Purpose Lower serum vitamin D levels have been associated with an increased risk of aggressive prostate cancer. Among men with localized prostate cancer, especially with low-or intermediate-risk disease, vitamin D may serve as an important biomarker of disease aggression. The aim of this study was to assess the relationship between adverse pathology at the time of radical prostatectomy and serum 25-hydroxyvitamin D (25-OH D) levels. Methods This cross-sectional study was carried out from 2009 to 2014, nested within a large epidemiologic study of 1,760 healthy controls and men undergoing prostate cancer screening. In total, 190 men underwent radical prostatectomy in the cohort. Adverse pathology was defined as the presence of primary Gleason 4 or any Gleason 5 disease, or extraprostatic extension. Descriptive and multivariate analyses were performed to assess the relationship between 25-OH D and adverse pathology at the time of prostatectomy. Results Eighty-seven men (45.8%) in this cohort demonstrated adverse pathology at radical prostatectomy. The median age in the cohort was 64.0 years (interquartile range, 59.0 to 67.0). On univariate analysis, men with adverse pathology at radical prostatectomy demonstrated lower median serum 25-OH D (22.7 v 27.0 ng/mL, P = .007) compared with their counterparts. On multivariate analysis, controlling for age, serum prostate specific antigen, and abnormal digital rectal examination, serum 25-OH D less than 30 ng/mL was associated with increased odds of adverse pathology (odds ratio, 2.64; 95% CI, 1.25 to 5.59; P = .01). Conclusion Insufficiency/deficiency of serum 25-OH D is associated with increased odds of adverse pathology in men with localized disease undergoing radical prostatectomy. Serum 25-OH D may serve as a useful biomarker in prostate cancer aggressiveness, which deserves continued study. (C) 2016 by American Society of Clinical Oncology

Le cancer de prostate (CaP) est le plus fréquent chez l’homme de plus de 50 ans. La généralisation du PSA et du dépistage du CaP a permis son diagnostic à des formes localisées (80% des formes diagnostiquées), accessibles à un traitement curatif. De plus, un certain nombre de ces formes localisées sont indolentes, de très faible risque, éligibles à une surveillance active (SA).Cependant, 15 à 25% des patients vont présenter une récidive 10 ans après un traitement curatif, et environ 30% des patients inclus en SA seraient en fait sous-évalués (cancer significatif). Il est donc nécessaire d’identifier de nouveaux biomarqueurs pronostiques capables de distinguer les tumeurs indolentes des tumeurs à haut risque, et capables d’améliorer la prédiction du risque de récidive après traitement curatif. Objectifs : Evaluer la valeur pronostique potentielle du remodelage de la signalisation calcique dans le cancer de prostate : 1) Evaluer le lien entre remodelage de la signalisation calcique et agressivité tumorale 2) Evaluer l’impact pronostique du remodelage de la signalisation calcique sur la récidive systémique après prostatectomie radicale(PR). 3) Evaluer l’apport du remodelage de la signalisation calcique dans la sélection des patients éligibles à la surveillance active. Méthodologie 1) Evaluation de l’expression (immunohistochimie) de TRPC1, TRPC4, Orai1 et STIM1 à différents stades de progression du CaP, et évaluation de l’impact pronostique de cette expression sur la récidive dans le CaP localisé à partir d’une cohorte de 238 patients. 2) Etude cas-témoin à partir d’une cohorte de 112 patients opérés d’un CaP localisé. Evaluation de l’impact pronostique de l’expression (immunohistochimie) de 10 acteurs de la signalisation calcique (Orai1, Orai2, Orai3, STIM1, STIM2, TRPV5 et V6, TRPC1 et C4, TRPM8) sur la récidive systémique après PR. 3). A partir d’une cohorte de patients ayant été opérés pour des cancers de faible risque, ont été inclus les patients potentiellement éligibles à une SA au moment du diagnostic (n=71). Etude de l’apport de la signalisation calcique dans la sélection des patients éligibles à la SA (marquage immunohistochimie sur biopsies et pièce opératoire : TRPC1 et C4, TRPV5 et V6, Orai1, STIM1) Résultats 1) Dans le Cap localisé, une surexpression de TRPC1 était associée à une prolifération plus faible et une meilleure survie sans récidive (indépendant des marqueurs pronostiques usuels). 2) Une surexpression de TRPC4, TRPV5 et TRPV6 est associée à un plus faible risque de récidive systémique après prostatectomie, et ce indépendamment des 5 facteurs pronostiques usuels. 3) Un marquage plus intense de TRPV6 sur les biopsies prostatiques semble associé à un CaP significatif, éligible à un traitement curatif d’emblée chez les patients présentant un CaP de faible risque. Conclusion : Sur pièce de PR, TRPC1, TRPC4, TRPV5 et TRPV6 possèdent une valeur pronostique indépendante et sont associés à un plus faible risque de récidive après PR. Sur biopsie prostatique, TRPV6 permet de distinguer les CaP indolents des significatifs chez les patients présentant un CaP de faible risque. / Prostate cancer (PCa) is the most common malignancy in men 50 years and older and the second leading cause of cancerrelated death in men in developed countries. Widespread PSA screening has allowed an increase rate of localised PCa at diagnosis, managed by curative treatment such as radical prostatectomy (RP), or active surveillance (AS) in case of indolent disease. However, 30% of patients experience biochemical relapse during the 10 years following RP. Moreover, 30% of patients in AS are undervalued and present a significant disease. It is therefore necessary to identify new prognostic biomarkers capable of distinguishing indolent from significant tumours, and capable to accurately predict the risk of recurrence after curative treatment. Objectives: To evaluate the potential prognostic value of calcium signalling remodeling in PCa: 1) To assess the impact of calcium signalling remodelling on tumour aggressiveness 2) To assess the prognostic value of calcium signalling remodelling on systemic recurrence after RP. 3) To assess the contribution of calcium signaling remodelling in the selection of patients for active surveillance (AS). Methods 1) Study of the expression (immunohistochemistry) of TRPC1, TRPC4, Orai1 and STIM1 at different stages of PCa, and assessment of the prognostic value of this expression on recurrence in clinically localised PCa (CLC) in a cohort of 238 patients. 2) Case-control study on a cohort of 112 patients who underwent RP for CLC. Evaluation of the prognostic impact of the expression (immunohistochemistry) of 10 actors of calcium signalling (Orai1, Orai2, Orai3, STIM1, STIM2, TRPV5 and V6, TRPC1 and C4, TRPM8) on systemic recurrence after RP. 3) From a cohort of patients who underwent RP for low-risk PCa, were enrolled patients potentially eligible for AS at the time of diagnosis (n = 71). We evaluated the impact of calcium signalling remodelling in patients selection for AS (immunohistochemical staining on biopsies and prostate specimens: TRPC1 and C4, TRPV5 and V6, Orai1, STIM1).Results 1) In CLC, an overexpression of TRPC1 was associated with a decreased proliferation, and with a higher rate of biochemical progression-free survival (independent of usual prognostic markers). 2) Overexpression of TRPC4, TRPV5 and TRPV6 was associated with a lower risk of systemic recurrence after RP, independently of the prognostic factors currently used. 3) More intense staining of TRPV6 on biopsies was associated with a significant PCa, for which a curative treatment is required. Conclusion: On RP specimens, overexpression of TRPC1, TRPC4, TRPV5 and TRPV6 has an independent prognostic value and is associated with a lower risk of recurrence after RP. On prostate biopsies, TRPV6 allows to distinguish indolent from significant disease in patients with low-risk PCa.

L’IRM représente une modalité d’imagerie du cancer de la prostate qui occupe une place de plus en plus importante pour le diagnostic positif. D’autres indications sont en cours de validation pour établir le pronostique, pour guider le traitement et pour assurer le suivi après traitement notamment partiel. La première partie de ce travail a porté sur les études cliniques de l’IRM dans la sélection des candidats à une surveillance active. Les performances de l’IRM particulièrement dans la détection des cancers antérieurs permettront de réduire le risque de sous-estimation initiale des tumeurs et par conséquent le risque de la reclassification au cours des protocoles de surveillance active. La seconde partie de ce travail a porté sur la corrélation entre les anomalies de signal à l’IRM et les zones tumorales et non tumorales intra-prostatiques. La validation d’une technique simple et reproductible de recalage a permis ensuite une corrélation des anomalies de signal enregistrées sur l’IRM et des paramètres histo-pathologiques quantitatifs des pièces opératoires de prostatectomie. / MRI is an increasingly important imaging modality for prostate cancer diagnosis. Further indications are being validated in prostate cancer to establish the prognostic, to guide treatment and to follow up patients especially after partial treatment. The first part of this work has focused on clinical studies of MRI in patient selection for active surveillance. The performance of MRI particularly in the detection of anterior cancers would reduce the risk of initial underestimation of tumor burden and therefore reduce the risk of reclassification during active surveillance protocols. The second part of this work has focused on the correlation between the signal abnormalities on MRI and intra-prostatic areas. We used a simple and reproducible technique for MRI and histopathology registration and we correlated signal abnormalities recorded on MRI with quantitative histopathological parameters at prostatectomy surgical specimens.

303 gesunde, deutsche Freiwillige, die in 53 verschiedene Länder (meist nach Asien, Afrika und Südamerika) reisten, wurden in eine prospektive Kohortenstudie aufgenommen. Stuhlproben und Daten über potenzielle reiseassoziierte Risikofaktoren (wie Reisestil, Essgewohnheiten, Auftreten von Gastroenteritis, Hygienemaßnahmen) wurden vor und nach der Reise mittels Fragebogen gesammelt. Mittels Selektivmedien (CHROMagar™ ESBL/KPC-Platten) wurden eine Untersuchung der Stuhlproben auf extended-spectrum beta-lactamase bildende Enterobacteriaceae (ESBL-PE) und Carbapenemase bildende Enterobacteriaceae (CPE) durchgeführt. Isolate mit bestätigtem ESBL-Phänotyp wurden auf das Vorhandensein von blaCTX-M-, blaTEM-, blaSHV-, blaVIM-, blaNDM-, blaKPC- und blaOXA-48-Genen mit Hilfe von PCR-Amplifikation und -Sequenzierung getestet. Bei den Antibiotikaempfindlichkeitstests wurde mit konventioneller Mikrobouillonverdünnung gearbeitet. Die Auswertung von 205 kompletten Teilnahmen zeigte vor Reiseantritt eine ESBL-PE Prävalenzrate von 6,8% (14/205). Unter den 191 Teilnehmern, die vor der Reise ESBL-negativ getestet wurden, waren nach Reiserückkehr 58 (30,4%) mit ESBL-bildenden Escherichia coli kolonisiert und 5 Reisende (8,6%) waren zusätzlich mit ESBL-produzierenden Klebsiella pneumoniae besiedelt. Carbapenem-resistente Enterobacteriaceae wurden nicht nachgewiesen. Die molekulargenetische ESBL-Typisierung zeigte, dass 52/54 (96,6%) der E. coli und 4/4 (100%) der K. pneumoniae-Stämme, die für die Sequenzierung verfügbar waren, CTX-M-Enzyme produzierten, und zwar überwiegend CTX-M-15 (33/56, 58,9%), und 2/54 (3,7%) der E. coli-Stämme SHV-12-Enzyme bildeten. Die Reisenden nach Indien wiesen die höchste Kolonisationsrate mit ESBL-PE (11/15, 73,3%: p=0.015) auf, gefolgt von Reisenden nach Südostasien (22/46, 47,8%; p=0.038). Die Auswertung der reiseassoziierten Risikofaktoren ergab allein für das Auftreten einer Gastroenteritis eine statistische Signifikanz (p=0.011). Strikte Händehygiene und ausschließliches Konsumieren abgepackter Getränke zeigten keinen protektiven Effekt. Die ESBL-PE-Persistenzrate nach 6 Monaten lag bei 8,6% (3/35). Daraus schlossen wir, dass weltweite Anstrengungen notwendig sind, um die weitere Ausbreitung von ESBL-PE in der Bevölkerung anzugehen. Eine aktive Überwachung und Kontaktisolation ist bei Aufnahme in eine medizinische Einrichtung speziell für Patienten, die innerhalb der letzten 6 Monate nach Indien und Südostasien gereist waren, empfehlenswert.

Introdução: As reações adversas a medicamentos (RAM) seguem constituindo um problema importante dentro do âmbito hospitalar. Na clínica médica, as reações adversas apresentam-se com alta frequência, pois os pacientes recebem maior número de medicamentos e apresentam maior número de comorbidades. Portanto, são necessárias abordagens que permitam a detecção precoce dos eventos, de maneira que possam ser propostas intervenções que minimizem o dano ao paciente. A busca ativa de rastreadores, sendo estes, resultados alterados de exames laboratoriais, administração de medicamentos específicos e certos acontecimentos, tem se mostrado aplicável e efetiva para o monitoramento das reações adversas a medicamentos. Objetivo: Identificar reações adversas a medicamentos na enfermaria da Clínica Médica de um hospital de nível secundário a partir de rastreadores. Métodos: Desenvolveu-se um estudo de coorte prospectiva na clínica médica do Hospital Universitário da Universidade de São Paulo, sendo utilizada uma lista de 34 rastreadores. Pacientes maiores de 15 anos que permaneceram no mínimo 24 horas na enfermaria foram aleatorizados para compor a amostra. Em cada caso, foram coletadas, de forma cronológica, informações relacionadas aos medicamentos administrados, resultados de exames laboratoriais e a evolução médica. Todos os prontuários foram discutidos por profissionais de saúde, sendo avaliada a causalidade e a gravidade. Realizou-se uma análise univariada comparando pacientes com e sem RAM. Adicionalmente estudou-se o desempenho dos rastreadores usados. Resultados: No período de agosto de 2015 até abril de 2016 foram monitorados 116 pacientes. Identificaram-se reações adversas a medicamentos em 37,9 por cento dos pacientes, sendo achadas 47 suspeitas de RAM em cada 1000 paciente-dia. Pacientes que apresentaram RAMs foram internados mais vezes em leitos classificados como alta-dependência, apresentaram maior duração da internação, maior número de medicamentos usados e menor grau de escolaridade. Em relação ao nível de gravidade, a maioria das suspeitas de RAM (49 eventos, 89,1 por cento ) foram classificadas como moderadas e afetaram o sistema gastrointestinal. Foram identificados 429 rastreadores. Os rastreadores que apresentaram melhor desempenho foram menção da hipotensão, diminuição de plaquetas maior que 50 por cento , administração de glicose hipertônica em 25 ou 50 por cento e suspensão abrupta da medicação. Conclusão: A aplicação prospectiva do método de rastreadores a uma coorte aberta de pacientes da clínica médica permitiu a identificação de suspeitas de reações adversas, a caracterização dos pacientes, as suspeitas, os medicamentos envolvidos e o desempenho dos rastreadores. / Introduction: Adverse drug reactions (ADRs) continues to represent a major problem at hospitals. In internal medicine wards, adverse drug reactions present high frequencies, as patients receive more medicines and have higher number of comorbidities. Therefore, approaches are needed that allow early detection of events, so, interventions could be proposed to minimize harm to patients. The active surveillance using triggers, which are, abnormal laboratory values, administration of specific drugs and certain events, has been proven applicable and effective for monitoring adverse drug reactions. Objective: To identify adverse drug reactions in the internal medicine ward of a secondary university hospital using triggers. Methods: a prospective cohort study was developed in the teaching hospital of the University of São Paulo, using a list of 34 sentinel words. Patients aged 15 years or more, who were hospitalized at least 24 hours, were randomized for the sample. For each case, information related to administered drugs, laboratory results and progress notes were collected chronologically. All charts were discussed by health professionals, assessing causality and severity. A univariate analysis was developed comparing patients with and without ADRs. Additionally, the performance of each trigger was studied. Results: In the period from August 2015 to April 2016, 116 patients were monitored. Adverse drug reactions were identified in 37.9 per cent of patients, presenting a rate of 47 suspected ADRs per 1,000 patient-days. Patients who experience ADRs were frequently classified as nursing high dependency, had longer length of stay, lower education level and used larger number of medicines. Regarding to severity, most of the suspected ADRs (49 cases, 89.1 per cent ) was classified as mild and affected the gastrointestinal system. 429 triggers were identified. Triggers with high performances were \"mention of hypotension\", \"platelets decrease greater than 50 per cent ,\" \"administration of dextrose 25 or 50 per cent \" and \"abrupt medication stop\". Conclusion: The prospective surveillance using triggers in an open cohort of internal medicine inpatients allowed the identification of adverse drug reactions and the characterization of patients, drugs involved and triggers.

Introdução: As reações adversas a medicamentos (RAM) seguem constituindo um problema importante dentro do âmbito hospitalar. Na clínica médica, as reações adversas apresentam-se com alta frequência, pois os pacientes recebem maior número de medicamentos e apresentam maior número de comorbidades. Portanto, são necessárias abordagens que permitam a detecção precoce dos eventos, de maneira que possam ser propostas intervenções que minimizem o dano ao paciente. A busca ativa de rastreadores, sendo estes, resultados alterados de exames laboratoriais, administração de medicamentos específicos e certos acontecimentos, tem se mostrado aplicável e efetiva para o monitoramento das reações adversas a medicamentos. Objetivo: Identificar reações adversas a medicamentos na enfermaria da Clínica Médica de um hospital de nível secundário a partir de rastreadores. Métodos: Desenvolveu-se um estudo de coorte prospectiva na clínica médica do Hospital Universitário da Universidade de São Paulo, sendo utilizada uma lista de 34 rastreadores. Pacientes maiores de 15 anos que permaneceram no mínimo 24 horas na enfermaria foram aleatorizados para compor a amostra. Em cada caso, foram coletadas, de forma cronológica, informações relacionadas aos medicamentos administrados, resultados de exames laboratoriais e a evolução médica. Todos os prontuários foram discutidos por profissionais de saúde, sendo avaliada a causalidade e a gravidade. Realizou-se uma análise univariada comparando pacientes com e sem RAM. Adicionalmente estudou-se o desempenho dos rastreadores usados. Resultados: No período de agosto de 2015 até abril de 2016 foram monitorados 116 pacientes. Identificaram-se reações adversas a medicamentos em 37,9 por cento dos pacientes, sendo achadas 47 suspeitas de RAM em cada 1000 paciente-dia. Pacientes que apresentaram RAMs foram internados mais vezes em leitos classificados como alta-dependência, apresentaram maior duração da internação, maior número de medicamentos usados e menor grau de escolaridade. Em relação ao nível de gravidade, a maioria das suspeitas de RAM (49 eventos, 89,1 por cento ) foram classificadas como moderadas e afetaram o sistema gastrointestinal. Foram identificados 429 rastreadores. Os rastreadores que apresentaram melhor desempenho foram menção da hipotensão, diminuição de plaquetas maior que 50 por cento , administração de glicose hipertônica em 25 ou 50 por cento e suspensão abrupta da medicação. Conclusão: A aplicação prospectiva do método de rastreadores a uma coorte aberta de pacientes da clínica médica permitiu a identificação de suspeitas de reações adversas, a caracterização dos pacientes, as suspeitas, os medicamentos envolvidos e o desempenho dos rastreadores. / Introduction: Adverse drug reactions (ADRs) continues to represent a major problem at hospitals. In internal medicine wards, adverse drug reactions present high frequencies, as patients receive more medicines and have higher number of comorbidities. Therefore, approaches are needed that allow early detection of events, so, interventions could be proposed to minimize harm to patients. The active surveillance using triggers, which are, abnormal laboratory values, administration of specific drugs and certain events, has been proven applicable and effective for monitoring adverse drug reactions. Objective: To identify adverse drug reactions in the internal medicine ward of a secondary university hospital using triggers. Methods: a prospective cohort study was developed in the teaching hospital of the University of São Paulo, using a list of 34 sentinel words. Patients aged 15 years or more, who were hospitalized at least 24 hours, were randomized for the sample. For each case, information related to administered drugs, laboratory results and progress notes were collected chronologically. All charts were discussed by health professionals, assessing causality and severity. A univariate analysis was developed comparing patients with and without ADRs. Additionally, the performance of each trigger was studied. Results: In the period from August 2015 to April 2016, 116 patients were monitored. Adverse drug reactions were identified in 37.9 per cent of patients, presenting a rate of 47 suspected ADRs per 1,000 patient-days. Patients who experience ADRs were frequently classified as nursing high dependency, had longer length of stay, lower education level and used larger number of medicines. Regarding to severity, most of the suspected ADRs (49 cases, 89.1 per cent ) was classified as mild and affected the gastrointestinal system. 429 triggers were identified. Triggers with high performances were \"mention of hypotension\", \"platelets decrease greater than 50 per cent ,\" \"administration of dextrose 25 or 50 per cent \" and \"abrupt medication stop\". Conclusion: The prospective surveillance using triggers in an open cohort of internal medicine inpatients allowed the identification of adverse drug reactions and the characterization of patients, drugs involved and triggers.

Le cancer est désormais considéré comme une maladie chronique touchant une population toujours croissante. Une prise en charge et un suivi à long terme, à l’origine d’un bouleversement de la vie des patients et de leur entourage, semblent nécessaires et sont susceptibles d’initier une réorganisation du système de santé. Dans ce travail de thèse interdisciplinaire, nous nous sommes intéressés à l’impact du cancer sur le vécu psychologique et psychosocial des patients en France, en choisissant le modèle du cancer de la prostate. Pour cela, nous avons souhaité combiner deux études. L’une portait sur l’état de santé sexuelle des patients atteints d’un cancer de la prostate via une approche quantitative descriptive basée sur les données représentatives des enquêtes nationales VICAN. L’autre visait à déterminer l’impact du cancer de la prostate sur le couple et sa qualité de vie via une approche compréhensive qualitative complémentaire, focalisée sur une prise en charge en Surveillance Active et basée sur des entretiens semi-directifs de patients et de leurs conjointes. L’analyse des données a permis de montrer une détérioration de la santé sexuelle des patients, selon différents déterminants non nécessairement médicaux, et un endommagement du couple et des relations affectives perçues, avec des stratégies d’ajustements divergentes pour chacun des membres du couple, malgré une prise en charge initialement considérée comme optimale et indemne de conséquences. Une approche pluridisciplinaire pourrait permettre un accompagnement complet des couples pour une amélioration de leurs vécus, de leur bien-être et de leur qualité de vie / Cancer is now considered as a chronic disease affecting an ever-increasing population. Long-term care and follow-up, which are responsible of lives disruptions on patients and their relatives, seem necessary and likely to initiate health system reorganization. In this interdisciplinary thesis work, we focused on the impact of cancer on the psychological and psychosocial experiences of patients in France, by choosing the prostate cancer model. To do this, we decided to combine two studies. One aimed on the sexual health status of prostate cancer patients through a descriptive quantitative approach based on data representative of VICAN national surveys. The other one concentrated on the impact of prostate cancer on the couple and its quality of life through a complementary comprehensive qualitative approach, focused on Active Surveillance management and based on semi-directive interviews of patients and their spouses. The data analysis showed deterioration in patients' sexual health associated to several factors, which are not necessarily medical ones, and damages in the couple and perceived affective relationships, with divergent coping strategies for each member of the couple, despite a care management initially considered as optimal and free of consequences. A multidisciplinary approach could help couples to improve their experiences, well-being and quality of life

Die Mehrzahl der jährlich 400.000 bis 600.000 Krankenhausinfektionen in Deutschland wird von Erregern der sog. ESCAPE-Gruppe (Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa und verschiedene Enterobacteriaceae, u.a. Klebsiella pneumoniae) verursacht. Besondere Sorge bereitet dabei die Ausbreitung von K. pneumoniae-Stämmen mit enzymvermittelter Resistenz gegenüber Carbapenem-Antibiotika (K. pneumoniae-Carbapenemase, KPC) und die Zunahme von C. difficile-Infektionen (CDI) durch hypervirulente Epidemiestämme (z.B. Ribotyp 027). Die spezifischen Erfahrungen eines prolongierten Ausbruchsgeschehens durch einen KPC-bildenden K. pneumoniae-Stamm (KPC-KP) am Leipziger Universitätsklinikum machen deutlich, dass bei diesem Erregertyp ein hohes Transmissionspotential bei enormer Tenazität (Umweltresistenz) zu berücksichtigen ist, ein Versagen von Standardhygienemaßnahmen in Betracht zu ziehen ist, und Infektionsketten oftmals unklar bleiben. Die Anwendung von Antibiotika ist bei KPC-KP-Infektionen auf einzelne Substanzen (Colistin, Tigecyclin, Gentamicin) beschränkt und vor allem bei immunsupprimierten Patienten (z.B. Lebertransplantierte) mit einem relevanten Risiko des Therapieversagens behaftet. Die Therapie von CDI wird gerade bei Immunsupprimierten durch eine steigende Zahl an Rezidiven erschwert, die teilweise antibiotisch (Vancomycin, Fidaxomicin) nicht beherrschbar sind, so dass alternative Therapieverfahren wie die fäkale Bakterientherapie („Stuhltransplantation“) zur Anwendung kommen. CDI-Rezidive, aber auch eine dauerhafte intestinale Besiedelung mit multiresistenten Enterobakterien wie KPC-KP, scheinen neben wirtsspezifischen Faktoren der Immunantwort durch eine Dysregulation der physiologischen intestinalen Standortflora mit Störung der Kolonisationsresistenz bedingt zu sein. Der Versuch einer Eradikationsbehandlung von Patienten mit persistierender intestinaler Besiedelung durch KPC-KP mittels oraler Applikation der nicht resorbierbaren Antibiotika Colistin und Gentamicin ist mit einem relevanten Risiko der Entstehung von Sekundärresistenzen behaftet. Die Zulassung neuer, besser wirksamer Antibiotika ist für die nächsten Jahre nicht in Sicht, so dass der Infektionsprävention überragende Bedeutung zukommt. Die Erfahrungen der KPC-Ausbruchsbewältigung am Leipziger Universitätsklinikum zeigen, dass nahezu lückenlose Compliance bei der Händedesinfektion, rigoros praktizierte und kontrollierte Barriere- und Isolationsmaßnahmen, Optimierung des Gebrauchs von Breitspektrum-Antibiotika (sog. „Antibiotic Stewardship“) und systematisches mikrobiologisches Erregerscreening dabei unabdingbar sind. Nachhaltige Verbesserungen hinsichtlich der globalen Ausbreitung von multiresistenten Krankenhausbakterien werden sich nur durch grundlegende Umgestaltungen in Umwelt, Landwirtschaft, Tierzucht und Gesundheitswesen mit sparsamer und möglichst gezielter Anwendung von Antibiotika erzielen lassen. Um Risikopopulationen hospitalisierter Patienten vor potentiell lebensbedrohlichen Erregertransmissionen effektiv schützen zu können, sind erweiterte Surveillance und konsequent umgesetzte krankenhaushygienische Maßnahmen erforderlich.

Introduction: Targeted biopsy of tumour-suspicious lesions detected in multiparametric magnetic resonance imaging (mpMRI) plays an increasing role in the active surveillance (AS) of patients with low-risk prostate cancer (PCa). The aim of this study was to compare MRI/ultrasound-fusion biopsy (fusPbx) with systematic biopsy (sysPbx) in patients undergoing biopsy for AS. Methods: Patients undergoing mpMRI and transperineal fusPbx combined with transrectal sysPbx (comPbx) as surveillance biopsy were investigated. The detection of Gleason score upgrading and reclassification according to Prostate Cancer Research International Active Surveillance criteria were evaluated. Results: Eighty-three patients were enrolled. PCa upgrading was detected in 39% by fusPbx and in 37% by sysPbx (p = 1.0). The percentage of patients who were reclassified in fusPbx and sysPbx (p = 0.45) were 64 and 59% respectively. ComPbx detected more frequently tumour upgrading than fusPbx (71 vs. 64%, p = 0.016) and sysPbx (71 vs. 59%, p < 0.001) and more patients had to be reclassified after comPbx than after fusPbx or sysPbx alone. Conclusions: The combination of fusPbx and sysPbx outperforms both modalities alone with regard to the detection of upgrading and reclassification in patients under AS. Because a high missing rate of significant PCa still exists in both biopsy modalities, a combination of fusPbx and sysPbx should be recommended in these patients.

Die Mehrzahl der jährlich 400.000 bis 600.000 Krankenhausinfektionen in Deutschland wird von Erregern der sog. ESCAPE-Gruppe (Enterococcus faecium, Staphylococcus aureus, Clostridium difficile, Acinetobacter baumannii, Pseudomonas aeruginosa und verschiedene Enterobacteriaceae, u.a. Klebsiella pneumoniae) verursacht. Besondere Sorge bereitet dabei die Ausbreitung von K. pneumoniae-Stämmen mit enzymvermittelter Resistenz gegenüber Carbapenem-Antibiotika (K. pneumoniae-Carbapenemase, KPC) und die Zunahme von C. difficile-Infektionen (CDI) durch hypervirulente Epidemiestämme (z.B. Ribotyp 027). Die spezifischen Erfahrungen eines prolongierten Ausbruchsgeschehens durch einen KPC-bildenden K. pneumoniae-Stamm (KPC-KP) am Leipziger Universitätsklinikum machen deutlich, dass bei diesem Erregertyp ein hohes Transmissionspotential bei enormer Tenazität (Umweltresistenz) zu berücksichtigen ist, ein Versagen von Standardhygienemaßnahmen in Betracht zu ziehen ist, und Infektionsketten oftmals unklar bleiben. Die Anwendung von Antibiotika ist bei KPC-KP-Infektionen auf einzelne Substanzen (Colistin, Tigecyclin, Gentamicin) beschränkt und vor allem bei immunsupprimierten Patienten (z.B. Lebertransplantierte) mit einem relevanten Risiko des Therapieversagens behaftet. Die Therapie von CDI wird gerade bei Immunsupprimierten durch eine steigende Zahl an Rezidiven erschwert, die teilweise antibiotisch (Vancomycin, Fidaxomicin) nicht beherrschbar sind, so dass alternative Therapieverfahren wie die fäkale Bakterientherapie („Stuhltransplantation“) zur Anwendung kommen. CDI-Rezidive, aber auch eine dauerhafte intestinale Besiedelung mit multiresistenten Enterobakterien wie KPC-KP, scheinen neben wirtsspezifischen Faktoren der Immunantwort durch eine Dysregulation der physiologischen intestinalen Standortflora mit Störung der Kolonisationsresistenz bedingt zu sein. Der Versuch einer Eradikationsbehandlung von Patienten mit persistierender intestinaler Besiedelung durch KPC-KP mittels oraler Applikation der nicht resorbierbaren Antibiotika Colistin und Gentamicin ist mit einem relevanten Risiko der Entstehung von Sekundärresistenzen behaftet. Die Zulassung neuer, besser wirksamer Antibiotika ist für die nächsten Jahre nicht in Sicht, so dass der Infektionsprävention überragende Bedeutung zukommt. Die Erfahrungen der KPC-Ausbruchsbewältigung am Leipziger Universitätsklinikum zeigen, dass nahezu lückenlose Compliance bei der Händedesinfektion, rigoros praktizierte und kontrollierte Barriere- und Isolationsmaßnahmen, Optimierung des Gebrauchs von Breitspektrum-Antibiotika (sog. „Antibiotic Stewardship“) und systematisches mikrobiologisches Erregerscreening dabei unabdingbar sind. Nachhaltige Verbesserungen hinsichtlich der globalen Ausbreitung von multiresistenten Krankenhausbakterien werden sich nur durch grundlegende Umgestaltungen in Umwelt, Landwirtschaft, Tierzucht und Gesundheitswesen mit sparsamer und möglichst gezielter Anwendung von Antibiotika erzielen lassen. Um Risikopopulationen hospitalisierter Patienten vor potentiell lebensbedrohlichen Erregertransmissionen effektiv schützen zu können, sind erweiterte Surveillance und konsequent umgesetzte krankenhaushygienische Maßnahmen erforderlich.