[Care trajectories of homeless or precariously housed mentally ill patients from two psychiatric-psychotherapeutic hospitals in North Rhine-Westphalia]. / Versorgungstrajektorien wohnungsloser oder in prekären Wohnverhältnissen lebender psychisch Erkrankter zweier psychiatrisch-psychotherapeutischer Kliniken der Regelversorgung Nordrhein-Westfalens.

OBJECTIVES: Mental illness and homelessness are often associated with each other. The study aim was to describe the care trajectories of psychiatric inpatients admitted from precarious housing or homelessness. METHODS: An anonymized data collection was performed at two psychiatric hospitals in North Rhine-Westphalia. RESULTS: Of 76 identified patients, every other was discharged to unsecured housing or homelessness. An unresolved housing situation delayed discharge in almost every third case. Upon discharge outpatient somatic or psychiatric treatment was not secured in more than 30%, and in more than 40% of cases, resp. CONCLUSION: Improvement of the housing situation is possible in a minority of cases for psychiatric inpatients admitted from unsecured housing. The unresolved housing situation was seen as an obstacle to discharge in every third case.

[Patient satisfaction with psychiatric day-care and inpatient treatment: Effects on physical and mental health]. / Zufriedenheit mit (teil-)stationärer psychiatrischer Behandlung: Effekte auf die physische und psychische Gesundheit.

INTRODUCTION: Quality assessment from the patient's point of view makes it possible to identify negative quality developments at an early stage. The focus is not on the medical result, but on what the patient wants. Correlations between patient satisfaction and physical and psychological treatment outcome were already shown in the 1990s. However, studies using rather unspecific satisfaction measures are scarce. The aim of this study was to investigate the influence of patient satisfaction with the treatment and the therapies offered on the extent of recovery. METHODS: In this prospective study, a questionnaire developed for the differentiated recording of patient satisfaction with the therapy offerings of the LWL-Klinik Dortmund was used in a day-care/hospital setting. The structure of the questionnaire was tested by means of explorative factor analysis. The factors generated in this way served as the basis for the hierarchical regression analyses in the further course. In addition to important treatment aspects from the patient's point of view, the subjective health status was recorded by means of SF-36. RESULTS: 105 patients participated in the study (64% female, 84% diagnosed with depression). Significant predictors for physical health were well-being after exercise therapy and satisfaction with the weekly structure of services. Significant predictors for mental health were age at onset of illness, age, perceived benefits from exercise therapy as well as occupational therapy, treatment duration and setting. DISCUSSION: The demonstrated impact of patient satisfaction on mental health highlights the relevance of treatment quality improvement to recovery.

Treatment of Bipolar Disorders in Older Adults: A Review.

Background: Old age bipolar disorder has been an orphan of psychiatric research for a long time despite the fact that bipolar disorder (BD)-I and II together may affect 0.5-1.0% of the elderly. It is also unclear whether aetiology, course of illness and treatment should differ in patients with a first manifestation in older age and patients suffering from a recurrence of a BD known for decades. This narrative review will summarize the current state of knowledge about the epidemiology, clinical features, and treatment of BD in the elderly. Methods: We conducted a Medline literature search from 1970 to 2021 using MeSH terms "Bipolar Disorder" × "Aged" or "Geriatric" or "Elderly". Search results were complemented by additional literature retrieved from examining cross references and by hand search in text books. Summary of findings: Varying cut-off ages have been applied to differentiate old age from adult age BD. Within old age BD, there is a reasonable agreement of distinct entities, early and late-onset BD. They differ to some extent in clinical symptoms, course of illness, and some co-morbidities. Point prevalence of BD in older adults appears slightly lower than in working-age adults, with polarity of episodes shifting towards depression. Psychopharmacological treatment needs to take into account the special aspects of somatic gerontology and the age-related change of pharmacokinetic and pharmacodynamic characteristics. The evidence for commonly used treatments such as lithium, moodstabilizing antiepileptics, antipsychotics, and antidepressants remains sparse. Preliminary results support a role of ECT as well as psychotherapy and psychosocial interventions in old age BD. Conclusions: There is an obvious need of further research for all treatment modalities of BD in old age. The focus should be pharmacological and psychosocial approaches, as well as their combination, and the role of physical treatment modalities such as ECT.Appeared originally in Ann Gen Psychiatry 2021; 20:1.

Homelessness among psychiatric inpatients in North Rhine-Westphalia: a retrospective routine data analysis.

BACKGROUND: Within the last five years the number of homeless persons in Germany has more than doubled, with many suffering from mental illnesses that require treatment. Whether the mental illness itself led to losing shelter or whether the state of being homeless increased the likelihood of developing symptoms of a mental disorder remains unclear. The current study assessed the interaction of homelessness and mental illness from a care provider perspective. METHODS: We conducted a retrospective analysis of inpatient routine data from 20 psychiatric hospitals in North Rhine-Westphalia (NRW), Germany, over a period of four years (N = 366,767 inpatient treatment cases). Patients were considered "homeless" if they had no fixed unique address. RESULTS: About 2.4% of the analyzed cohort was classified as homeless, with increasing tendency over the study period (+14% from 2016 to 2019). The percentage of homeless patients varied broadly between the hospitals (0.2-6.3%). Homeless patients were more often male and on average eight years younger than patients with a fixed address. Homeless patients experienced more involuntary measures (admission and restraint), had a shorter course of treatment and were more often discharged within one day. Every second homeless case was diagnosed with a substance use disorder and every third homeless case with a psychotic disorder, whereas affective disorders were diagnosed less frequently in this group. Psychiatric comorbidity occurred more often in homeless patients whereas somatic diseases did not. CONCLUSIONS: Multiple patient-related sociodemographic and local factors are associated with homelessness of psychiatric inpatients. In addition, clinical factors differ between homeless and non-homeless patients, pointing to more severe mental illness and treatment complications (e.g., coercive measures) in homeless persons. Thus, homelessness of psychiatric inpatients can imply special challenges that need to be considered by healthcare providers and politicians, with the goal of optimizing mental and social care and the mental health outcomes of homeless persons.

A new electronically based clinical pathway for schizophrenia inpatients: A longitudinal pilot study.

Patients with schizophrenia, a severe chronic disorder, are characterized by resistance to therapy, lack of disease understanding, non-compliance and non-adherence, partly caused and maintained by an often poorly structured treatment strategy and polypharmacy. Treatment pathways in the sense of decision aids for professionals bring recommendations from guidelines into a clear and practice-oriented algorithm that can be a helpful tool for treatment. The aim of the present study was to assess the impact of a newly developed electronic clinical pathway (CPW) that integrates the standard computerized medical report system on symptomatic outcomes and process parameters in a population of inpatients with schizophrenia. In this randomized single-center study, 156 patients with schizophrenic disorder were treated in two groups: an experimental CPW group and a control "treatment as usual" (TAU) group. The treatment improvement was analyzed using various process parameters: the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression scale (CGI), the Personal and Social Performance scale (PSP) and the Nurses' Observation Scale for Inpatient Evaluation (NOSIE). The CPW patients differentially showed greater improvement in psychopathology (PANSS) compared to TAU patients (t(154) = 2.030, p = 0.044). There also seems to be advantage for CPW concerning improvement in NOSIE. These results indicate a positive influence of CPW on the quality of treatment and support its implementation in daily clinical practice.

Treatment of bipolar disorders in older adults: a review.

BACKGROUND: Old age bipolar disorder has been an orphan of psychiatric research for a long time despite the fact that bipolar disorder (BD)-I and II together may affect 0.5-1.0% of the elderly. It is also unclear whether aetiology, course of illness and treatment should differ in patients with a first manifestation in older age and patients suffering from a recurrence of a BD known for decades. This narrative review will summarize the current state of knowledge about the epidemiology, clinical features, and treatment of BD in the elderly. METHODS: We conducted a Medline literature search from 1970 to 2021 using MeSH terms "Bipolar Disorder" × "Aged" or "Geriatric" or "Elderly". Search results were complemented by additional literature retrieved from examining cross references and by hand search in text books. Varying cut-off ages have been applied to differentiate old age from adult age BD. Within old age BD, there is a reasonable agreement of distinct entities, early and late-onset BD. They differ to some extent in clinical symptoms, course of illness, and some co-morbidities. Point prevalence of BD in older adults appears slightly lower than in working-age adults, with polarity of episodes shifting towards depression. Psychopharmacological treatment needs to take into account the special aspects of somatic gerontology and the age-related change of pharmacokinetic and pharmacodynamic characteristics. The evidence for commonly used treatments such as lithium, mood-stabilizing antiepileptics, antipsychotics, and antidepressants remains sparse. Preliminary results support a role of ECT as well as psychotherapy and psychosocial interventions in old age BD. CONCLUSIONS: There is an obvious need of further research for all treatment modalities of BD in old age. The focus should be pharmacological and psychosocial approaches, as well as their combination, and the role of physical treatment modalities such as ECT.

Consequences of exposure to the thin ideal in mass media depend on moderators in young women: An experimental study.

This study examined the consequences of media exposure to thin ideals compared to pictures of landscapes in healthy young women and women with eating and mixed mental disorders and investigated whether appearance-related cognitive factors and cognitive distortions moderate the effects. Two hundred seventy-five women in a multisite laboratory trial (174 in- or outpatients and 101 healthy women; Mage 22.87 years, SD = 3.94) were exposed to either thin ideals or to landscape pictures and guided through a vivid imagery of these pictures thereafter. Changes in body image dissatisfaction, mood, eating behavior, and physiological markers were assessed. After thin ideal exposure and even more after guided imagery, women's body image dissatisfaction increased and mood declined. The effect on mood was most pronounced in women with eating disorders, less in women with mixed disorders, and smallest in healthy controls. No effects were found on physiological measures. Higher values of appearance-related cognitive factors moderated the effect of thin ideal exposure and guided imagery on all psychological outcomes. Cognitive distortions moderated the effect of thin ideal exposure and guided imagery on mood. Findings indicate an overall susceptibility to viewing thin ideal pictures in magazines in young and especially in women with eating disorders. Though exposure in the laboratory resulted in psychological effects, it did not lead to a physiological stress response. The impact of thin ideal exposure on mood is in line with affect-regulation models in eating disorders, with appearance-related cognitive factors and cognitive distortions potentially accelerating such effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Role of child maltreatment and gender for bipolar symptoms in young adults.

BACKGROUND: Child maltreatment has been shown to be associated with a wide range of mental disorders, including bipolar disorders. In this 2-year follow-up study, recollections of emotional, physical and sexual abuse were related to bipolar symptoms, namely depressive, hypomanic and manic symptoms. METHODS: The sample consists of 134 students who took part at five measurement times within the 2-year period. Data were collected with self-report scales. RESULTS: The results show that recollections of abuse, particularly emotional abuse, were associated with more severe depressive symptoms; this finding, however, only applied to women. Hypomanic and manic symptoms were not associated with recollections of abuse. For hypomanic symptoms, however, a significant decrease over the 2 years was observed. CONCLUSIONS: The findings of this study suggest that recollections of abusive experiences in childhood combined with female gender increase the risk for depression, whereas hypomanic and manic states are probably better predicted by other factors, such as current life circumstances.

Drug-Induced Liver Injury (DILI) in Patients with Depression Treated with Antidepressants: A Retrospective Multicenter Study.

INTRODUCTION: Drug-induced liver injury (DILI) is the 4th most common cause of liver damage in Western countries and can be caused by antidepressants. METHODS: Against the background of increasing antidepressant prescriptions and increasing use of polypharmacy, we analyzed administered antidepressants and other pharmacological substances, liver toxicity, comorbid somatic secondary diseases together with the occurrence of DILI in a patient population of 6 centers throughout Germany. RESULTS: The majority of the enrolled 329 patients received polypharmacological treatment in an inpatient setting. During antidepressant treatment 5.1% of the patients had elevated serum transaminase levels, whereby exactly and not more than 1 criterion proposed to be indicative for DILI, was fulfilled by 3 patients (0.9%). DISCUSSION: During patient characterization it becomes clear that a sensitization for relevant risk constellations causing liver injury in MDD patients is relevant to prevent further serious adverse events.

The social-psychiatric service and its role in compulsory hospitalization.

Coercive measures are a sensitive, much-discussed ethical and legal issue in the psychiatric context. Hence, the identification of their predictors and ways of prevention are of utmost importance. The present study aimed to determine the impact of the social-psychiatric services (SPS) in North Rhine Westphalia (NRW) on involuntary admissions according to the German Mental Health Act and to identify predictors for the reduction of these involuntary admissions. A dataset including details from 31 districts and 23 towns in NRW over a time period of 10 years (2005-2014) was analysed regarding the number of involuntary admissions, gender and age of admitted patients, and person/institution initiating the compulsory act. All 56 SPS in NRW were contacted for information on the number of clients/contacts, home visits, areas of responsibility and their involvement in involuntary admissions. Thirty SPS participated in the survey. We found a significant increase of involuntary admissions over time with significantly higher proportions of male patients and patients younger than 60 years in every year. Regarding the characteristics of SPS, a negative correlation between the number of clients contacting the SPS on their own initiative and low-income households was observed. Additionally, the number of clients contacting the SPS on their own initiative was significantly higher in districts/towns associated with lower involuntary admission rates. These data suggest that patient-based factors were of great importance in the context of involuntary admissions. Furthermore, the SPS and home treatment should be strengthened and intensified to achieve lower involuntary admission rates.

Ward Atmosphere and Patient Satisfaction in Psychiatric Hospitals With Different Ward Settings and Door Policies. Results From a Mixed Methods Study.

Background: Open-door policies in psychiatry are discussed as a means to improve the treatment of involuntarily committed patients in various aspects. Current research on open-door policies focuses mainly on objective effects, such as the number of coercive interventions or serious incidents. The aim of the present study was to investigate more subjective perceptions of different psychiatric inpatient settings with different door policies by analyzing ward atmosphere and patient satisfaction. Methods: Quantitative data on the ward atmosphere using the Essen Climate Evaluation Scale (EssenCES) and on patient satisfaction (ZUF-8) were obtained from involuntarily committed patients (n = 81) in three psychiatric hospitals with different ward settings and door policies (open, facultative locked, locked). Furthermore, qualitative interviews with each of 15 patients, nurses, and psychiatrists were conducted in one psychiatric hospital with a facultative locked ward comparing treatment in an open vs. a locked setting. Results: Involuntarily committed patients rated the EssenCES' subscale "Experienced Safety" higher in an open setting compared with a facultative locked and a locked setting. The subscale "Therapeutic Hold" was rated higher in an open setting than a locked setting. Regarding the safety experienced from a mental health professionals' perspective, the qualitative interviews further revealed advantages and disadvantages of door locking in specific situations, such as short-term de-escalation vs. increased tension. Patient satisfaction did not differ between the hospitals but correlated weakly with the EssenCES' subscale "Therapeutic Hold." Conclusion: Important aspects of the ward atmosphere seem to be improved in an open vs. a locked setting, whereas patient satisfaction does not seem to be influenced by the door status in the specific population of patients under involuntary commitment. The ward atmosphere turned out to be more sensitive to differences between psychiatric inpatient settings with different door policies. It can contribute to a broader assessment by including subjective perceptions by those who are affected directly by involuntary commitments. Regarding patient satisfaction under involuntary commitment, further research is needed to clarify both the relevance of the concept and its appropriate measurement.

Facial Emotion Recognition Abilities in Women Experiencing Eating Disorders.

OBJECTIVE: Impairments in facial emotion recognition are an underlying factor of deficits in emotion regulation and interpersonal difficulties in mental disorders and are evident in eating disorders (EDs). METHODS: We used a computerized psychophysical paradigm to manipulate parametrically the quantity of signal in facial expressions of emotion (QUEST threshold seeking algorithm). This was used to measure emotion recognition in 308 adult women (anorexia nervosa [n = 61], bulimia nervosa [n = 58], healthy controls [n = 130], and mixed mental disorders [mixed, n = 59]). The M (SD) age was 22.84 (3.90) years. The aims were to establish recognition thresholds defining how much information a person needs to recognize a facial emotion expression and to identify deficits in EDs compared with healthy and clinical controls. The stimuli included six basic emotion expressions (fear, anger, disgust, happiness, sadness, surprise), plus a neutral expression. RESULTS: Happiness was discriminated at the lowest, fear at the highest threshold by all groups. There were no differences regarding thresholds between groups, except for the mixed and the bulimia nervosa group with respect to the expression of disgust (F(3,302) = 5.97, p = .001, η = .056). Emotional clarity, ED pathology, and depressive symptoms did not predict performance (RChange ≤ .010, F(1,305) ≤ 5.74, p ≥ .079). The confusion matrix did not reveal specific biases in either group. CONCLUSIONS: Overall, within-subject effects were as expected, whereas between-subject effects were marginal and psychopathology did not influence emotion recognition. Facial emotion recognition abilities in women experiencing EDs compared with women experiencing mixed mental disorders and healthy controls were similar. Although basic facial emotion recognition processes seems to be intact, dysfunctional aspects such as misinterpretation might be important in emotion regulation problems. CLINICAL TRIAL REGISTRATION NUMBER: DRKS-ID: DRKS00005709.

Self-reported emotion regulation difficulties are associated with mood but not with the biological stress response to thin ideal exposure.

BACKGROUND: Difficulties in emotion regulation have been related to psychological and physiological stress responses such as lower mood and lower parasympathetic activation (HF-HRV) under resting condition, but evidence on the potential link to the hypothalamic-pituitary-adrenal (HPA) axis functioning and to physiological stress responses during a stress task is still scarce. The aim of the study was to investigate stress responses in young women when confronted to a daily stressor such as exposure to thin ideals and to understand the role of correlates of self-reported trait-like emotion regulation difficulties (ERD). METHODS: Heart rate variability (HRV) and salivary cortisol data were collected in a sample of 273 young women aged 18-35 with and without mental disorders during a vivid imagination of thin ideals (experimental condition) or landscapes (control condition). Changes in mood states were measured on a visual analogue scale (0-100). Correlates of trait-like ERD were self-reported using the Difficulties in Emotion Regulation Scale (DERS). RESULTS: Participants with higher ERD showed a stronger decline in self-reported mood after vivid imagination of thin ideals compared to participants with lower ERD in the experimental condition but also a stronger increase of positive mood with increasing ERD in the control condition. ERD were not related to baseline HF-HRV or baseline salivary cortisol levels nor to any physiological response during and after the imagination of thin ideals. DISCUSSION AND CONCLUSION: The results corroborate the role of ERD regarding the immediate psychological impact of daily stressors. Exposition to daily stressors in the laboratory results in discrepant psychological and physiological reactivity. Future studies should investigate under what conditions the complex interrelations between immediate and long-term ERD and biological activation are amenable to assessment in a laboratory setting. The additive effects of multiple exposition to stressors, such as thin ideals in daily life, also need to be addressed.

Streptococcus pneumoniae triggers progression of pulmonary fibrosis through pneumolysin.

RATIONALE: Respiratory tract infections are common in patients suffering from pulmonary fibrosis. The interplay between bacterial infection and fibrosis is characterised poorly. OBJECTIVES: To assess the effect of Gram-positive bacterial infection on fibrosis exacerbation in mice. METHODS: Fibrosis progression in response to Streptococcus pneumoniae was examined in two different mouse models of pulmonary fibrosis. MEASUREMENTS AND MAIN RESULTS: We demonstrate that wild-type mice exposed to adenoviral vector delivery of active transforming growth factor-ß1 (TGFß1) or diphteria toxin (DT) treatment of transgenic mice expressing the DT receptor (DTR) under control of the surfactant protein C (SPC) promoter (SPC-DTR) to induce pulmonary fibrosis developed progressive fibrosis following infection with Spn, without exhibiting impaired lung protective immunity against Spn. Antibiotic treatment abolished infection-induced fibrosis progression. The cytotoxin pneumolysin (Ply) of Spn caused this phenomenon in a TLR4-independent manner, as Spn lacking Ply (SpnΔply) failed to trigger progressive fibrogenesis, whereas purified recombinant Ply did. Progressive fibrogenesis was also observed in AdTGFß1-exposed Ply-challenged TLR4 KO mice. Increased apoptotic cell death of alveolar epithelial cells along with an attenuated intrapulmonary release of antifibrogenic prostaglandin E2 was found to underlie progressive fibrogenesis in Ply-challenged AdTGFß1-exposed mice. Importantly, vaccination of mice with the non-cytotoxic Ply derivative B (PdB) substantially attenuated Ply-induced progression of lung fibrosis in AdTGFß1-exposed mice. CONCLUSIONS: Our data unravel a novel mechanism by which infection with Spn through Ply release induces progression of established lung fibrosis, which can be attenuated by protein-based vaccination of mice.

Dynamics of T-cell IFN-γ and miR-29a expression during active pulmonary tuberculosis.

IFN-γ is crucial for protection against Mycobacterium tuberculosis. miR-29 was recently shown to non-redundantly inhibit IFN-γ. Here, we investigated IFN-γ and miR-29a expression dynamics of CD4(+) T cells from patients during active tuberculosis (TB) (n = 32) and in household contacts who were latently M. tuberculosis infected (n = 19) from Ghana. Whereas M. tuberculosis-specific IFN-γ expression was similar during TB chemotherapy, superantigen stimulation indicated generally impaired IFN-γ expression in TB patients. No interdependency between miR-29a and IFN-γ expression of T cells was observed. However, miR-29a was differentially expressed in T cells during chemotherapy. We concluded that differential miR-29a expression in active TB was not causative for impaired IFN-γ expression.

Are microRNAs suitable biomarkers of immunity to tuberculosis?

BACKGROUND: MicroRNAs (miRNAs) are crucial regulators of human immunity e.g. against Mycobacterium tuberculosis. Against the background of still alarming high mortality of tuberculosis effective biomarkers to improve diagnosis of M. tuberculosis infection and successful treatment are of major importance. CONCLUSIONS: This review summarizes recent surrogate tissue studies for identification of miRNA biomarker candidates in human tuberculosis with a special focus on reproducibility and conformance. In addition we provide assistance for the design of biomarker studies to circumvent major pitfalls.

TNF-related apoptosis-inducing ligand (TRAIL) exerts therapeutic efficacy for the treatment of pneumococcal pneumonia in mice.

Apoptotic death of alveolar macrophages observed during lung infection with Streptococcus pneumoniae is thought to limit overwhelming lung inflammation in response to bacterial challenge. However, the underlying apoptotic death mechanism has not been defined. Here, we examined the role of the TNF superfamily member TNF-related apoptosis-inducing ligand (TRAIL) in S. pneumoniae-induced macrophage apoptosis, and investigated the potential benefit of TRAIL-based therapy during pneumococcal pneumonia in mice. Compared with WT mice, Trail(-/-) mice demonstrated significantly decreased lung bacterial clearance and survival in response to S. pneumoniae, which was accompanied by significantly reduced apoptosis and caspase 3 cleavage but rather increased necrosis in alveolar macrophages. In WT mice, neutrophils were identified as a major source of intraalveolar released TRAIL, and their depletion led to a shift from apoptosis toward necrosis as the dominant mechanism of alveolar macrophage cell death in pneumococcal pneumonia. Therapeutic application of TRAIL or agonistic anti-DR5 mAb (MD5-1) dramatically improved survival of S. pneumoniae-infected WT mice. Most importantly, neutropenic mice lacking neutrophil-derived TRAIL were protected from lethal pneumonia by MD5-1 therapy. We have identified a previously unrecognized mechanism by which neutrophil-derived TRAIL induces apoptosis of DR5-expressing macrophages, thus promoting early bacterial killing in pneumococcal pneumonia. TRAIL-based therapy in neutropenic hosts may represent a novel antibacterial treatment option.

FMS-like tyrosine kinase 3 ligand treatment of mice aggravates acute lung injury in response to Streptococcus pneumoniae: role of pneumolysin.

FMS-like tyrosine kinase-3 ligand (Flt3L) is a dendritic cell (DC) growth and differentiation factor with potential in antitumor therapies and antibacterial immunization strategies. However, the effect of systemic Flt3L treatment on lung-protective immunity against bacterial infection is incompletely defined. Here, we examined the impact of deficient (in Flt3L knockout [KO] mice), normal (in wild-type [WT] mice), or increased Flt3L availability (in WT mice pretreated with Flt3L for 3, 5, or 7 days) on lung DC subset profiles and lung-protective immunity against the major lung-tropic pathogen, Streptococcus pneumoniae. Although in Flt3L-deficient mice the numbers of DCs positive for CD11b (CD11b(pos) DCs) and for CD103 (CD103(pos) DCs) were diminished, lung permeability, a marker of injury, was unaltered in response to S. pneumoniae. In contrast, WT mice pretreated with Flt3L particularly responded with increased numbers of CD11b(pos) DCs and with less pronounced numbers of CD103(pos) DCs and impaired bacterial clearance and with increased lung permeability following S. pneumoniae challenge. Notably, infection of Flt3L-pretreated mice with S. pneumoniae lacking the pore-forming toxin, pneumolysin (PLY), resulted in substantially less lung CD11b(pos) DCs activation and reduced lung permeability. Collectively, this study establishes that Flt3L treatment enhances the accumulation of proinflammatory activated lung CD11b(pos) DCs which contribute to acute lung injury in response to PLY released by S. pneumoniae.

Role of Mincle in alveolar macrophage-dependent innate immunity against mycobacterial infections in mice.

The role of macrophage-inducible C-type lectin Mincle in lung innate immunity against mycobacterial infection is incompletely defined. In this study, we show that wild-type (WT) mice responded with a delayed Mincle induction on resident alveolar macrophages and newly immigrating exudate macrophages to infection with Mycobacterium bovis bacillus Calmette-Guérin (BCG), peaking by days 14-21 posttreatment. As compared with WT mice, Mincle knockout (KO) mice exhibited decreased proinflammatory mediator responses and leukocyte recruitment upon M. bovis BCG challenge, and they demonstrated increased mycobacterial loads in pulmonary and extrapulmonary organ systems. Secondary mycobacterial infection on day 14 after primary BCG challenge led to increased cytokine gene expression in sorted alveolar macrophages of WT mice, but not Mincle KO mice, resulting in substantially reduced alveolar neutrophil recruitment and increased mycobacterial loads in the lungs of Mincle KO mice. Collectively, these data show that WT mice respond with a relatively late Mincle expression on lung sentinel cells to M. bovis BCG infection. Moreover, M. bovis BCG-induced upregulation of C-type lectin Mincle on professional phagocytes critically shapes antimycobacterial responses in both pulmonary and extrapulmonary organ systems of mice, which may be important for elucidating the role of Mincle in the control of mycobacterial dissemination in mice.

Expression of the proliferation marker Ki-67 associates with tumour staging and clinical outcome in differentiated thyroid carcinomas.

OBJECTIVE: Although the prognosis of differentiated thyroid carcinoma (DTC) is excellent, with 10-year survival rates of about 90%, about one-third of patients experiences recurrent disease. We aimed to identify novel histological prognostic factors to optimize treatment and follow-up of patients at risks. DESIGN: Retrospective analysis of patients diagnosed from January 1990 to March 2004. SUBJECTS: A total of 93 patients diagnosed with DTC of which 67 with papillary and 26 with follicular histology. MEASUREMENTS: Analysis of immunohistochemical expression of somatostatin receptor (sst) subtypes 1-5, glucose transporter-1 (GLUT-1), receptor tyrosine kinase c-KIT, oestrogen and progesterone receptors, and proliferation marker Ki-67 and correlation with the patients' clinical outcome. RESULTS: DTC showed immunohistochemical expression of GLUT-1, C-KIT and progesterone receptor in a high percentage of cases (range: 57-80%). In contrast, the oestrogen receptor as well as the sst subtypes 1-5 was less frequently detected (range: 15-29%). Mean staining of the proliferation marker Ki-67 was 6% positive cells (range 0-20%). Ki-67 expression was significantly associated with tumour staging (ρ = 0·2076, P = 0·0459), whereas the other histopathological markers were not associated with gender, age, tumour entity, or tumour classification. Tumour staging and expression of Ki-67, oestrogen receptor and sst2, but of none of the other histopathological factors, independently predicted the clinical outcome 5 years after definitive treatment (P < 0·0001, P < 0·0001, P = 0·0004 and P = 0·0206, respectively). CONCLUSIONS: In patients with DTC, Ki-67 expression associates with tumour staging and clinical outcome.