–25 vol.-%). Eutectic SMC can be produced with conventional industrial process such as conti...

Resume Introduction Le syndrome de Churg-Strauss est une vascularite systemique rare. Cette maladie est responsable d’un infiltrat eosinophile des tissus dont les manifestations les plus frequentes sont l’asthme cortico-dependant, une mono- ou multinevrite, une polypose des sinus de la face, des atteintes digestive et renale. L’atteinte des glandes salivaires est exceptionnelle. Observation Nous decrivons les caracteristiques d’une atteinte salivaire parotidienne bilaterale chez une patiente porteuse de ce syndrome. Le bilan morphologique detaille des glandes salivaires a mis en evidence un epaississement inhabituel des parois des canaux salivaires. Discussion Generalement au second plan du tableau clinique, et source d’errements diagnostiques, l’atteinte salivaire du syndrome de Churg et Strauss peut etre delicate a demontrer histologiquement. Il est recommande de realiser un prelevement tissulaire dans la glande responsable de la symptomatologie, en dehors de tout traitement corticoide.

Bei der hereditaren hamorrhagischen Teleangiektasie (HHT, Morbus Osler-Weber-Rendu) kann es zur Ausbildung von pulmonalen arteriovenosen Malformationen (pAVM) kommen. Zur Vermeidung von Komplikationen und zum Verschluss relevanter AV-Shunts sollte eine Embolisation der Malformationen vorgenommen werden. Im vorliegenden Fallbeispiel kam es zum Abhusten von Embolisationsspiralen 15 Jahre nach Intervention. Bei Hamoptysen nach Interventionen mit Embolisationsspiralen sollte auch Jahre nach deren Implantation neben dem Verdacht auf neue AV-Malformationen an durchwanderte Spiralen gedacht und eine entsprechende Diagnostik durch Einsatz von Thorax-CT mit Kontrastmittel und Bronchoskopie durchgefuhrt werden.

Introduction: CT alone cannot provide sufficient information referring to response after neoadjuvant therapy in a timely manner. To evaluate the role of 18F-FDG-PET after neoadjuvant chemoradiation as a valid, non-invasive predictor for early therapy response and its effect on survival as compared to histopathologic tumor response, data of 32 of 210 randomized patients with NSCLC stage IIIA/IIIB, who were treated in a prospective randomized controlled multicenter trial (LUCAS- MD), were re-evaluated. Material and Methods: For 32 patients with NSCLC stage IIIA (44%) IIIB (56%) neoadjuvant treatment consisted of two to three cycles of chemotherapy (225 mg/m2 paclitaxel and carboplatin AUC 6 d1q22) and concomitant chemoradiation (50 mg/m2 paclitaxel and carboplatin AUC 2 d1, d8, d15; 1.5 Gy b.i.d. up to 45 Gy). Documentation of involved lymph node stations as detected by 18F-FDG-PET/CT and lymph node sampling during surgery according to the IASLC lymph node mapping (2009). Evaluation of histological regression grade (RG) according to Junker et al. (2001) and correlation with 18F-FDG-PET/CT for primary tumor and each lymph node station. Calculation of disease free survival using Kaplan-Meier estimates and log rank tests. Results: Actuarial tumor specific survival for the 32 patients with concomitant chemoradiation plus chemotherapy: complete vs. incomplete metabolic remission prior to surgery after 60 months: 40% vs. 24% (p = 0.018). RG III/IIb (no/less than 10% of vital tumor cells) vs. RG IIa/I (more than 10% vital tumor cells) after 60 months: 46% vs. 15% (p = 0.006). 18/32 (56%) patients had RG III/IIb, 8/32 (25%) patients had regression grade III. 1/8 pts. with RG III were in the 18F-FDG- PET/CT false positive, 10 pts. with RG IIb (i.e. all pts. with RG IIb) were in the 18F-FDG-PET/CT false negative. One patient with RG IIa was in the 18F-FDG-PET/CT false negative. Hence, the cut-off level in detecting vital tumor cells by 18F-FDG-PET/CT after neoadjuvant chemoradiation for NSCLC is about 10%. Conclusion: Histological regression grading correlates well with metabolic remission as detected by 18F-FDG-PET. Thus, 18F-FDG-PET precedes CT in measuring the tumor response and may predict long-term therapeutic outcome in patients with stage III NSCLC. Invasive staging procedures may be avoided and patients who will not profit from resection due to insufficient downstaging after neoadjuvant treatment will be easily detected by using 18F-FDG-PET as standard imaging in workup and evaluation of treatment response.

International audience; Plasmid-mediated quinolone resistance mechanisms have become increasingly prevalent among Enterobacteriaceae strains since the 1990s. Among these mechanisms, AAC(6')-Ib-cr is the most difficult to detect. Different detection methods have been developed, but they require expensive procedures such as Sanger sequencing, pyrosequencing, polymerase chain reaction (PCR) restriction, or the time-consuming phenotypic method of Wachino. In this study, we describe a simple matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) method which can be easily implemented in clinical laboratories that use the MALDI-TOF technique for bacterial identification. We tested 113 strains of Enterobacteriaceae, of which 64 harbored the aac(6')-Ib-cr gene. We compared two MALDI-TOF strategies, which differed by their norfloxacin concentration (0.03 vs. 0.5 g/L), and the method of Wachino with the PCR and sequencing strategy used as the reference. The MALDI-TOF strategy, performed with 0.03 g/L norfloxacin, and the method of Wachino yielded the same high performances (Se = 98 %, Sp = 100 %), but the turnaround time of the MALDI-TOF strategy was faster (< 5 h), simpler, and inexpensive (< 1 Euro). Our study shows that the MALDI-TOF strategy has the potential to become a major method for the detection of many different enzymatic resistance mechanisms.

Fragment-based design was used to guide derivatization of a lead series of β-lactamase inhibitors that had heretofore resisted optimization for in vivo activity. X-ray structures of fragments overlaid with the lead suggested new, unanticipated functionality and points of attachment. Synthesis of three derivatives improved affinity over 20-fold and improved efficacy in cell culture. Crystal structures were consistent with the fragment-based design, enabling further optimization to a K i of 50 pM, a 500-fold improvement that required the synthesis of only six derivatives. One of these, compound 5 , was tested in mice. Whereas cefotaxime alone failed to cure mice infected with β-lactamase-expressing Escherichia coli , 65% were cleared of infection when treated with a cefotaxime: 5 combination. Fragment complexes offer a path around design hurdles, even for advanced molecules; the series described here may provide leads to overcome β-lactamase-based resistance, a key clinical challenge.

Hintergrund: Neuroendokrine Tumore der Lunge weisen eine deutlich ansteigende Inzidenz auf. Uber Diagnose und Therapie dieser Tumoren existieren jedoch nur wenig gesicherte Informationen. Demgegenuber liegen deutlich mehr Daten fur die neuroendokrinen Tumore des gastroenteropankreatischen Systems vor. Methode: Dialog mit Fachexperten fur neuroendokrine Tumore (NET) des gastroenteropankreatischen Systems und der Lunge am 25. und 26. Februar 2011 in Weimar, um Gemeinsamkeiten und Unterschiede zwischen den neuroendokrinen Tumoren der Lunge und des gastroenteropankreatischen Systems herauszustellen. Ergebnisse: Die neuroendokrinen Tumoren der Lunge weisen viele Gemeinsamkeiten, aber auch einige Unterschiede mit den gastroenteropankreatischen NETgastroenteropankreatischen Tumoren auf. Gemeinsamkeiten bestehen vor allem in der Pathologie, der Diagnosestellung und der Therapie. Unterschiede bestehen in den Empfehlungen zur systemischen Therapie und der deutlich geringeren Inzidenz paraneoplastischer Syndrome. Das Somatostatinrezeptor-PET/CT mit Gallium-68 konjugierten Somatostatinanaloga und die Peptid-Rezeptor vermittelte Radiorezeptortherapie sind innovative Verfahren fur die neuroendokrinen Tumore der Lunge. An erster Stelle der Therapie steht jedoch die komplette kurative Resektion. Erste Ergebnisse von Studien mit molekularen Wirkstoffen wie Everolimus (Afinitor®) zeigen eine Wirksamkeit an. Schlussfolgerungen: Es existieren deutliche Schnittmengen in der Diagnose und Therapie der neuroendokrinen Tumore der Lunge und des gastroenteropankreatischen Systems. Weitere Studien sind geplant und notwendig, um die Datenlage zu verbessern. Ein Register zur Erfassung der neuroendokrinen Tumore der Lunge ware sinnvoll.

Resume Introduction L’os spongieux est le materiau de comblement de choix dans la reconstruction de la fente alveolaire (alveoloplastie secondaire). Le prelevement iliaque est le plus classique mais sa morbidite est importante. Parmi les autres sites proposes, le prelevement tibial semble plus sur avec une morbidite moindre. Nous avons evalue les consequences du prelevement tibial medioproximal sur 55 enfants operes d’une alveoloplastie secondaire. Patients et methode Un questionnaire individuel a evalue retrospectivement l’intensite et la duree de la douleur postoperatoire, l’impotence fonctionnelle, d’eventuelles complications tardives et la longueur de la cicatrice. Des radiographies tibiales postoperatoires de face et de profil ont permis de mesurer le diametre de la corticotomie, sa distance avec l’espace articulaire et avec le cartilage de croissance, et de rechercher des complications locales. Resultats L’âge moyen etait de neuf ans. Aucune complication n’a ete relevee. Soixante-neuf pour cent des patients se sont plaints de douleur postoperatoire cotee 4/10 pendant une duree de 17 jours en moyenne. Soixante-cinq pour cent ont eu une gene a la marche pendant 12 jours en moyenne. La longueur de la cicatrice etait de 10 mm en moyenne. Deux patients (3,6 %) presentaient des sequelles deux ans apres l’intervention : une douleur residuelle sur la cicatrice et une ossification ectopique indolore en regard du site de prelevement. Discussion La morbidite du prelevement tibial medioproximal est faible. La technique est simple, rapide et sure. L’os spongieux recueilli est suffisant pour greffer deux sites alveolaires simultanement. Ce site nous semble particulierement adapte a l’alveoloplastie secondaire chez l’enfant.

We recently observed a near fatal case of transfusion-transmitted infection with standard platelet concentrate. Streptococcus dysgalactiae subspecies equisimilis was isolated both from donor, residual component container and cultures of the patient's blood. This should question the usefulness of systematic bacterial detection in platelet concentrates, however a lethal accident has occurred recently which escaped bacterial detection. This observation calls for implementation of pathogen inactivation procedures for platelets concentrates.

We describe the characterization of a novel CTX-M β-lactamase from Salmonella enterica . Four S. enterica isolates (three of serotype Westhampton and one of serotype Senftenberg) resistant to extended-spectrum cephalosporins (cefotaxime and ceftazidime) were recovered in 2004 from living cockles in three supermarkets located in distant geographic areas in France, which got their supplies from the same fishery. The isolates were found to produce a novel extended-spectrum β-lactamase (ESBL) belonging to the CTX-M-1 phylogenetic group and named CTX-M-53. The CTX-M-53 β-lactamase harbored the substitution Asp240Gly, like the CTX-M-15 enzyme, which is specifically implicated in a higher catalytic efficiency against ceftazidime. The bla CTX-M-53 gene was located on a mobilizable 11-kb plasmid, pWES-1. The complete sequence of pWES-1 revealed the presence of a novel insertion sequence, IS Sen2 , and an IS 26 element upstream and downstream of the bla CTX-M-53 gene, respectively; however, transposition assays of the bla CTX-M-53 gene were unsuccessful. IS 26 elements may have contributed to the acquisition of the bla CTX-M-53 gene. Interestingly, the mobilization module of the pWES-1 plasmid was similar to that of quinolone resistance plasmids (carrying the qnrS2 gene) from aquatic sources. Although belonging to two serotypes differentiated on the basis of the O-antigen structure (E1 or E4 groups), the isolates were found to be genetically indistinguishable by pulsed-field gel electrophoresis. Multilocus sequence typing showed that the isolates of serotype Westhampton had a sequence type, ST14, common among isolates of serotype Senftenberg. This is the first characterization of the CTX-M-53 ESBL, which represents an additional ceftazidime-hydrolyzing CTX-M enzyme.

Because of the expected significant growth in the elderly population and respiratory diseases, the topic of "delegation of physician's duties" is of increasing importance to the German health-care system. In 2004 the German Respiratory Society (Deutsche Gesellschaft fur Pneumologie und Beatmungsmedizin e. V. (DGP)) established the new profession: respiratory therapist. A curriculum was defined which offers training for certified nurses and physiotherapists. Respiratory therapists evaluate, treat, document and care for patients with pulmonary disorders. Under appropriate supervision a licensed respiratory therapist performs some of the work previously done by physicians at the same quality of care. The first respiratory therapists have finished their professional training in Germany. Most of these respiratory therapists are now employed in hospital-based positions requiring their specific skills. Generally, the increased medical responsibility and the increased degree of decision-making possibilities associated with the new profession contribute to a better job satisfaction. However, this is not yet true for all the newly employed respiratory therapists. Only few of the new graduate respiratory therapists were awarded higher salaries. It is a strongly recommendation to the heads of medical departments and the human resources managers of hospitals that they should recognise the increased qualifications of nurses and physiotherapists who become respiratory therapists by appropriate remuneration.

The aim of the present study was to investigate the efficacy of infliximab for the treatment of extrapulmonary sarcoidosis. A prospective, randomised, double-blind, placebo-controlled trial was conducted, with infliximab at 3 and 5 mg x kg(-1) body weight administered over 24 weeks. Extrapulmonary organ severity was determined by a novel severity tool (extrapulmonary physician organ severity tool; ePOST) with an adjustment for the number of organs involved (ePOSTadj). In total, 138 patients enrolled in the trial of infliximab versus placebo for the treatment of chronic corticosteroid-dependent pulmonary sarcoidosis. The baseline severity of extrapulmonary organ involvement, as measured by ePOST, was similar across treatment groups. After 24 weeks of drug-therapy study, the change from baseline to week 24 in ePOST was greater for the combined infliximab group compared with the placebo group. After adjustment for the number of extrapulmonary organs involved, the improvement in ePOSTadj observed in the combined infliximab group was also greater than that observed in placebo-treated patients, after 24 weeks of therapy. The improvements in ePOST and ePOSTadj were not maintained during a subsequent 24-week washout period. Infliximab may be beneficial compared with placebo in the treatment of extrapulmonary sarcoidosis in patients already receiving corticosteroids, as assessed by the severity tool described in the present study.

Die Spirometrie ist ein hervorragend standardisiertes Messverfahren, mit dem die forcierte Vitalkapazitat (FVC) mit hoher Prazision und Reproduzierbarkeit bestimmt werden kann. Speziell bei Patienten mit idiopathischer pulmonaler Fibrose (IPF) reflektiert die FVC und deren Abfall uber die Zeit den zugrunde liegenden Krankheitsprozess, der durch Vernarbung der Alveolen und Schrumpfung der Lungen charakterisiert ist. Dementsprechend zeigen zahlreiche Studien einen konsistenten Zusammenhang zwischen der Abnahme der FVC im Zeitverlauf und der Mortalitat. Nachdem erstmals wirksame Medikamente zur Therapie der IPF entwickelt wurden, bestatigt sich, dass in Studien, die einen positiven Effekt des Medikaments auf den Abfall der FVC zeigen konnten, auch ein zumindest numerisch positiver Effekt auf die Mortalitat gefunden wurde, wahrend in einer Studie, die keinen signifikanten Effekt auf den Abfall der FVC zeigte, auch die Mortalitat nicht beeinflusst wurde. Insofern kann der Abfall der FVC als Surrogat fur Mortalitat bei IPF-Patienten in prospektiven interventionellen Studien als validiert betrachtet werden. Die FVC-Abnahme ist daher nicht nur ein anerkannter Studienendpunkt, sondern sollte auch fur die Bewertung des patientenrelevanten Nutzens berucksichtigt werden.

Die CT ist nach neoadjuvanter Radio-Chemo-Therapie zur Charakterisierung der Tumorregression nur begrenzt einsetzbar. Daher sollte die Wertigkeit der 18F-FDG-PET als molekulares, nichtinvasives bildgebendes Verfahren analysiert werden. Bislang 32/100 Patienten mit NSCLC Stadium IIIA/IIIB wurden in einer multizentrischen, randomisierten Therapiestudie (LUCAS-MD) untersucht. Pratherapeutisch erfolgten eine 18F-FDG-PET und eine Spiral-CT. Der neoadjuvante Therapieblock bestand aus 2–3 Zyklen Paclitaxel und Carboplatin sowie einer simultanen Radio-Chemo-Therapie. Es folgte eine zweite PET direkt vor der Operation mit Bestimmung des Glukosemetabolismus fur Primartumor und Lymphknotenmetastasen sowie eine PET-CT-Bildfusion. Der am OP-Praparat bestimmte Regressionsgrad wurde mit den PET-Befunden und dem Uberleben der Patienten korreliert. In Lymphknoten von 10 Patienten mit kompletter Remission in der FDG-PET zeigte sich ein Regressionsgrad/RG III im OP-Praparat (Sensitivitat 100%). Zu 94% wiesen die 16/32 Patienten mit kompletter Remission im Primartumor RG IIb oder III auf, ein Patient RG IIa (falsch-negativ). Die Zweijahresuberlebenswahrscheinlichkeit bei kompletter Remission war nach 24 Monaten signifikant erhoht (76 vs. 20%, p=0,0079). Patienten mit RG III bzw. IIb lebten signikant langer als Patienten mit RG IIa bzw. I (63 vs. 36%, p=0,0123). Der RG korreliert mit der in der FDG-PET bestimmten metabolischen Remission. Die PET eilt metabolisch dem durch die CT bestimmten Tumoransprechen nach neoadjuvanter Behandlung deutlich voraus und ermoglicht wahrscheinlich eine prospektive Aussage uber den Langzeittherapieerfolg von Patienten mit NSCLC im Stadium III.

Respiratory therapists are healthcare professionals taking care of patients with pulmonary disorders. They are an allied health specialty, practicing under medical direction. The professionalism of nurses and therapists must grow up to act successfully in new fields of medicine, where evidence-based independent action is necessary. Specialized therapists can help us coordinate separated processes (diagnoses, therapy and nursing). The profession "Respiratory Therapist" was created in the United States 50 years ago. We intend to introduce this profession also in Germany. We follow many other countries who have already taken this step. We hope that we can reach yet a higher quality of patient care.

The production of β-lactamases is the predominant cause of resistance to β-lactam antibiotics in gram-negative bacteria. These enzymes cleave the amide bond in the β-lactam ring, rendering β-lactam antibiotics harmless to bacteria. They are classified according to the scheme of Ambler et al. (2) into four classes, designated classes A to D, on the basis of their amino acid sequences, with classes A and C being the most frequently occurring among bacteria. Oxyimino-cephalosporins such as cefotaxime and ceftazidime, which are inherently less susceptible to β-lactamases, were introduced in the early 1980s to treat infections caused by gram-negative bacilli that were resistant to established β-lactams and that produced class A, C, and D β-lactamases. Their repetitive and increased use induced the appearance of resistant strains, which overproduced class C enzymes (42, 72) and/or which produced extended-spectrum β-lactamases (ESBLs), mainly those of class A but also those of class D (19, 61). Class A ESBLs hydrolyze oxyimino-cephalosporins and aztreonam but not 7-α-substituted β-lactams. They are generally susceptible to β-lactamase inhibitors (clavulanate, sulbactam, tazobactam). According to the functional classification scheme of Bush et al. (23), class A ESBLs are therefore clustered in group 2be, which can be subdivided on the basis of their activities against ceftazidime and cefotaxime as ceftazidimases (higher levels of hydrolytic activity against ceftazidime than against cefotaxime) and cefotaximases (higher levels of hydrolytic activity against cefotaxime than against ceftazidime), respectively (48). However, class A ESBLs form a heterogeneous molecular cluster comprising β-lactamases sharing 20 to >99% identity. The earliest class A ESBLs, which were reported from 1985 to 1987, differed from widespread plasmid-mediated TEM-1/2 and SHV-1 penicillinases by one to four point mutations, which extend their hydrolytic spectra (51, 90, 91). TEM and SVH ESBLs now comprise at least 130 members and have a worldwide distribution. Most of them are ceftazidimases, and only a few are cefotaximases. More recently, non-TEM and non-SHV plasmid-mediated class A ESBLs have been reported: ceftazidimases of the PER, VEB, TLA-1, and GES/IBC types and cefotaximases of the SFO-1, BES-1, and CTX-M types (8, 12, 13, 16, 31, 58, 62, 75, 76, 79, 81, 88, 96). The CTX-M β-lactamases are the most widespread enzymes. They were initially reported in the second half of the 1980s, and their rate of dissemination among bacteria and in most parts of the world has increased dramatically since 1995. This review focuses on the origin, epidemiology, clinical impact, enzymatic properties, and structural relationships of the CTX-M-type ESBLs.

Background: The tumor microenvironment plays a critical role in cancer development, progression, and control. We demonstrated in vitro and in vivo that a bidirectional crosstalk between tumor-associated macrophages and cancer cells via CCR2-CCL2 and CX3CR1-CXCL1 signaling is fundamental for lung cancer growth and metastasis offers new treatment concepts. Aim: Our working hypothesis is to develop a new platform for specific chemokine receptor (CCR2) PET imaging and a range of theranostic applications in lung cancer. For this purpose, we planned to define the CCR2 expression in NSCLC as well as in SCLC, tumor cells as well as immune/inflammatory cells. Material and Methods: This is a multicenter trial with patients from Zentralklinik Bad Berka GmbH (n =100 NSCLC, n=100 SCLC). All patients gave informed consent according to the declaration of Helsinki. FFPE material was available in all cases. CCR2 CXCR4 and CX3CR1 expression was determined by immunohistochemistry with the avidin-biotin-peroxidase-complex. Results: Analyzing 96 NSCLC (47 adenocarcinoma, 49 squamous cell carcinoma) and 45 SCLC tumor samples, we found CXCR4 and CCR2 chemokine receptor expression in tumor, immune and inflammatory cells. In NSCLC, co-expression between CCR2 and CXCR4 staining was very high concerning their expression on tumor cells rising with higher tumor stages, proliferation rate and grading. CCR2 expression in immune cells was restricted to lower stages; the same pattern could be observed in 45 SCLC tumor samples where CCR2 expression on immune cells was found especially in limited disease rather than in metastatic disease; CXCR4 expression in tumor cells was found to be high in all stages of SCLC. To evaluate the therapeutic efficacy of CCR2 antagonism in vivo, we injected LLC1 s.c. into WT mice treated with CCR2 antagonist (RS504393) or vehicle. Notably, tumor growth was significantly inhibited in CCR2 antagonist-treated mice as compared with vehicle-treated mice. Discussion: Our preliminary results show a significant portion of CCR2 positive tumors - NSCLC as well as SCLC which would qualify for a CCR2-based imaging as well as - demonstrated in our mice models - CCR2 inhibitory strategies. This should be evaluated in further preclinical trials. Citation Format: Katalin Nagy-Major, Jörg Sänger, Harshad R. Kulkarni, Peter Fix, Almut Kunze, Amelie Lupp, Reiner Bonnet, Werner Seeger, Richard P. Baum, Patricia Grabowski, Rajkumar Savai. Chemokine receptor signaling as a new tool to improve lung cancer diagnostics and therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 944. doi:10.1158/1538-7445.AM2017-944

OBJECTIVE: Although radiation therapy is used in early-stage inoperable lung cancer, it often results in injury to functional lung tissue. A study was undertaken to determine the frequency and severity of pulmonary injury revealed by CT in patients who had undergone conformal proton (to a limited volume) radiation therapy. We compared these findings with those from a group of patients who had undergone a combination of photon and conformal proton (to a larger volume) radiation therapy. CONCLUSION: Proton radiation therapy was associated with a lower frequency of pulmonary injury than the combined regimen. Injury correlated well with the volume of normal lung that was irradiated. Conformal proton radiation therapy appears to be able to reduce the incidence and severity of pulmonary injury revealed by CT.

Die idiopathische pulmonale Fibrose (IPF) ist eine schwerwiegende und in der Regel zum Tod fuhrende Erkrankung, die bisher nur unzureichend behandelt werden kann. Empfehlungen zur Diagnostik und Therapie wurden erstmals im ATS-ERS-Statement im Jahr 2000 publiziert 1 . Seither haben sich die diagnostischen Standards geandert und es liegen zahlreiche Therapiestudien zu diesem Krankheitsbild vor, die es erforderlich machten, die bestehenden Empfehlungen zu uberarbeiten und eine wissenschaftlich begrundete Leitlinie zu erstellen. Diese wurde von einer internationalen Expertengruppe in den Jahren 2006 – 2010 erarbeitet und publiziert 2 . Die folgenden Ausfuhrungen beinhalten eine Ubersetzung wesentlicher Inhalte der Originalleitlinie sowie die Interpretation und Adaptation der Empfehlungen an die speziellen Belange des deutschen Gesundheitssystems, wobei auch neue wissenschaftliche Erkenntnisse Berucksichtigung fanden. Die Deutsche Leitlinie zur Diagnostik und Therapie der IPF beruht auf einer Initiative deutscher Experten unter der Schirmherrschaft der Deutschen Gesellschaft fur Pneumologie und Beatmungsmedizin (DGP) und auf den Ergebnissen einer Konsensuskonferenz, die am 3. 12. 2011 in Bochum unter Supervision der „Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF)“ abgehalten wurde. Die Mehrzahl der Empfehlungen der internationalen Leitlinie konnten dabei ubernommen werden. Basierend auf aktuellen Studienergebnissen, die zum Zeitpunkt der Verabschiedung der internationalen Leitlinie noch nicht bzw. nicht vollstandig vorlagen wurden die schwach negativen Empfehlungen fur die Antikoagulantientherapie und die Kombinationstherapie mit Prednison, Azathioprin und N-Acteylcystein in stark negative Empfehlungen umgewandelt, wahrend fur Pirfenidon, welches inzwischen in der Europaischen Union zugelassen ist, eine schwach positive Therapieempfehlung ausgesprochen wurde.

Therapy and course of pulmonary manifestations of carcinosarcomas in three patients are described. For this rare mixed tumor there is a prevalence among men between the ages of forty and seventy. Operative therapy should be employed whenever possible, because of the poor results achieved thus far using radiotherapy or chemotherapy. Carcinosarcomas were thought to have a worse prognosis than other non-small-cell bronchial carcinomas but an increasing number of reports indicate a similar clinical course and prognosis. Pneumonectomy was required for two of our patients and lobectomy was performed in the third. The period of observation extended over two years. One patient, tumor stage T4N0M0 died of his disease after seven months. The two other patients, tumor stages T3N0M0 and T2N1M0, were operated on thirty-three and thirty-five months ago respectively and are clinically disease-free and in good health.

Background: This report summarizes initial tests of an emphysematous lung synthetic polymer sealant (ELS) designed to reduce lung volume in patients with advanced emphysema. Objectives: The primary study objective was to define a therapeutic strategy to optimize treatment safety and effectiveness. Methods: ELS therapy was administered bronchoscopically to 25 patients with heterogeneous emphysema in an open-label, noncontrolled study at 6 centers in Germany. Treatment was performed initially at 2–4 subsegments. After 12 weeks, patients were eligible for repeat therapy to a total of 6 sites. Safety and efficacy were assessed after 6 months. Responses were evaluated in terms of changes from baseline in lung physiology, functional capacity, and health-related quality of life. Follow-up is available for 21 of 25 patients. Results: Treatment was well tolerated. There were no treatment-related deaths (i.e. within 90 days of treatment), and an acceptable short- and long-term safety profile. Physiological and clinical benefits were observed at 24 weeks. Efficacy responses were better among Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage III patients [n = 14; change in residual volume/total lung capacity (ΔRV/TLC) = –7.4 ± 10.3%; Δ forced expiratory volume in 1 s (ΔFEV1) = +15.9 ± 22.6%; change in forced vital capacity (ΔFVC) = +24.1 ± 22.7%; change in carbon monoxide lung diffusion capacity (ΔDLCO) = +19.3 ± 34.8%; change in 6-min walk test (Δ6MWD) = +28.7 ± 59.6 m; change in Medical Research Council Dyspnea (ΔMRCD) score = –1.0 ± 1.04 units; change in St. George’s Respiratory Questionnaire (ΔSGRQ) score = –9.9 ± 15.3 units] than for GOLD stage IV patients (n = 7; ΔRV/TLC = –0.5 ± 6.4%; ΔFEV1 = +2.3 ± 12.3%; ΔFVC = +2.6 ± 21.1%; ΔDLCO = –2.8 ± 17.2%; Δ6MWD = +28.3 ± 58.4 m; ΔMRCD = 0.3 ± 0.81 units; ΔSGRQ = –6.7 ± 7.0 units). Conclusions: ELS therapy shows promise for treating patients with advanced heterogeneous emphysema. Additional studies to assess responses in a larger cohort with a longer follow-up are warranted.

Pseudomonas luteola (formerly classified as CDC group Ve-1 and named Chryseomonas luteola ) is an unusual pathogen implicated in rare but serious infections in humans. A novel β-lactamase gene, bla LUT-1 , was cloned from the whole-cell DNA of the P. luteola clinical isolate LAM, which had a weak narrow-spectrum β-lactam-resistant phenotype, and expressed in Escherichia coli . This gene encoded LUT-1, a 296-amino-acid Ambler class A β-lactamase with a pI of 6 and a theoretical molecular mass of 28.9 kDa. The catalytic efficiency of this enzyme was higher for cephalothin, cefuroxime, and cefotaxime than for penicillins. It was found to be 49% to 59% identical to other Ambler class A β-lactamases from Burkholderia sp. (PenA to PenL), Ralstonia eutropha (REUT), Citrobacter sedlakii (SED-1), Serratia fonticola (FONA and SFC-1), Klebsiella sp. (KPC and OXY), and CTX-M extended-spectrum β-lactamases. No gene homologous to the regulatory ampR genes of class A β-lactamases was found in the vicinity of the bla LUT-1 gene. The entire bla LUT-1 coding region was amplified by PCR and sequenced in five other genetically unrelated P. luteola strains (including the P. luteola type strain). A new variant of bla LUT-1 was found for each strain. These genes (named bla LUT-2 to bla LUT-6 ) had nucleotide sequences 98.1 to 99.5% identical to that of bla LUT-1 and differing from this gene by two to four nonsynonymous single nucleotide polymorphisms. The bla LUT gene was located on a 700- to 800-kb chromosomal I-CeuI fragment, the precise size of this fragment depending on the P. luteola strain.

This paper describes an outbreak of Pseudomonas aeruginosa and Pseudomonas putida that occurred in an oncohaematology paediatric unit between January and April 2005. Eight children had nosocomial infections due to P. aeruginosa (N=5) or P. putida (N=3), which were recovered from central venous catheter blood cultures (N=4), the catheter exit site alone (N=2), or the catheter exit site and the catheter tip (N=2). Subsequent investigation showed that contaminated water outlets represented the possible source of spread. Studies of nursing and environmental cleaning practices revealed two modes of catheter contamination. A reduction in the size of the catheter dressing at the exit site gave less protective cover during showers, and a detergent-disinfectant diluted with tap water had contaminated perfusion bottles. Repetitive intergenic consensus polymerase chain reaction indicated two discrete patterns for P. aeruginosa and one for P. putida. The water network was chlorinated, and disposable seven-day filters were fitted on all taps and showers. Due to the deleterious effects of chlorination on the water network and the cost of the weekly filter change, a water loop producing microbiologically controlled water was installed. In addition, the concentration of the detergent-disinfectant was increased and refillable sprayers were replaced with ready-to-use detergent-disinfectant solution for high-risk areas. Following these measures, no Pseudomonas spp. have since been isolated in clinical or environmental samples from the ward.

Bacterial expression of beta-lactamases is the most widespread resistance mechanism to beta-lactam antibiotics, such as penicillins and cephalosporins. There is a pressing need for novel, non-beta-lactam inhibitors of these enzymes. One previously discovered novel inhibitor of the beta-lactamase AmpC, compound 1, has several favorable properties: it is chemically dissimilar to beta-lactams and is a noncovalent, competitive inhibitor of the enzyme. However, at 26 microM its activity is modest. Using the X-ray structure of the AmpC/1 complex as a template, 14 analogues were designed and synthesized. The most active of these, compound 10, had a K(i) of 1 microM, 26-fold better than the lead. To understand the origins of this improved activity, the structures of AmpC in complex with compound 10 and an analogue, compound 11, were determined by X-ray crystallography to 1.97 and 1.96 A, respectively. Compound 10 was active in cell culture, reversing resistance to the third generation cephalosporin ceftazidime in bacterial pathogens expressing AmpC. In contrast to beta-lactam-based inhibitors clavulanate and cefoxitin, compound 10 did not up-regulate beta-lactamase expression in cell culture but simply inhibited the enzyme expressed by the resistant bacteria. Its escape from this resistance mechanism derives from its dissimilarity to beta-lactam antibiotics.

The natural beta-carbolines (BC) closely resemble the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in structure. The N-methylated beta-carbolinium ions (BC+) are potent inhibitors of mitochondrial respiration and are nigrostriatal neurotoxins. Utilizing [3H]BC, we have identified several proteins to which BC binds with high affinity (e.g. the chaperone member glucose regulated protein 78, the enzyme carboxylesterase, the cytochrome P450 2E1, the enzyme monoamine oxidase B and a small G-protein of the Rho subfamily). In the present study we isolated a protein from bovine brain to which [3H]BC binds with high affinity and identified it being the enzyme triosephosphate isomerase (TPI; EC 5.3.1.1.). 2,9-Dimethyl-BC+ was the most potent inhibitor of TPI, clearly more potent than the known inhibitors. TPI deficiency is a rare disorder in humans characterized by a severe progressive extrapyramidal course. Thus, TPI inhibition could contribute to neurodegeneration observed after injection of BCs into substantia nigra. Furthermore, the findings fit into the hypothesis of BCs as endogenous toxins responsible for neurodegeneration.

A prospective analysis was performed in 124 non-small cell lung cancer patients to determine the role of F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) for molecular (metabolic) staging (n=63), therapy monitoring after induction-chemotherapy (n=34), and conformai radiation treatment planning (n=27). Staging by FDG-PET was significantly more accurate than CT (p

Objectives To study the sensibility (Se) and specificity (Sp) of clinical and biological signs for the diagnosis of septic arthritis (SA). Methods This prospective study included all adult patients with a suspicion of SA seen in the emergency department or rheumatology service at the University Hospital of Clermont-Ferrand during a period of 18 months. The sensibility and specificity of the clinical and biological signs for the diagnosis of SA were calculated. A univariate analysis followed by a logistic regression analysis for SA diagnosis was conducted. Results In total, 105 patients with a suspected SA were included, 38 (36%) presenting with SA (29 with a bacteriologically documented SA). In univariate analysis, chills (Se 39%; Sp 82%, p=0.015) but not fever (Se 53%; Sp 53%, p=0.6), a slow onset duration (Se 54%; Sp 72%, p=0.04), local redness (Se 53%, Sp 72%, p=0.01), as well as an infection entry-site (Se 7%; Sp 54%, p=0.01) were found most often in the SA cases. Microcrystalline antecedents (Se 5%, Sp 72%, 95% CI 0-0.6) and involvement of the knee were more frequent in non-septic arthritis (non-SA) cases. An erythrocyte sedimentation rate (ESR) >50 mm (Se 72%; Sp 60%, p=0.005), a C-reactive protein level >100mg/L (Se 58%; Sp 66%, p=0.019) and, above all, suggestive radiological signs (Se 30%; Sp 95%, p=0.001) were more frequent in the SA cases. The clear (Se 0; Sp 81%, p=0.007) and purulent (Se 57%, Sp 88, p 50000/μL (Se 57%; Sp 82%, p 90% (Se 42%; Sp 82%, p=0.02), but not the presence of microcrystals (Se 24%, Sp 58% p=0.09). In multivariate analysis, only chills (OR=4.1, 95% CI: 1.4-12.2), microcrystalline antecedents (OR=0.08, 95% CI: 0.01-0.5), and radiological signs (OR=11, 95% CI: 2.4-50.1) remained significant. The parameters chills, microcrystalline antecedents, infection entry-site, risk factors for SA, the aspect and cellularity of synovial fluid, and radiological signs permitted the elaboration of two logistic regression models for the diagnosis of SA (AUC: 0.85 and 0.87). Conclusions No clinical or biological (excluding bacteriological) sign, taken alone, is conclusive for the differentiation between SA and non-SA pathology, but the association of several signs, notably chills, microcrystalline antecedents, radiological signs of SA, and the aspect and cellularity of joint liquid may be conclusive. Disclosure of Interest None Declared

In spite of modern suture material and stapler technique, postoperative bronchial stump fistulas are still serious complications. Besides rethoracotomy, which carries a high risk in these seriously ill patients, sealing of the fistula by endoscopic techniques has developed as a new method of treatment. Retrospectively we analyzed the data of all patients with a fistula from January 1989 to April 1992. One fistula following lobectomy was permanently closed by a single application of fibrin glue. Two early fistulas after pneumonectomy were immediately closed by rethoracotomy. Of nine fistulas (or stump necroses) seven could be cured by fibrin application alone or in combination with spongy bone implantation. Two patients were treated by rethoracotomy.

To determine the characteristics and reproducibility of circadian rhythms of airway responsiveness to histamine and methacholine and their relationship to airway tone in patients with mild asthma, we studied nine subjects with complaints of nighttime awakening due to dyspnea and/or cough at least once a week. Their mean age was 31.4 yr (range 17–65) and their mean daytime FEV1 was 99 +/- 14 (SD) % predicted. Forced expiratory volume in 1 s (FEV1) and the provocative concentrations of histamine and methacholine necessary to decrease FEV1 by 20% (PC20FEV1) were determined every 4 h for 13 consecutive measurements. Three subjects were measured with histamine, three with methacholine, and three with both histamine and methacholine. Data were evaluated on an individual basis. PC20FEV1 to histamine and methacholine showed significant and reproducible circadian variations in all cases (P less than 0.01 each) with a mean amplitude of 1.00 +/- 0.17 (SD) doubling concentrations for histamine and 1.35 +/- 0.29 doubling concentrations for methacholine. The amplitude of PC20FEV1 was significantly larger (P less than 0.05) and the time of maximum responsiveness was significantly earlier (P less than 0.05) with methacholine compared with histamine. FEV1 showed significant (P less than 0.05) circadian variations in three of nine subjects, and peak expiratory flow rate showed variations in two subjects. Correlation between the variations of FEV1 and PC20FEV1 was significant (P less than 0.05) in 5 of 12 cases.(ABSTRACT TRUNCATED AT 250 WORDS)