Leptospirosis: A dual threat - predisposing risk for renal transplant and trigger for renal transplant dysfunction.

Leptospirosis (LTPS) is a bacterial infection that affects humans, often with mild or no symptoms. It is estimated that approximately 10 % of patients with LTPS may experience multi-organ dysfunction, including renal abnormalities. In regions where LTPS is widespread, a considerable number of instances involving acute kidney injury (AKI) and chronic kidney disease (CKD) of unknown etiology (CKDu) have been reported. Additionally, studies have shown a correlation between kidney graft dysfunction in patients with stable kidney transplants after LTPS. These findings indicate that exposure to LTPS may increase the likelihood of kidney transplantation due to the onset of both acute and chronic kidney injuries. Simultaneously, it poses a potential risk to the stability of kidney grafts. Unfortunately, there is limited scientific literature addressing this issue, making it difficult to determine the negative impact that LTPS may have, such as its role as a risk factor for the need of kidney transplantation or as a threat to individuals who have undergone kidney transplants. This study aims to shed light on the immune mechanisms triggered during LTPS infection and their importance in both kidney damage and allograft dysfunction.

Healthcare-Associated Infections and the Use of Antibiotics in German Hospitals.

BACKGROUND: A national point prevalence survey (PPS) of healthcare-associated infections (HAI) and antibiotic use (AU) was carried out in Germany in 2022 in the framework of the European PPS conducted by the European Centre for Disease Prevention and Control (ECDC). The objective was to determine the prevalence of HAI and AU in German hospitals and to compare the obtained values with those of the most recent previous PPS, which was carried out in 2016. METHODS: The German National Reference Center for the Surveillance of Nosocomial Infections was entrusted with the organization of the PPS of 2022. As recommended by the ECDC, each hospital in a representative sample of 50 hospitals was invited to participate, and all other interested hospitals in Germany were also able to participate if desired. The data were collected by specially trained hospital staff in May, June, and July 2022. The definitions and methods put forth by the ECDC were used. RESULTS: Data from 66 586 patients in 252 hospitals were included. The prevalence of HAI in all participating hospitals was 4.9%, and that of AU was 26.9%. The HAI and AU prevalences were essentially unchanged in comparison to 2016. The most common types of HAI were surgical site infection (23.5%), lower respiratory tract infection (21.6%), and urinary tract infection (19.0%). CONCLUSION: HAI were just as frequent in 2022 as in 2016, affecting approximately one in twenty hospitalized patients on any given day.

Towards interoperability in infection control: a standard data model for microbiology.

The COVID-19 pandemic has made it clear: sharing and exchanging data among research institutions is crucial in order to efficiently respond to global health threats. This can be facilitated by defining health data models based on interoperability standards. In Germany, a national effort is in progress to create common data models using international healthcare IT standards. In this context, collaborative work on a data set module for microbiology is of particular importance as the WHO has declared antimicrobial resistance one of the top global public health threats that humanity is facing. In this article, we describe how we developed a common model for microbiology data in an interdisciplinary collaborative effort and how we make use of the standard HL7 FHIR and terminologies such as SNOMED CT or LOINC to ensure syntactic and semantic interoperability. The use of international healthcare standards qualifies our data model to be adopted beyond the environment where it was first developed and used at an international level.

Risk factors for nosocomial SARS-CoV-2 infections in patients: results from a retrospective matched case-control study in a tertiary care university center.

BACKGROUND: Factors contributing to the spread of SARS-CoV-2 outside the acute care hospital setting have been described in detail. However, data concerning risk factors for nosocomial SARS-CoV-2 infections in hospitalized patients remain scarce. To close this research gap and inform targeted measures for the prevention of nosocomial SARS-CoV-2 infections, we analyzed nosocomial SARS-CoV-2 cases in our hospital during a defined time period. METHODS: Data on nosocomial SARS-CoV-2 infections in hospitalized patients that occurred between May 2020 and January 2021 at Charité university hospital in Berlin, Germany, were retrospectively gathered. A SARS-CoV-2 infection was considered nosocomial if the patient was admitted with a negative SARS-CoV-2 reverse transcription polymerase chain reaction test and subsequently tested positive on day five or later. As the incubation period of SARS-CoV-2 can be longer than five days, we defined a subgroup of "definite" nosocomial SARS-CoV-2 cases, with a negative test on admission and a positive test after day 10, for which we conducted a matched case-control study with a one to one ratio of cases and controls. We employed a multivariable logistic regression model to identify factors significantly increasing the likelihood of nosocomial SARS-CoV-2 infections. RESULTS: A total of 170 patients with a nosocomial SARS-CoV-2 infection were identified. The majority of nosocomial SARS-CoV-2 patients (n = 157, 92%) had been treated at wards that reported an outbreak of nosocomial SARS-CoV-2 cases during their stay or up to 14 days later. For 76 patients with definite nosocomial SARS-CoV-2 infections, controls for the case-control study were matched. For this subgroup, the multivariable logistic regression analysis revealed documented contact to SARS-CoV-2 cases (odds ratio: 23.4 (95% confidence interval: 4.6-117.7)) and presence at a ward that experienced a SARS-CoV-2 outbreak (odds ratio: 15.9 (95% confidence interval: 2.5-100.8)) to be the principal risk factors for nosocomial SARS-CoV-2 infection. CONCLUSIONS: With known contact to SARS-CoV-2 cases and outbreak association revealed as the primary risk factors, our findings confirm known causes of SARS-CoV-2 infections and demonstrate that these also apply to the acute care hospital setting. This underscores the importance of rapidly identifying exposed patients and taking adequate preventive measures.

Implementation of an automated cluster alert system into the routine work of infection control and hospital epidemiology: experiences from a tertiary care university hospital.

BACKGROUND: Early detection of clusters of pathogens is crucial for infection prevention and control (IPC) in hospitals. Conventional manual cluster detection is usually restricted to certain areas of the hospital and multidrug resistant organisms. Automation can increase the comprehensiveness of cluster surveillance without depleting human resources. We aimed to describe the application of an automated cluster alert system (CLAR) in the routine IPC work in a hospital. Additionally, we aimed to provide information on the clusters detected and their properties. METHODS: CLAR was continuously utilized during the year 2019 at Charité university hospital. CLAR analyzed microbiological and patient-related data to calculate a pathogen-baseline for every ward. Daily, this baseline was compared to data of the previous 14 days. If the baseline was exceeded, a cluster alert was generated and sent to the IPC team. From July 2019 onwards, alerts were systematically categorized as relevant or non-relevant at the discretion of the IPC physician in charge. RESULTS: In one year, CLAR detected 1,714 clusters. The median number of isolates per cluster was two. The most common cluster pathogens were Enterococcus faecium (n = 326, 19 %), Escherichia coli (n = 274, 16 %) and Enterococcus faecalis (n = 250, 15 %). The majority of clusters (n = 1,360, 79 %) comprised of susceptible organisms. For 906 alerts relevance assessment was performed, with 317 (35 %) alerts being classified as relevant. CONCLUSIONS: CLAR demonstrated the capability of detecting small clusters and clusters of susceptible organisms. Future improvements must aim to reduce the number of non-relevant alerts without impeding detection of relevant clusters. Digital solutions to IPC represent a considerable potential for improved patient care. Systems such as CLAR could be adapted to other hospitals and healthcare settings, and thereby serve as a means to fulfill these potentials.

Papel de los tejidos orales durante la infección por SARS-CoV-2 / Role of oral tissues in SARS-CoV-2 infection

La actual pandemia de COVID-19 provocada por el virus SARS-CoV-2 es un problema de salud que afecta a la población globalmente. Su desarrollo puede ser asintomático o exhibir manifestaciones clínicas moderadas o severas dependiendo en gran medida de la respuesta inmune de quien la padece. Esta enfermedad afecta principalmente a los pulmones a través del desarrollo del síndrome respiratorio agudo severo (SRAS), tanto como por la «tormenta de citocinas¼, una respuesta inflamatoria exacerbada que podría provocar una falla multisistémica y, en casos severos, la muerte. Se conoce que la enzima convertidora de angiotensina 2 (ECA-2), presente en diversos tejidos del cuerpo, actúa como receptor funcional del virus SARS-CoV-2 facilitando la entrada de éste a las células. Se ha demostrado la presencia de dicho receptor en varios tejidos orales, por lo que se puede considerar a la cavidad bucal como una vía latente de infección por dicho coronavirus, ya que su mecanismo de transmisión es a través de la inhalación de partículas virales, ya sea por vía nasal u oral. Así mismo, la presencia de carga vírica en la saliva y algunos de los síntomas de la COVID-19, por ejemplo la ageusia, pueden indicar la presencia de contagio viral en etapas tempranas. La presente revisión muestra evidencia que sugiere que diversos tejidos en la cavidad oral podrían ser considerados sitios potenciales de contagio por el SARS-CoV-2, teniendo un papel importante en el mecanismo de transmisión y en el desarrollo de coinfecciones (AU)

The COVID-19 pandemic caused by the SARS-CoV-2 virus is currently a global healthcare problem. The onset of this disease can exhibit several clinical manifestations ranging from mild to severe symptoms, depending on the individual's immune response. COVID-19 primarily affects the lungs by developing the Severe Acute Respiratory Syndrome (SARS) and the «cytokine storm¼, an exacerbated inflammatory reaction that can lead to multiorgan failure and consequently death. The angiotensin-converting enzyme 2 (ACE-2), present in several tissues in the human body, is known to act as the functional receptor of the SARS-CoV-2 germ facilitating its entrance into the cells. Such receptor is also present in diverse oral cavity tissues, indicating a latent route of infection due to its influence in the transmission mechanism by inhalation, either oral or nasal, of virus particles. Also, viral load in saliva and taste disorder symptoms like ageusia could indicate a viral infection in its early stages. This article presents evidence suggesting that several tissues in the oral cavity can be considered potential sites of SARS-CoV-2 infection, thus playing an essential role in the transmission mechanism and development of co-infections (AU)

Self-Assembling Peptides as an Emerging Platform for the Treatment of Metabolic Syndrome.

Metabolic syndrome comprises a cluster of comorbidities that represent a major risk of developing chronic diseases, such as type II diabetes, cardiovascular diseases, and stroke. Alarmingly, metabolic syndrome reaches epidemic proportions worldwide. Today, lifestyle changes and multiple drug-based therapies represent the gold standard to address metabolic syndrome. However, such approaches face two major limitations: complicated drug therapeutic regimes, which in most cases could lead to patient incompliance, and limited drug efficacy. This has encouraged scientists to search for novel routes to deal with metabolic syndrome and related diseases. Within such approaches, self-assembled peptide formulations have emerged as a promising alternative for treating metabolic syndrome. In particular, self-assembled peptide hydrogels, either as acellular or cell-load three-dimensional scaffoldings have reached significant relevance in the biomedical field to prevent and restore euglycemia, as well as for controlling cardiovascular diseases and obesity. This has been possible thanks to the physicochemical tunability of peptides, which are developed from a chemical toolbox of versatile amino acids enabling flexibility of designing a wide range of self-assembled/co-assembled nanostructures forming biocompatible viscoelastic hydrogels. Peptide hydrogels can be combined with several biological entities, such as extracellular matrix proteins, drugs or cells, forming functional biologics with therapeutic ability for treatment of metabolic syndrome-comorbidities. Additionally, self-assembly peptides combine safety, tolerability, and effectivity attributes; by this presenting a promising platform for the development of novel pharmaceuticals capable of addressing unmet therapeutic needs for diabetes, cardiovascular disorders and obesity. In this review, recent advances in developing self-assembly peptide nanostructures tailored for improving treatment of metabolic syndrome and related diseases will be discussed from basic research to preclinical research studies. Challenges facing the development of approved medicinal products based on self-assembling peptide nanomaterials will be discussed in light of regulatory requirement for clinical authorization.

Lean back and wait for the alarm? Testing an automated alarm system for nosocomial outbreaks to provide support for infection control professionals.

INTRODUCTION: Outbreaks of communicable diseases in hospitals need to be quickly detected in order to enable immediate control. The increasing digitalization of hospital data processing offers potential solutions for automated outbreak detection systems (AODS). Our goal was to assess a newly developed AODS. METHODS: Our AODS was based on the diagnostic results of routine clinical microbiological examinations. The system prospectively counted detections per bacterial pathogen over time for the years 2016 and 2017. The baseline data covers data from 2013-2015. The comparative analysis was based on six different mathematical algorithms (normal/Poisson and score prediction intervals, the early aberration reporting system, negative binomial CUSUMs, and the Farrington algorithm). The clusters automatically detected were then compared with the results of our manual outbreak detection system. RESULTS: During the analysis period, 14 different hospital outbreaks were detected as a result of conventional manual outbreak detection. Based on the pathogens' overall incidence, outbreaks were divided into two categories: outbreaks with rarely detected pathogens (sporadic) and outbreaks with often detected pathogens (endemic). For outbreaks with sporadic pathogens, the detection rate of our AODS ranged from 83% to 100%. Every algorithm detected 6 of 7 outbreaks with a sporadic pathogen. The AODS identified outbreaks with an endemic pathogen were at a detection rate of 33% to 100%. For endemic pathogens, the results varied based on the epidemiological characteristics of each outbreak and pathogen. CONCLUSION: AODS for hospitals based on routine microbiological data is feasible and can provide relevant benefits for infection control teams. It offers in-time automated notification of suspected pathogen clusters especially for sporadically occurring pathogens. However, outbreaks of endemically detected pathogens need further individual pathogen-specific and setting-specific adjustments.

The quality of antimicrobial prescribing in acute care hospitals: results derived from a national point prevalence survey, Germany, 2016.

BackgroundRobust data on the quality of antimicrobial prescriptions in German acute care hospitals are scarce. To establish and implement antimicrobial stewardship (AMS) measures and to increase prudent antimicrobial use (AMU), the identification of appropriate process and quality indicators is pertinent.AimOur main objective was to identify parameters associated with adequate AMU and inadequate AMU by analysing point prevalence data. Our secondary goal was to describe the current state of AMS implementation in Germany.MethodsA national point prevalence survey for healthcare-associated infections and AMU was conducted in German hospitals in 2016. Data on structure and process parameters were also collected. Recorded antimicrobial prescriptions were divided into adequate, inadequate and undefinable AMU. A multivariable linear regression analysis was performed to examine the correlation of selected structure and process parameters with the adequacy of recorded antimicrobials.ResultsData from 218 acute care hospitals, 64,412 patients and 22,086 administered antimicrobials were included. Multivariable linear regression analysis revealed that documentation of a reason for AMU in the patient notes increased the likelihood of adequate AMU and decreased the likelihood of inadequate AMU significantly (p < 0.001), while tertiary care hospital type had the opposite effect (p < 0.001).ConclusionThrough associating structural and process parameters with adequacy of AMU, we identified parameters that increased the odds of prudent AMU. Documentation was a key element for improving AMU. Revealed deficits regarding the implementation of AMS in German hospitals concerning dedicated staff for AMS activities and establishment of regular AMU training and AMU audits should be tackled.

Antibiotic consumption in Germany: first data of a newly implemented web-based tool for local and national surveillance.

Objectives: The features of a newly established, web-based surveillance system for hospital antibiotic consumption are described and data on broad-spectrum antibiotic use in German acute care hospitals are presented. Methods: The watch- and reserve-group antibiotics, two categories of antibiotics derived from the WHO Essential Medicines List comprising key agents for antimicrobial stewardship, were used as a framework for data analysis. The median antibiotic consumption densities (ACDs; DDD/100 patient days) for the years 2015/16 based on data from 137 acute care hospitals have been calculated for whole facilities, ICUs and medical and surgical departments, stratified by type of care. Results: The new web-based system provides real-time surveillance at unit and facility levels, accessible to all relevant stakeholders. User-defined reports are available via an interactive database, various report types support different approaches to analysis, and different complementing quantification measures of antimicrobial consumption are available. Watch- and reserve-group antibiotics accounted for 42% and 2% of total antibiotic use, respectively. Surgical services presented with considerably lower median ACDs of the watch-group antibiotics compared with medical services. Tertiary care hospitals exhibited higher ACDs of the reserve-group antibiotics and carbapenems than primary/secondary care hospitals, while the ACDs of the watch-group antibiotics as a whole did not differ significantly. Comparing the proportional use with other European countries revealed a relatively high use of the watch-group, ranking beyond the 75th percentile. Conclusions: Because of its particular features the new web-based surveillance system is a valuable tool for antimicrobial stewardship. The WHO categories of watch- and reserve-group antibiotics proved to be a useful framework for the analysis of hospital antibiotic consumption data.

Evaluation of the immunogenic capability of the BCG strains BCGΔBCG1419c and BCGΔBCG1416c in a three-dimensional human lung tissue model.

Tuberculosis (TB) still remains as an unmet global threat. The current vaccine is not fully effective and novel alternatives are needed. Here, two vaccine candidate strains derived from BCG carrying deletions in the BCG1416c or BCG1419c genes were analysed for their capacity to modulate the cytokine/chemokine profile and granuloma formation in a human lung tissue model (LTM). We show that the clustering of monocytes, reminiscent of early granuloma formation, in LTMs infected with BCG strains was similar for all of them. However, BCGΔBCG1419c, like M. tuberculosis, was capable of inducing the production of IL-6 in contrast to the other BCG strains. This work suggests that LTM could be a useful ex vivo assay to evaluate the potential immunogenicity of novel TB vaccine candidates.

Antimicrobial usage in German acute care hospitals: results of the third national point prevalence survey and comparison with previous national point prevalence surveys.

Objectives: Previous point prevalence surveys (PPSs) revealed the potential for improving antimicrobial usage (AU) in German acute care hospitals. Data from the 2016 German national PPS on healthcare-associated infections and AU were used to evaluate efforts in antimicrobial stewardship (AMS). Methods: A national PPS in Germany was organized by the German National Reference Centre for Surveillance of Nosocomial Infections in 2016 as part of the European PPS initiated by the ECDC. The data were collected in May and June 2016. Results were compared with data from the PPS 2011. Results: A total of 218 hospitals with 64 412 observed patients participated in the PPS 2016. The prevalence of patients with AU was 25.9% (95% CI 25.6%-26.3%). No significant increase or decrease in AU prevalence was revealed in the group of all participating hospitals. Prolonged surgical prophylaxis was found to be common (56.1% of all surgical prophylaxes on the prevalence day), but significantly less prevalent than in 2011 (P < 0.01). The most frequently administered antimicrobial groups were penicillins plus ß-lactamase inhibitors (BLIs) (23.2%), second-generation cephalosporins (12.9%) and fluoroquinolones (11.3%). Significantly more penicillins plus BLIs and fewer second-generation cephalosporins and fluoroquinolones were used in 2016. Overall, an increase in the consumption of broad-spectrum antimicrobials was noted. For 68.7% of all administered antimicrobials, the indication was documented in the patient notes. Conclusions: The current data reaffirm the points of improvement that previous data identified and reveal that recent efforts in AMS in German hospitals require further intensification.

A Randomized, Double-Blind, Placebo-Controlled Phase II Study of the Efficacy and Safety of Monotherapy Ontuxizumab (MORAb-004) Plus Best Supportive Care in Patients with Chemorefractory Metastatic Colorectal Cancer.

Purpose: The purpose of this study was to evaluate the safety and efficacy of ontuxizumab (MORAb-004), a monoclonal antibody that interferes with endosialin (tumor endothelial marker-1) function, in patients with chemorefractory metastatic colorectal cancer and to identify a responsive patient population based on biomarkers.Experimental Design: This was a randomized, double-blind, placebo-controlled, phase II study. Patients were randomly assigned in a 2:1 ratio to receive weekly intravenous ontuxizumab (8 mg/kg) or placebo plus best supportive care until progression or unacceptable toxicity. Tissue and blood biomarkers were evaluated for their ability to identify a patient population that was responsive to ontuxizumab.Results: A total of 126 patients were enrolled. No significant difference between the ontuxizumab and placebo groups was evident for the primary endpoint of progression-free survival (PFS), with a median PFS of 8.1 weeks in each group (HR, 1.13; 95% confidence interval, 0.76-1.67; P = 0.53). There were no significant differences between groups for overall survival (OS) or overall response rate (ORR). The most common treatment-emergent adverse events (TEAEs) in the ontuxizumab group (vs. the placebo group, respectively) were fatigue (53.7% vs. 47.5%), nausea (39.0% vs. 35.0%), decreased appetite (34.1% vs. 27.5%), and constipation (28.0% vs. 32.5%). The most common grade 3/4 TEAE in the ontuxizumab group versus placebo was back pain (11.0% vs. 0%). No single biomarker clearly identified patients responsive to ontuxizumab.Conclusions: No benefit with ontuxizumab monotherapy compared with placebo for clinical response parameters of PFS, OS, or ORR was demonstrated. Ontuxizumab was well tolerated. Clin Cancer Res; 24(2); 316-25. ©2017 AACR.

The Prevalence of Nosocomial Infection and Antibiotic Use in German Hospitals.

BACKGROUND: In 2011 and again in 2016, the European Centre for Disease Prevention and Control (ECDC) asked all European countries to carry out nationwide studies on the prevalence of nosocomial infection (NI) and antibiotic use (AU). Data on NI and AU constitute an essential basis for the development of measures to prevent infection and lessen antibiotic resistance. METHODS: The German prevalence study of 2016 was carried out according to the ECDC protocol. Alongside a sample of 49 acute-care hospitals requested by the ECDC that was representative in terms of size (number of beds), further hospitals were invited to participate as well. Analyses were made of the overall group (218 hospitals, 64 412 patients), the representative group (49 hospitals), and the core group (46 hospitals). The core group consisted of the hospitals that had participated in the study of 2011. RESULTS: The prevalence of patients with NI was 4.6% in the overall group in 2016; it had been 5.1% in 2011 (p <0.01). In the representative group, the prevalence was 3.6% (compared to 5.1% in 2011, p <0.01). In the core group, the prevalence of NI was the same in 2016 as it had been in 2011. The prevalence of patients with ABU in the overall group remained the same, but a fall was seen in the representative group (21.5% versus 23.3%; p <0.01) and a rise in the core group (27.3% versus 26.2%; p = 0.02). The staff-patient ratio among the infection prevention and control professionals improved in all three groups. CONCLUSION: A decrease in NI and AU prevalence was seen in the representative group, while mixed results were seen in the other analyzed groups. Further efforts to reduce NI and ABA are clearly necessary.

Declaración ante los resultados del ensayo clínico Symplicity HTN 3. Grupo de estudio de la hipertensión arterial resistente / Position paper on the results of Symplicity HTN-3 trial. Grupo de estudio de la hipertensión arterial resistente

La denervación de las arterias renales ha sido una alternativa para el tratamiento de la hipertensión arterial resistente. Los estudios Symplicity HTN 1 y 2 mostraron en grupos pequeños y no controlados disminuciones de la presión sistólica hasta de 30 mm Hg. Este entusiasmo ha sido opacado por el estudio Symplicity HTN 3, ensayo clínico aleatorizado y controlado con un procedimiento placebo. Sorprendentemente, los resultados sugirieron que la denervación renal tuvo un efecto similar al del placebo, aunque en el análisis de subgrupos preespecificados los pacientes que no eran de raza negra, los menores de 65 años y los que tenían función renal normal tuvieron una reducción de la presión arterial sistólica estadísticamente significativa. Esta es una evaluación crítica de los resultados del Symplicity HTN 3 y propone posibles explicaciones para estos. Además, declara la postura de nuestro grupo y las acciones futuras.

Renal artery denervation has shown to be an effective treatment for resistant hypertension. Symplicity HTN 1 and 2 trials showed in small and uncontrolled groups, significant systolic blood pressure reductions down to 30 mm Hg. Symplicity HTN-3, a double blind, randomized, placebo controlled clinical trial shaded this initial enthusiasm. Surprisingly, their results showed that renal denervation has a similar effect to placebo. Pre-specified subgroup analysis showed that non-black race individuals, younger than 65 years and with normal renal function, had a statistically significant systolic blood pressure decrease. This manuscript critically appraises the Symplicity HTN-3 trial, proposing possible explanations for the results. Also declares our group position and future actions regarding renal denervation.

[Position paper on the results of Symplicity HTN-3 trial. Grupo de estudio de la hipertensión arterial resistente]. / Declaración ante los resultados del ensayo clínico Symplicity HTN 3. Grupo de estudio de la hipertensión arterial resistente.

Renal artery denervation has shown to be an effective treatment for resistant hypertension. Symplicity HTN 1 and 2 trials showed in small and uncontrolled groups, significant systolic blood pressure reductions down to 30 mm Hg. Symplicity HTN-3, a double blind, randomized, placebo controlled clinical trial shaded this initial enthusiasm. Surprisingly, their results showed that renal denervation has a similar effect to placebo. Pre-specified subgroup analysis showed that non-black race individuals, younger than 65 years and with normal renal function, had a statistically significant systolic blood pressure decrease. This manuscript critically appraises the Symplicity HTN-3 trial, proposing possible explanations for the results. Also declares our group position and future actions regarding renal denervation.

Nosocomial infection and antibiotic use: a second national prevalence study in Germany.

BACKGROUND: In 2011, seventeen years after the first national study on the prevalence of nosocomial infections and antibiotic use in German hospitals, a second national prevalence study was carried out according to the specifications of the European Centre for Disease Prevention and Control (ECDC). METHODS: The ECDC protocol, containing uniform surveillance definitions and ascertainment methods, was implemented. The only infections counted were those that were active or under treatment with antibiotics on the day of the study. In addition to the representative sample required by the ECDC, which consisted of 46 hospitals, further hospitals participated on a voluntary basis. RESULTS: Data on 41 539 patients in 132 hospitals were analyzed. The prevalence of infections that had arisen during the current hospital stay was 3.8% in the overall group and 3.4% in the representative sample of 9626 patients in 46 hospitals. The prevalence of all nosocomial infections, including those acquired before the current hospital stay and still present upon admission, was 5.1% in both the overall group and the representative sample. The prevalence of antibiotic use on the day of the study was 25.5% and 23.3% in the two groups, respectively. CONCLUSION: The prevalence of nosocomial infection has not changed since 1994, but the prevalence of antibiotic use has increased. In interpreting these findings, one should bear in mind that confounders may have influenced them in different directions: The mean length of hospital stay is now shorter than in 1994, but the mean age of hospitalized patients is higher.

Neuroendocrine liver metastasis treated by using intraarterial therapy: volumetric functional imaging biomarkers of early tumor response and survival.

PURPOSE: To determine if volumetric changes of diffusion-weighted and contrast material-enhanced magnetic resonance (MR) imaging can help assess early tumor response to intraarterial therapy (IAT) in neuroendocrine liver metastasis (NELM). MATERIALS AND METHODS: This retrospective single-center comprehensive imaging analysis was performed in compliance with HIPAA and was institutional review board approved. Informed patient consent was waived. Seventy-one patients (39 men; mean age, 62.3 years) with NELM treated with IAT were analyzed retrospectively. MR studies were performed before and 3-4 weeks after therapy. The index lesion was segmented to provide volumetric functional analysis of apparent diffusion coefficient (ADC) and contrast-enhanced MR imaging in the hepatic arterial phase (HAP) and portal venous phase (PVP). Tumor response was defined as increase in volumetric ADC of 15% or greater and decrease in volumetric enhancement of 25% or greater during the HAP or of 50% or greater during the PVP. Patient overall survival was the primary end point after therapy initiation. Univariate analysis included Kaplan-Meier survival curves. The Cox proportional hazards regression model was used to detect interactions between volumetric ADC and contrast-enhanced MR imaging and to calculate the hazard ratio. RESULTS: There was significant increase in mean volumetric ADC (27%, P < .0001) and significant decrease in mean volumetric enhancement during the HAP (-25.3%, P < .0001) and the PVP (-22.4%, P < .0001) in all patients. Patients who had 15% or greater volumetric ADC increase (n = 49) after therapy had better prognosis than those who had less than 15% increase in volumetric ADC (n = 22) (log-rank test, P < .002). Patients who had 25% or greater decrease in volumetric arterial enhancement (n = 40) or 50% or greater decrease in venous enhancement (n = 18) had better prognosis than those who had less than 25% decrease in volumetric arterial enhancement (n = 31) or less than 50% decrease in venous enhancement (n = 53) (log-rank test, P < .02). CONCLUSION: Volumetric functional MR imaging criteria may act as biomarkers of early response, indicating that these criteria may be important to incorporate in future NELM clinical trials.