Deep learning-assisted radiomics facilitates multimodal prognostication for personalized treatment strategies in low-grade glioma.

Determining the optimal course of treatment for low grade glioma (LGG) patients is challenging and frequently reliant on subjective judgment and limited scientific evidence. Our objective was to develop a comprehensive deep learning assisted radiomics model for assessing not only overall survival in LGG, but also the likelihood of future malignancy and glioma growth velocity. Thus, we retrospectively included 349 LGG patients to develop a prediction model using clinical, anatomical, and preoperative MRI data. Before performing radiomics analysis, a U2-model for glioma segmentation was utilized to prevent bias, yielding a mean whole tumor Dice score of 0.837. Overall survival and time to malignancy were estimated using Cox proportional hazard models. In a postoperative model, we derived a C-index of 0.82 (CI 0.79-0.86) for the training cohort over 10 years and 0.74 (Cl 0.64-0.84) for the test cohort. Preoperative models showed a C-index of 0.77 (Cl 0.73-0.82) for training and 0.67 (Cl 0.57-0.80) test sets. Our findings suggest that we can reliably predict the survival of a heterogeneous population of glioma patients in both preoperative and postoperative scenarios. Further, we demonstrate the utility of radiomics in predicting biological tumor activity, such as the time to malignancy and the LGG growth rate.

A machine learning approach for the factorization of psychometric data with application to the Delis Kaplan Executive Function System.

While a replicability crisis has shaken psychological sciences, the replicability of multivariate approaches for psychometric data factorization has received little attention. In particular, Exploratory Factor Analysis (EFA) is frequently promoted as the gold standard in psychological sciences. However, the application of EFA to executive functioning, a core concept in psychology and cognitive neuroscience, has led to divergent conceptual models. This heterogeneity severely limits the generalizability and replicability of findings. To tackle this issue, in this study, we propose to capitalize on a machine learning approach, OPNMF (Orthonormal Projective Non-Negative Factorization), and leverage internal cross-validation to promote generalizability to an independent dataset. We examined its application on the scores of 334 adults at the Delis-Kaplan Executive Function System (D-KEFS), while comparing to standard EFA and Principal Component Analysis (PCA). We further evaluated the replicability of the derived factorization across specific gender and age subsamples. Overall, OPNMF and PCA both converge towards a two-factor model as the best data-fit model. The derived factorization suggests a division between low-level and high-level executive functioning measures, a model further supported in subsamples. In contrast, EFA, highlighted a five-factor model which reflects the segregation of the D-KEFS battery into its main tasks while still clustering higher-level tasks together. However, this model was poorly supported in the subsamples. Thus, the parsimonious two-factors model revealed by OPNMF encompasses the more complex factorization yielded by EFA while enjoying higher generalizability. Hence, OPNMF provides a conceptually meaningful, technically robust, and generalizable factorization for psychometric tools.

Clonal evolution in diffuse large B-cell lymphoma with central nervous system recurrence.

BACKGROUND: The prognosis of patients with secondary central nervous system lymphoma (SCNSL) is poor and despite massive advances in understanding the mutational landscape of primary diffuse large B-cell lymphoma (DLBCL), the genetic comparison to SCNSL is still lacking. We therefore collected paired samples from six patients with DLBCL with available biopsies from a lymph node (LN) at primary diagnosis and the central nervous system (CNS) at recurrence. PATIENTS AND METHODS: A targeted, massively parallel sequencing approach was used to analyze 216 genes recurrently mutated in DLBCL. Healthy tissue from each patient was also sequenced in order to exclude germline mutations. The results of the primary biopsies were compared with those of the CNS recurrences to depict the genetic background of SCNSL and evaluate clonal evolution. RESULTS: Sequencing was successful in five patients, all of whom had at least one discordant mutation that was not detected in one of their samples. Four patients had mutations that were found in the CNS but not in the primary LN. Discordant mutations were found in genes known to be important in lymphoma biology such as MYC, CARD11, EP300 and CCND3. Two patients had a Jaccard similarity coefficient below 0.5 indicating substantial genetic differences between the primary LN and the CNS recurrence. CONCLUSIONS: This analysis gives an insight into the genetic landscape of SCNSL and confirms the results of our previous study on patients with systemic recurrence of DLBCL with evidence of substantial clonal diversification at relapse in some patients, which might be one of the mechanisms of treatment resistance.

Cefazolin versus anti-staphylococcal penicillins for the treatment of patients with Staphylococcus aureus bacteraemia.

BACKGROUND: For patients with bacteraemia caused by methicillin-sensitive Staphylococcus aureus anti-staphylococcal penicillins (ASPs) or cefazolin are agents of choice. While ASPs are potentially nephrotoxic, cefazolin may be less effective in some S. aureus strains due to an inoculum effect. OBJECTIVES: To perform a systematic literature review and meta-analysis assessing current evidence comparing cefazolin with ASPs for patients with S. aureus bacteraemia (SAB). METHODS: We searched MEDLINE, ISI Web of Science (Science Citation Index Expanded) and the Cochrane Database as well as clinicaltrials.gov from inception to 26 June 2018. All studies investigating the effects of cefazolin versus ASP in patients with methicillin-sensitive SAB were eligible for inclusion regardless of study design, publication status or language. Additional information was requested by direct author contact. A meta-analysis to estimate relative risks (RRs) with the corresponding 95% confidence intervals (CIs) was performed. Statistical heterogeneity was estimated using I2. The primary endpoint was 90-day all-cause mortality. The Newcastle-Ottawa Scale (NOS) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used for study and data quality assessment. RESULTS: Fourteen non-randomized studies were included. Seven reported the primary endpoint (RR 0.71 (0.50, 1.02), low quality of evidence). Cefazolin treatment may be associated with lower 30-day mortality rates (RR 0.70 (0.54, 0.91), low quality of evidence) and less nephrotoxicity (RR 0.36 (0.21, 0.59), (low quality of evidence)). We are uncertain whether cefazolin and ASP differ regarding treatment failure/relapse as the quality of the evidence has been assessed as very low (RR of 0.84 (0.59, 1.18)). For patients with endocarditis (RR 0.71 (0.12, 4.05)) or abscesses (RR 1.17 (0.30, 4.63)), cefazolin treatment may be associated with equal 30-day and 90-day mortality (low quality of evidence). CONCLUSIONS: Cefazolin seemed to be at least equally as effective as ASPs while being associated with less nephrotoxicity.

MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis.

BACKGROUND: Currently, no suitable clinical marker for detection of septic immunosuppression is available. We aimed at identifying microRNAs that could serve as biomarkers of T-cell mediated immunoparalysis in sepsis. METHODS: RNA was isolated from purified T-cells or from whole blood cells obtained from septic patients and healthy volunteers. Differentially regulated miRNAs were identified by miRNA Microarray (n = 7). Validation was performed via qPCR (n = 31). RESULTS: T-cells of septic patients revealed characteristics of immunosuppression: Pro-inflammatory miR-150 and miR-342 were downregulated, whereas anti-inflammatory miR-15a, miR-16, miR-93, miR-143, miR-223 and miR-424 were upregulated. Assessment of T-cell effector status showed significantly reduced mRNA-levels of IL2, IL7R and ICOS, and increased levels of IL4, IL10 and TGF-ß. The individual extent of immunosuppression differed markedly. MicroRNA-143, - 150 and - 223 independently indicated T-cell immunoparalysis and significantly correlated with patient's IL7R-/ICOS-expression and SOFA-scores. In whole blood, composed of innate and adaptive immune cells, both traits of immunosuppression and hyperinflammation were detected. Importantly, miR-143 and miR-150 - both predominantly expressed in T-cells - retained strong power of discrimination also in whole blood samples. CONCLUSIONS: These findings suggest miR-143 and miR-150 as promising markers for detection of T-cell immunosuppression in whole blood and may help to develop new approaches for miRNA-based diagnostic in sepsis.

Dual antiretroviral therapy with tenofovir (TDF) and darunavir/ritonavir (DRV/RTV) in an HIV-1 positive patient: a case report, review, and meta-analysis of the literature on dual treatment strategies using protease inhibitors in combination with an NRTI.

BACKGROUND: Here, we report the case of an HIV positive patient under a dual antiretroviral drug regimen with tenofovir disoproxil and darunavir/ritonavir with stable clinical, virological, and immunological response over 126 weeks. Dual antiretroviral therapy has the advantage of reduced toxicity and lower health care costs, treatment failure and fostering drug resistance are perceived risks. Optimal drug combinations and indication criteria for dual treatment remain controversial. Nevertheless, first clinical trials indicate non-inferiority for combinations of nucleoside reverse transcriptase inhibitors and protease inhibitors. This case presents the combination of tenofovir disoproxil in combination with a protease inhibitor as a new potential dual treatment regimen. METHOD: We performed a systematic literature search and meta-analysis of trials comparing dual to triple ART. RESULTS: Literature review revealed nine studies in which dual therapy with a protease inhibitor and an NRTI was compared to triple therapy. We performed a meta-analysis of six trials that reported a 48-week follow-up. In treatment-naïve patients as well when ART switch was assessed, there was no difference in the treatment success in patients with dual ART versus triple. CONCLUSION: We conclude that dual therapy with a protease inhibitor and NRTI is safe and effective. The use of tenofovir in dual treatment as described in our case needs to be assessed in future clinical trials.

CXCL13 as a diagnostic marker of neuroborreliosis and other neuroinflammatory disorders in an unselected group of patients.

BACKGROUND: The C-X-C motif chemokine ligand 13 (CXCL13) and its receptor CXCR5 play an important role in the homing of B-lymphocytes. As a biomarker in the cerebrospinal fluid (CSF), CXCL13 has increasingly been used for the diagnosis of neuroborreliosis (NB). We evaluated the diagnostic and prognostic potential of CXCL13 for NB and other neuroinflammatory diseases in an unselected cohort, paying attention to those patients particularly who might benefit from newly emerging CXCL13-directed therapies. METHODS: We report the CSF CXCL13 concentrations and other relevant baseline characteristics for an unselected cohort of 459 patients. We compare different diagnostic groups and analyse the sensitivity and specificity of CSF CXCL13 as a marker of NB. The course of the CXCL13 concentrations is reported in a subgroup of 19 patients. RESULTS: We confirm the high diagnostic yield of CXCL13 for NB in this unselected cohort. The optimal cut-off for the reliable diagnosis of NB was 93.83 pg/ml, resulting in a sensitivity and specificity of 95 and 97%, respectively (positive predictive value 55.9%, negative predictive value 99.8%), surpassing the sensitivity of both serological testing and PCR. CSF CXCL13 concentration showed a swift response to therapy. Non-NB patients with high CSF CXCL13 concentrations suffered from meningeosis neoplastica or infectious encephalitis. CONCLUSIONS: CXCL13 is a valuable tool for the diagnosis and assessment of therapeutic response in NB. Furthermore, our data point towards an emerging role of CXCL13 in the diagnosis and prognosis of viral encephalitis and meningeosis neoplastica. These results are of particular interest in the light of recently developed approaches to CXCL13-directed therapeutic interventions.

[Antibiotic stewardship and Staphylococcus aureus Bacteremia]. / Antibiotic Stewardship am Beispiel der Staphylococcus aureus Bakteriämie.

Rates of antibiotic resistance are increasing worldwide and impact on the treatment of patients with bacterial infections. A broad and uncritical application in inpatient and outpatient settings as well as in agriculture has been recognized as the main driving force. Antibiotic stewardship (ABS) programs aim at countering this worrisome development using various direct interventions such as infectious disease counseling. Blood stream infections caused by Staphylococcus (S.) aureus are severe infections associated with high mortality rates. ABS interventions such as de-eskalation of the antibiotic regimen or application of narrow-spectrum beta-lactam antibiotics can significantly reduce mortality rates. In this review, we discuss the importance of ABS programs and infectious disease counseling for the treatment of S. aureus blood stream infection.

Study on the utility of a statewide counselling programme for improving mortality outcomes of patients with Staphylococcus aureus bacteraemia in Thuringia (SUPPORT): a study protocol of a cluster-randomised crossover trial.

INTRODUCTION: Staphylococcus aureus bacteraemia (SAB) is a frequent infection with high mortality rates. It requires specific diagnostic and therapeutic management such as prolonged intravenous administration of antibiotics and aggressive search for and control of infectious sources. Underestimation of disease severity frequently results in delayed or inappropriate management of patients with SAB leading to increased mortality rates. According to observational studies, patient counselling by infectious disease consultants (IDC) improves survival and reduces the length of hospital stay as well as complication rates. In many countries, IDC are available only in some tertiary hospitals. In this trial, we aim to demonstrate that the outcome of patients with SAB in small and medium size hospitals that do not employ IDC can be improved by unsolicited ID phone counselling. The SUPPORT trial will be the first cluster-randomised controlled multicentre trial addressing this question. METHODS AND ANALYSIS: SUPPORT is a single-blinded, multicentre interventional, cluster-randomised, controlled crossover trial with a minimum of 15 centres that will include 250 patients with SAB who will receive unsolicited IDC counselling and 250 who will receive standard of care. Reporting of SAB will be conducted by an electronic real-time blood culture registry established for the German Federal state of Thuringia (ALERTSNet) or directly by participating centres in order to minimise time delay before counselling. Mortality, disease course and complications will be monitored for 90 days with 30-day all-cause mortality rates as the primary outcome. Generalised linear mixed modelling will be used to detect the difference between the intervention sequences. We expect improved outcome of patients with SAB after IDC. ETHICS AND DISSEMINATION: We obtained ethics approval from the Ethics committee of the Jena University Hospital and from the Ethics committee of the State Chamber of Physicians of Thuringia. Results will be published in a peer-reviewed journal and additionally disseminated through public media. TRIAL REGISTRATION NUMBER: DRKS00010135.

Should daptomycin-rifampin combinations for MSSA/MRSA isolates be avoided because of antagonism?

PURPOSE: There is increasing clinical evidence from observational studies, that combination therapy of daptomycin with rifampin is a valuable treatment option for biofilm-associated difficult to treat Staphylococcus aureus infections such as osteomyelitis, prosthetic joint infection and endocarditis. However, two studies analyzing a limited number of S. aureus isolates reported an antagonism of those two drugs questioning the benefit of this combination. METHODS: To estimate the frequency of this possible antagonism, we performed in vitro checkerboard assays on 58 consecutive clinical isolates of S. aureus (MSSA n = 9, MRSA n = 49). We determined the fractional inhibitory concentration index (FICI) and the susceptible breakpoint index (SBPI). All isolates were characterized by a microprobe array detecting 336 different genes/alleles to ensure their non-clonal origin. RESULTS: For all isolates, the FICI was between 1.00 and 1.25 indicating additive effects for the daptomycin/rifampin combination. Neither antagonism nor synergism as defined by the FICI was found for any of the isolates. CONCLUSION: Based on these data, there is no evidence to advise against the daptomycin/rifampin combination therapy.

Menstrual cycle effects on selective attention and its underlying cortical networks.

It was the aim of the present study to investigate menstrual cycle effects on selective attention and its underlying functional cerebral networks. Twenty-one healthy, right-handed, normally cycling women were investigated by means of functional magnetic resonance imaging using a go/no-go paradigm during the menstrual, follicular and luteal phase. On the behavioral level there was a significant interaction between visual half field and cycle phase with reaction times to right-sided compared to left-sided stimuli being faster in the menstrual compared to the follicular phase. These results might argue for a more pronounced functional cerebral asymmetry toward the left hemisphere in selective attention during the menstrual phase with low estradiol and progesterone levels. Functional imaging, however, did not reveal clear-cut menstrual phase-related changes in activation pattern in parallel to these behavioral findings. A functional connectivity analysis identified differences between the menstrual and the luteal phase: During the menstrual phase, left inferior parietal cortex showed a stronger negative correlation with the right middle frontal gyrus while the left medial frontal cortex showed a stronger negative correlation with the left middle frontal gyrus. These results can serve as further evidence of a modulatory effect of steroid hormones on networks of lateralized cognitive functions not only by interhemispheric inhibition but also by affecting intrahemispheric functional connectivity.

Autophagy in the brain of neonates following hypoxia-ischemia shows sex- and region-specific effects.

Autophagy is responsible for the bulk degradation of cytoplasmic contents including organelles through the lysosomal machinery. Neonatal hypoxia-ischemia (HI) causes cell death in the brain by caspase-dependent and independent pathways. Ischemic insults also increase the formation of autophagosomes and activate autophagy. This study assessed the possible sex- and region-specific differences of autophagy activity in neonates subjected to HI brain injury. HI males had a modest decrease in lysosome numbers with no effect on LC3B-II protein in the cortex. In contrast, HI females had decreased lysosome numbers and their LC3B-II protein expression was significantly increased in the cortex following HI. In the hippocampus, both HI males and all females had increased numbers of autolysosomes suggesting activation of autophagy but with no effect on lysosome numbers, or Beclin-1 or LC3B protein levels. Males and females had increases in caspase 3/7 activity in their cortices and hippocampi following HI, though the increases were three to sixfold greater in females. The present data: (a) confirm greater caspase activation in the brains of females compared to males following HI; (b) suggest a partial failure to degrade LC3B-II protein in cortical but not hippocampal lysosomes of females as compared to males following neonatal HI; (c) all females have greater basal autophagy activity than males which may protect cells against injury by increasing cell turnover and (d) demonstrate that autophagy pathways are disturbed in regional- and sex-specific patterns in the rat brain following neonatal HI.

Relative survival of patients with non-malignant central nervous system tumours: a descriptive study by the Austrian Brain Tumour Registry.

BACKGROUND: Unlike malignant primary central nervous system (CNS) tumours outcome data on non-malignant CNS tumours are scarce. For patients diagnosed from 1996 to 2002 5-year relative survival of only 85.0% has been reported. We investigated this rate in a contemporary patient cohort to update information on survival. METHODS: We followed a cohort of 3983 cases within the Austrian Brain Tumour Registry. All patients were newly diagnosed from 2005 to 2010 with a histologically confirmed non-malignant CNS tumour. Vital status, cause of death, and population life tables were obtained by 31 December 2011 to calculate relative survival. RESULTS: Overall 5-year relative survival was 96.1% (95% CI 95.1-97.1%), being significantly lower in tumours of borderline (90.2%, 87.2-92.7%) than benign behaviour (97.4%, 96.3-98.3%). Benign tumour survival ranged from 86.8 for neurofibroma to 99.7% for Schwannoma; for borderline tumours survival rates varied from 83.2 for haemangiopericytoma to 98.4% for myxopapillary ependymoma. Cause of death was directly attributed to the CNS tumour in 39.6%, followed by other cancer (20.4%) and cardiovascular disease (15.8%). CONCLUSION: The overall excess mortality in patients with non-malignant CNS tumours is 5.5%, indicating a significant improvement in survival over the last decade. Still, the remaining adverse impact on survival underpins the importance of systematic registration of these tumours.

[Clostridium difficile infection (CDI) in the course of time - an issue only for the internist?]. / Clostridium-difficile-Infektionen (CDI) im Wandel der Zeit - ein Thema nur für den Internisten?

BACKGROUND: Toxigenic strains of Clostridium (C.) difficile are the most prevalent pathogens of antibiotic associated intestinal disease and nosocomial diarrhoea. During the last 10 years, incidences of C. difficile infection (CDI) have increased worldwide. MATERIALS AND METHODS: With clinical and microbiological original data for 2002-2012 from the University Hospitals Leipzig and Halle (Saale), Germany, the authors illustrate the current situation regarding CDI in the states of Saxony and Saxony-Anhalt and exemplify the latest developments in terms of incidence, prevalence of resistance, diagnosis and treatment strategies regarding CDI with an emphasis on surgical options. RESULTS: Following the general trend, at the University Hospitals of Leipzig and Halle (Saale) there was also an increase in incidence of CDI, especially of severe clinical courses. In primary and secondary care facilities, prevention of CDI is based on hygiene management and restricted usage of antibiotics, preferably as "Antibiotic Stewardship" programmes. In 2012, the new macrocyclic antibiotic Fidaxomicin was approved in the European Union for the treatment of CDI. The therapeutic armamentarium, previously based on metronidazole or vancomycin, has now been enriched by a substance that presumably will reduce the rate of recurrence of CDI. Moreover, early data from case series and controlled trials suggest that the re-establishment of eubiosis in the colon of patients with recurrent CDI by stool transplantation from healthy donors is an alternative to antibiotics. Standard surgical intervention for refractory CDI is subtotal colectomy with terminal ileostomy. In patients with adequate life expectancy and without organ dysfunction, a colon-saving surgical technique should be considered. CONCLUSION: Taking antibiotics for most remains the main risk factor for suffering from symptomatic CDI. With the introduction of Fidaxomicin there is hope for an improvement in the conservative treatment of CDI. Stool transplants from healthy donors are now considered to be better than giving antibiotics for severe CDI, but this treatment has not found broad acceptance yet. In cases with a lack of early treatment success, the surgeon must be consulted. Here, the evidence for preferably colon-saving surgical procedures is so far unfortunately low.

[Drug therapy of infectious diarrhea: part 1: acute diarrhea]. / Medikamentöse Therapie der infektiösen Diarrhö: Teil 1: akute Diarrhö

BACKGROUND: Diarrhea is one of the most commonly occurring diseases. AIM: This article gives a review of the current state of the treatment of acute infectious diarrhea (part 1) and chronic infectious diarrhea (part 2) as well as of the most important pathogens. MATERIAL AND METHODS: Following a presentation of the general principles of the therapy of diarrhea, the targeted antimicrobial therapy of the most important bacterial gastrointestinal infections is described. This includes salmonellosis, shigellosis and Campylobacter infections, infections with pathogenic Escherichia coli strains, yersiniosis and cholera. Due to the increasing incidence and changes in the severity of the disease and important new aspects in the treatment of diarrhea caused by toxigenic Clostridium difficile strains, these disease entities will be described in detail. RESULTS: Symptomatic therapy is still the most important aspect of the treatment of infectious diarrhea. For severely ill patients with a high frequency of stools (> 8/day), immunodeficiency, advanced age or significant comorbidities, empirical antibiotic therapy should be considered. Increasing resistance, in particular against fluoroquinolones must also be taken into consideration. Due to the risk of excessive pathogen proliferation and concomitant intestinal toxin production with protracted or multiple complications during the disease, therapy with motility inhibitors is not recommended. With respect to the treatment of Clostridium difficile infections a promising novel aspect arose in 2012. The macrocyclic antibiotic fidaxomycin can reduce the rate of recurrent disease with the same effectiveness as vancomycin. Furthermore, evidence for the benefits of allogenic stool transplantation is increasing. CONCLUSION: The treatment of acute diarrhea is still primarily supportive. The benefits of general empirical antibiotic therapy for acute diarrhea are not evidence-based.

[Drug therapy of infectious diarrhea. Part 2: Chronic diarrhea]. / Medikamentöse Therapie der infektiösen Diarrhö. Teil 2: Chronische Diarrhö.

Diarrheal diseases are among the most common diseases worldwide. In this review the current treatment recommendations for acute (Part 1) and chronic (Part 2) infectious diarrhea are summarized and typical enteropathogens are discussed. The second part of the article describes chronic diarrhea, its related pathogens and treatment. In contrast to acute diarrhea which is mainly caused by viral and typical bacterial pathogens, chronic diarrhea has mainly non-infectious origins. Protozoal pathogens, such as Giardia lamblia and Entamoeba histolytica in particular are found and more rarely bacterial pathogens, such as Tropheryma whipplei. Opportunistic pathogens cause diarrhea in immunocompromised patients, such as in HIV patients. In these patients cytomegalovirus (CMV) colitis or infections with Cryptosporidium spp., Cyclospora cayetanensis, Isospora belli or microsporidia have to be considered. Besides targeted specific antimicrobial therapy, anti-retroviral drugs improving the underlying immunosuppression and thus the reconstitution of the adaptive immune response remain a cornerstone of the treatment in HIV-positive patients.

[Immunosuppressive treatment as a risk factor for the occurrence of clostridium difficile infection (CDI)]. / Immunsuppressive Behandlung als Risikofaktor für das Auftreten einer Clostridium-difficile-Infektion (CDI).

BACKGROUND: Toxigenic Clostridium difficile strains are known as the most common infectious cause of antibiotic-associated intestinal disease and nosocomial diarrhoea. The increased incidence of hypervirulent strains gives rise to worldwide concern. In particular, courses with multiple recurrences are observed in the presence of immunosuppression. METHODS: In this retrospective controlled observational study we aimed to determine immunosuppression as an independent risk factor for symptomatic CDI and to identify characteristics and differences of immunocompromised patients with respect to disease severity, disease progression, intestinal manifestations, recurrence rates and other factors. We compared symptoms and clinical features of 55 immunosuppressed patients with confirmed CDI with those of 50 patients without immunosuppressive medication (mean age 59.3 years ±â€Š16.2 vs. 69.2 years ±â€Š15.0) who were treated at the Departments of Internal Medicine I and IV of the University Hospital Halle (Saale), Germany, between 2006 and 2009. Multivariate analysis using binary logistic regression was performed for a control group of 105 patients without CDI. In this group, there were 62 patients without evidence of immunosuppression and 43 immunosuppressed patients (mean age 66.9 years ±â€Š12.4 vs. 56.0 years ±â€Š13.7). RESULTS: The clinical courses of the two groups differed considerably. Immunosuppressed patients were significantly more frequently colonised with Clostridium difficile without clinically detectable manifestation or only mild clinical symptoms not requiring therapy (22 vs. 2 %, p = 0.003), while there were similar numbers of moderate (46 vs. 52 %, p = 0.503) but less severe CDI cases (27 vs. 40 %, p = 0.167). Relapses were observed more frequently in the group of immunosuppressed patients (15 vs. 6 %, p = 0.153). Multivariate analysis using logistic regression identified immunosuppression as an independent risk factor for CDI (OR = 2.75), in addition to prior antibiotic therapy (OR = 10.15) and PPI intake (OR = 2.93). CONCLUSION: We conclude that immunosuppression has to be regarded as an independent risk factor for CDI. Immunosuppressive treatment increases the risk of colonisation and infection with Clostridium difficile and leads to a higher relapse rate in patients with CDI.

Emotional prosody modulates attention in schizophrenia patients with hallucinations.

Recent findings have demonstrated that emotional prosody (EP) attracts attention involuntarily (Grandjean et al., 2008). The automat shift of attention toward emotionally salient stimuli can be overcome by attentional control (Hahn et al., 2010). Attentional control is impaired in schizophrenia, especially in schizophrenic patients with hallucinations because the "voices" capture attention increasing the processing load and competing for top-down resources. The present study investigates how involuntary attention is driven by implicit EP in schizophrenia with auditory verbal hallucinations (AVH) and without (NAVH). Fifteen AVH patients, 12 NAVH patients and 16 healthy controls (HC) completed a dual-task dichotic listening paradigm, in which an emotional vocal outburst was paired with a neutral vocalization spoken in male and female voices. Participants were asked to report the speaker's gender while attending to either the left or right ear. NAVH patients and HC revealed shorter response times for stimuli presented to the attended left ear than the attended right ear. This laterality effect was not present in AVH patients. In addition, NAVH patients and HC showed faster responses when the EP stimulus was presented to the unattended ear, probably because of less interference between the attention-controlled gender voice identification task and involuntary EP processing. AVH patients did not benefit from presenting emotional stimuli to the unattended ear. The findings suggest that similar to HC, NAVH patients show a right hemispheric bias for EP processing. AVH patients seem to be less lateralized for EP and therefore might be more susceptible to interfering involuntary EP processing; regardless which ear/hemisphere receives the bottom up input.