How effective is simple mechanical wound debridement in reducing bacterial colonisation? Results of a prospective clinical study.

BACKGROUND AND AIMS: Bacteria in wounds can lead to stagnation of wound healing as well as to local or even systemic wound infections up to potentially lethal sepsis. Consequently, the bacterial load should be reduced as part of wound treatment. Therefore, the efficacy of simple mechanical wound debridement should be investigated in terms of reducing bacterial colonisation. PATIENTS AND METHODS: Patients with acute or chronic wounds were assessed for bacterial colonisation with a fluorescence camera before and after mechanical wound debridement with sterile cotton pads. If bacterial colonisation persisted, a second, targeted wound debridement was performed. RESULTS: A total of 151 patients, 68 (45.0%) men and 83 (55.0%) women were included in this study. The male mean age was 71.0 years and the female 65.1 years. By establishing a new analysis method for the image files, we could document that the bacterial colonised areas were distributed 21.9% on the wound surfaces, 60.5% on the wound edges (up to 0.5 cm) and 17.6% on the wound surroundings (up to 1.5 cm). One mechanical debridement achieved a significant reduction of bacterial colonised areas by an average of 29.6% in the wounds, 18.9% in the wound edges and 11.8% in the wound surroundings and was increased by performing it a second time. CONCLUSIONS: It has been shown that even a simple mechanical debridement with cotton pads can significantly reduce bacterial colonisation without relevant side effects. In particular, the wound edges were the areas that were often most contaminated with bacteria and should be included in the debridement with special attention. Since bacteria remain in wounds after mechanical debridement, it cannot replace antimicrobial therapy strategies, but offer a complementary strategy to improve wound care. Thus, it could be shown that simple mechanical debridement is effective in reducing bacterial load and should be integrated into a therapeutic approach to wounds whenever appropriate.

Amplified gut feelings under inflammation and depressed mood: A randomized fMRI trial on interoceptive pain in healthy volunteers.

BACKGROUND: Inflammation and depressed mood constitute clinically relevant vulnerability factors for enhanced interoceptive sensitivity and chronic visceral pain, but their putative interaction remains untested in human mechanistic studies. We tested interaction effects of acute systemic inflammation and sad mood on the expectation and experience of visceral pain by combining experimental endotoxemia with a mood induction paradigm. METHODS: The double-blind, placebo-controlled, balanced crossover fMRI-trial in N = 39 healthy male and female volunteers involved 2 study days with either intravenous administration of low-dose lipopolysaccharide (LPS, 0.4 ng/kg body weight; inflammation condition) or saline (placebo condition). On each study, day two scanning sessions were conducted in an experimentally induced negative (i.e., sad) and in a neutral mood state, accomplished in balanced order. As a model of visceral pain, rectal distensions were implemented, which were initially calibrated to be moderately painful. In all sessions, an identical series of visceral pain stimuli was accomplished, signaled by predictive visual conditioning cues to assess pain anticipation. We assessed neural activation during the expectation and experience of visceral pain, along with unpleasantness ratings in a condition combining an inflammatory state with sad mood and in control conditions. All statistical analyses were accomplished using sex as covariate. RESULTS: LPS administration led to an acute systemic inflammatory response (inflammation X time interaction effects for TNF-α, IL-6, and sickness symptoms, all p <.001). The mood paradigm effectively induced distinct mood states (mood X time interaction, p <.001), with greater sadness in the negative mood conditions (both p <.001) but no difference between LPS and saline conditions. Significant main and interaction effects of inflammation and negative mood were observed for pain unpleasantness (all p <.05). During cued pain anticipation, a significant inflammation X mood interaction emerged for activation of the bilateral caudate nucleus and right hippocampus (all pFWE < 0.05). Main effects of both inflammation and mood were observed in multiple regions, including insula, midcingulate cortex, prefrontal gyri, and hippocampus for inflammation, and midcingulate, caudate, and thalamus for mood (all pFWE < 0.05). CONCLUSIONS: Results support an interplay of inflammation and sad mood on striatal and hippocampal circuitry engaged during visceral pain anticipation as well as on pain experience. This may reflect a nocebo mechanism, which may contribute to altered perception and interpretation of bodily signals. At the interface of affective neuroscience and the gut-brain axis, concurrent inflammation and negative mood may be vulnerability factors for chronic visceral pain.

How Can Experimental Endotoxemia Contribute to Our Understanding of Pain? A Narrative Review.

The immune system and the central nervous system exchange information continuously. This communication is a prerequisite for adaptive responses to physiological and psychological stressors. While the implicate relationship between inflammation and pain is increasingly recognized in clinical cohorts, the underlying mechanisms and the possibilities for pharmacological and psychological approaches aimed at neuro-immune communication in pain are not fully understood yet. This calls for preclinical models which build a bridge from clinical research to laboratory research. Experimental models of systemic inflammation (experimental endotoxemia) in humans have been increasingly recognized as an approach to study the direct and causal effects of inflammation on pain perception. This narrative review provides an overview of what experimental endotoxemia studies on pain have been able to clarify so far. We report that experimental endotoxemia results in a reproducible increase in pain sensitivity, particularly for pressure and visceral pain (deep pain), which is reflected in responses of brain areas involved in pain processing. Increased levels of blood inflammatory cytokines are required for this effect, but cytokine levels do not always predict pain intensity. We address sex-dependent differences in immunological responses to endotoxin and discuss why these differences do not necessarily translate to differences in behavioral measures. We summarize psychological and cognitive factors that may moderate pain sensitization driven by immune activation. Together, studying the immune-driven changes in pain during endotoxemia offers a deeper mechanistic understanding of the role of inflammation in chronic pain. Experimental endotoxemia models can specifically help to tease out inflammatory mechanisms underlying individual differences, vulnerabilities, and comorbid psychological problems in pain syndromes. The model offers the opportunity to test the efficacy of interventions, increasing their translational applicability for personalized medical approaches.

Endotoxin-Induced Physiological and Psychological Sickness Responses in Healthy Humans: Insights into the Post-Acute Phase.

INTRODUCTION: Experimental endotoxemia is a translational model of systemic inflammation that has contributed significantly to our current understanding of sickness behavior and inflammation-associated depression. Previous studies using this model revealed a strong association between cytokine levels, endocrine changes, and psychological sickness symptoms during the acute phase of inflammation. The objective of this randomized, double-blind, placebo-controlled crossover study was to gain insight into potential post-acute physiological and psychological consequences of endotoxin administration that may either persist or newly emerge between 24 and 72 h after injection. The main focus was on associations between serum levels of C-reactive protein (CRP) and affective symptoms as well as alterations in diurnal cortisol profile, the two key features of inflammation-associated depression. METHODS: Healthy male volunteers (N = 18) received an injection of either endotoxin (0.8 ng/kg) or placebo on two separate but otherwise identical study days, 7 days apart. Blood and saliva samples were collected during acute and post-acute phases after injection to measure blood inflammatory markers (interleukin [IL]-6, IL-1 receptor antagonist [ra], CRP) and salivary cortisol levels. In addition, participants completed a comprehensive battery of questionnaires to assess physical and psychological sickness symptoms. RESULTS: Endotoxin treatment induced a short-time rise in plasma IL-6 and a longer increase in IL-1ra. The increase in serum CRP was delayed compared to cytokines, peaking at 24 h and gradually decreasing until 72 h after injection. The inflammatory response was accompanied by bodily and psychological sickness symptoms which occurred only in the acute phase, whereas none of the symptoms persisted or recurred in the post-acute phase. Salivary cortisol levels were significantly increased during the acute phase and exhibited pronounced circadian changes. However, no significant differences in diurnal cortisol profiles were observed between placebo and endotoxin conditions on the days after treatment. CONCLUSION: Our findings suggest that CRP, which is elevated in patients with inflammation-associated depression, does not appear to be responsible for depressive symptomatology. Moreover, a single inflammatory episode is not sufficient to alter diurnal cortisol profiles, as observed in inflammation-associated depression. In addition, the absence of persistent lipopolysaccharide-induced psychological and physiological changes beyond the acute phase further supports the safety of endotoxin administration in humans.

The influence of psychological traits and prior experience on treatment expectations.

BACKGROUND: Placebo and nocebo responses are modulated by the treatment expectations of participants and patients. However, interindividual differences predicting treatment expectations and placebo responses are unclear. In this large-scale pooled analysis, we aim to investigate the influence of psychological traits and prior experiences on treatment expectations. METHODS: This paper analyses data from six different placebo studies (total n = 748). In all studies, participants' sociodemographic information, treatment expectations and prior treatment experiences and traits relating to stress, somatization, depression and anxiety, the Big Five and behavioral inhibition and approach tendencies were assessed using the same established questionnaires. Correlation coefficients and structural equation models were calculated to investigate the relationship between trait variables and expectations. RESULTS: We found small positive correlations between side effect expectations and improvement expectations (r = 0.187), perceived stress (r = 0.154), somatization (r = 0.115), agitation (r = 0.108), anhedonia (r = 0.118), and dysthymia (r = 0.118). In the structural equation model previous experiences emerged as the strongest predictors of improvement (ß = 0.32, p = .005), worsening (ß = -0.24, p = .005) and side effect expectations (ß = 0.47, p = .005). Traits related to positive affect (ß = - 0.09; p = .007) and negative affect (ß = 0.04; p = .014) were associated with side effect expectations. DISCUSSION: This study is the first large analysis to investigate the relationship between traits, prior experiences and treatment expectations. Exploratory analyses indicate that experiences of symptom improvement are associated with improvement and worsening expectations, while previous negative experiences are only related to side effect expectations. Additionally, a proneness to experience negative affect may be a predictor for side effect expectation and thus mediate the occurrence of nocebo responses.

How familiar are German dermatologists with placebo and nocebo effects and to what extent are these targeted in clinical practice: A survey within the dermatological community.

BACKGROUND: Every medical treatment inevitably comprises not only physiological, but also psychological components, reflected by placebo and nocebo effects, which significantly affect treatment outcome. However, the extent of knowledge on the mechanisms steering placebo and nocebo effects in the dermatological community in Germany is currently unclear. OBJECTIVES: To assess the state of knowledge about placebo and nocebo effects in the German dermatological community, to evaluate whether this knowledge is already being used in clinical practice, and to investigate whether German dermatologists are interested in learning more about the topic. METHODS: German Dermatologists, the majority working in their own practice, were asked to fill in an online survey addressing the knowledge about placebo and nocebo effects and the feasibility of special techniques to enhance placebo and minimize nocebo effects within the clinical routine. RESULTS: N = 154 complete (79%) or partial (21%) responses to the survey were recorded in the online database and included in the analysis. All participants reported to know what the placebo effect is and 59.7% (74/124) indicated that they already had experience with prescribing or recommending a treatment without active substances. In contrast, only 62.0% (80/129) stated to know what the nocebo effect is. Participants showed a rather superficial knowledge regarding placebo and nocebo mechanisms. The majority of participants (76.7%, 99/129) expressed their willingness to be further educated about the underlying mechanisms mediating placebo and nocebo effects and the possible application in clinical practice. CONCLUSIONS: The current survey offers a so far unique insight into the state of knowledge of German dermatologists on placebo and nocebo effects. The results indicate a need for education about this topic. Encouragingly, however, German dermatologists considered communication strategies to maximize placebo and reduce nocebo effects and expressed motivation to be trained to implement these strategies in everyday clinical practice.

Anterior insula morphology and vulnerability to psychopathology-related symptoms in response to acute inflammation.

INTRODUCTION: The role of inflammation in common psychiatric diseases is now well acknowledged. However, the factors and mechanisms underlying inter-individual variability in the vulnerability to develop psychopathology-related symptoms in response to inflammation are not well characterized. Herein, we aimed at investigating morphological brain regions central for interoception and emotion regulation, and if these are associated with acute inflammation-induced sickness and anxiety responses. METHODS: Systemic inflammation was induced using an intravenous injection of lipopolysaccharide (LPS) at a dose of 0.6 ng/kg body weight in 28 healthy individuals, while 21 individuals received an injection of saline (placebo). Individuals' gray matter volume was investigated by automated voxel-based morphometry technique on T1-weighted anatomical images derived from magnetic resonance imaging (MRI). Plasma concentrations of TNF-α and IL-6, sickness symptoms (SicknessQ), and state anxiety (STAI-S) were measured before and after the injection. RESULTS: A stronger sickness response to LPS was significantly associated with a larger anterior insula gray matter volume, independently from increases in cytokine concentrations, age, sex and body mass index (R2 = 65.6%). Similarly, a greater LPS-induced state anxiety response was related to a larger anterior insula gray matter volume, and also by a stronger increase in plasma TNF-α concentrations (R2 = 40.4%). DISCUSSION: Anterior insula morphology appears central in the sensitivity to develop symptoms of sickness and anxiety in response to inflammation, and could thus be one risk factor in inflammation-related psychopathologies. Because of the limited sample size, the current results need to be replicated.

Sick for science: experimental endotoxemia as a translational tool to develop and test new therapies for inflammation-associated depression.

Depression is one of the global leading causes of disability, but treatments remain limited and classical antidepressants were found to be ineffective in a substantial proportion of patients. Thus, novel effective therapies for the treatment of depression are urgently needed. Given the emerging role of inflammation in the etiology and pathophysiology of affective disorders, we herein illustrate how experimental endotoxemia, a translational model of systemic inflammation, could be used as a tool to develop and test new therapeutic options against depression. Our concept is based on the striking overlap of inflammatory, neural, and affective characteristics in patients with inflammation-associated depression and in endotoxin-challenged healthy subjects. Experimental administration of endotoxin in healthy volunteers is safe, well-tolerated, and without known long-term health risks. It offers a highly standardized translational approach to characterize potential targets of therapies against inflammation-associated depression, as well as to identify characteristics of patients that would benefit from these interventions, and, therefore, could contribute to improve personalization of treatment and to increase the overall rate of responders.

Can positive expectations help to improve the learning of risk literacy? A cluster-randomized study in undergraduate medical students.

BACKGROUND: Risk literacy, i.e., the ability to calculate and apply risk parameters, represents a key competence for risk communication and medical decision making. However, risk literacy is reportedly low in medical students. The successful acquisition of statistical competencies is often difficult, and can be hampered by emotional learning obstacles, calling for interventions to support learning. In this cluster-randomized study, we aimed to translate findings from placebo research to medical education. Specifically, we tested if the acquisition of risk literacy during a seminar unit can be facilitated by positive expectations, induced by a positive and non-threatening framing of the content and learning goals. METHODS: The study took place during a mandatory 2.5-h seminar on "risk literacy" for 2nd year medical students. The seminar teaches both statistical knowledge and its application in patient communication. To test the effects of expectations on risk literacy acquisition, the (otherwise identical) seminar was framed either as "communication training" (positive framing condition) or "statistics seminar" (negative framing condition). All N = 200 students of the semester were invited to participate, and cluster-randomized to the positive or negative framing condition (4 seminar groups each condition). Risk literacy was assessed with the "Quick Risk Test" (QRT) at the beginning and end of the seminar, along with statistics anxiety and subjective learning success using questionnaires. RESULTS: Data from N = 192 students were included. At the end of the seminar, risk literacy was increased in both framing conditions, with a significantly greater increase in QRT scores in the positive framing condition. Statistics anxiety was significantly decreased in both framing conditions, with no evidence of group differences. Subjective learning success was overall high and comparable between groups. CONCLUSIONS: Supporting our hypothesis, positive framing led to a significantly greater increase in risk literacy (i.e., in QRT scores). Our data offer first support that positive framing of learning goals may help to facilitate the acquisition of statistical knowledge. Expectation-orientated interventions may thus offer a feasible tool to optimize learning settings and framing of learning objectives in medical statistics courses.

[Systemic inflammation, "sickness behavior" and expectations : What role do expectations play in inflammation-associated symptoms?] / Systemische Entzündung, "Sickness Behavior" und Erwartungsprozesse : Welche Rolle spielen Erwartungen bei entzündungsassoziierten Symptomen?

BACKGROUND: Systemic inflammation is accompanied by unspecific physical and psychological symptoms of sickness, including pain and affective symptoms. These symptoms (commonly called "sickness behavior") are mediated by the central nervous effects of immune messengers such as pro-inflammatory cytokines. While adaptive during acute inflammation, sickness symptoms can have detrimental effects on quality of life during chronic inflammation and may contribute to comorbidity in chronic pain conditions. Despite the high clinical relevance of sickness behavior, psychological interventions aiming to modulate sickness symptoms have hardly been investigated. One approach could be the use of expectation effects, since positive and negative expectations (placebo or nocebo effects) have been shown to have an influence on pain and affect-related symptoms. OBJECTIVES: Herein, we summarize immunological and psychobiological factors that contribute to pain in the context of sickness behavior, with a major focus on findings from experimental endotoxemia. Against this background, we discuss how expectations could help to improve immune-mediated sickness symptoms and outline potential psychological and psychobiological mechanisms underlying this putative effect.

Learned immunosuppressive placebo responses in renal transplant patients.

Patients after organ transplantation or with chronic, inflammatory autoimmune diseases require lifelong treatment with immunosuppressive drugs, which have toxic adverse effects. Recent insight into the neurobiology of placebo responses shows that associative conditioning procedures can be employed as placebo-induced dose reduction strategies in an immunopharmacological regimen. However, it is unclear whether learned immune responses can be produced in patient populations already receiving an immunosuppressive regimen. Thus, 30 renal transplant patients underwent a taste-immune conditioning paradigm, in which immunosuppressive drugs (unconditioned stimulus) were paired with a gustatory stimulus [conditioned stimulus (CS)] during the learning phase. During evocation phase, after patients were reexposed to the CS, T cell proliferative capacity was significantly reduced in comparison with the baseline kinetics of T cell functions under routine drug intake (ƞp2 = 0.34). These data demonstrate, proof-of-concept, that learned immunosuppressive placebo responses can be used as a supportive, placebo-based, dose-reduction strategy to improve treatment efficacy in an ongoing immunopharmacological regimen.

Association of wound genesis on varying aspects of health-related quality of life in patients with different types of chronic wounds: Results of a cross-sectional multicentre study.

Patients with chronic wounds are significantly impaired in their health-related quality of life (HRQoL). The validated Wound-QoL questionnaire allows assessing the impact of chronic wounds on different aspects of HRQoL including physical, psychological, and everyday life-related impairments. The aim of our study was to investigate associations of these HRQoL dimensions with age, sex, and particularly wound genesis. In this retrospective, cross-sectional, multicentre study, Wound-QoL questionnaires from clinical routine of patients with venous leg ulcers, arterial leg ulcers, mixed leg ulcers, and diabetic foot ulcers (DFU) were evaluated. Effects of wound genesis, sex, and age were assessed with analysis of variance as well as correlation and multiple linear regression analyses. The completed questionnaires of 381 patients (f = 152/m = 229; mean age 68.9) were included. The wound genesis groups showed significantly different distributions of age and sex. We also found significant differences between those groups in everyday life-related QoL, with the greatest impairments in patients with DFU. Physical QoL scores showed significant differences between men and women depending on diagnosis group: in patients with venous leg ulcers, women had greater impairment of physical QoL than men. Independent of the underlying diagnosis, women had significantly higher scores in the psychological subscale as well as in the Wound-QoL sum scale. Within the subgroup of arterial leg ulcer patients, overall HRQoL sum score was significantly worse in older patients. Regression analyses supported negative effects of DFU diagnosis and female sex on HRQoL. Our data offer evidence that HRQoL shows clinically relevant differences between patients with chronic wounds of different genesis. Moreover, our data revealed that HRQoL is associated with age and sex, which should be considered when treating the patient groups. In order to be able to capture these important aspects and to offer individualised and patient-oriented treatments, the Wound-QoL should be implemented as a quick and uncomplicated standard instrument in daily routine. Patients with chronic wounds are significantly impaired in their health-related quality of life. Validated Wound-QoL questionnaire is a quick and easy-to-use instrument for daily practice. Wound-related quality of life shows clinically relevant differences between patients with chronic wounds of different genesis. Wound-related quality of life is associated with age and sex, which should be considered when treating these patient groups. Health-related quality of life should be regularly objectified in all patients with chronic wounds with a validated measuring instrument.

Elucidating vulnerability to inflammation-induced hyperalgesia: Predictors of increased musculoskeletal pain sensitivity during experimental endotoxemia.

Despite broad clinical implications, the mechanisms linking inflammation and pain remain incompletely understood. Using human experimental endotoxemia as a translational model of systemic inflammation, we aimed to elucidate putative vulnerability factors of inflammation-induced musculoskeletal hyperalgesia. We pooled data from three published randomized controlled trials, resulting in a sample of N = 98 healthy volunteers who received either low-dose endotoxin (lipopolysaccharide) or vehicle (saline) intravenously. As measure of musculoskeletal pain sensitivity, pressure pain thresholds (PPTs) were assessed at baseline and 3 h post injection with a handheld algometer for the low back (erector spinae muscle), calf (gastrocnemius muscle), and shoulder region (deltoid muscle). Implementing multiple regression models, we tested the contribution of putative vulnerability factors on musculoskeletal hyperalgesia during systemic inflammation, including acute changes in pro-inflammatory cytokines, state anxiety and mood, as well as pre-existing symptoms of anxiety and depression. Endotoxin application led to significant increases in plasma cytokines, state anxiety, and negative mood, and significantly decreased PPTs for all muscle groups. Regression models revealed that greater M. erector spinae PPT changes were predicted by higher HADS-anxiety scores. Higher TNF-α concentration emerged as predictor for M. gastrocnemius PPT changes, and more pronounced TNF-α increase and higher HADS-anxiety were predictive for M. deltoideus PPTs. HADS scores emerged as predictor for a mean PPT score (computed across all body sites). Together, our results indicate that musculoskeletal hyperalgesia during systemic inflammation is related to pro-inflammatory cytokines, specifically TNF-α. Importantly, subclinical anxiety symptoms (even though in a low and normal range in this cohort of healthy volunteers) may contribute to inflammation-induced hyperalgesia, making individuals more vulnerable to the detrimental effects of systemic inflammation.

Impact of acute inflammation on the extinction of aversive gut memories.

Impaired extinction of pain-related fear memories can lead to persistent or resurging fear of pain, contributing to the development and maintenance of chronic pain conditions. The mechanisms underlying maladaptive pain-related learning and memory processes remain incompletely understood, particularly in the context of interoceptive, visceral pain. Inflammation is known to interfere with learning and memory, but its effects on the extinction of pain-related fear memories have never been tested. In a randomized, double-blind, placebo-controlled study, we assessed the impact of experimental acute inflammation on the extinction and reinstatement of conditioned visceral pain-related fear. Forty healthy male volunteers underwent differential fear conditioning with visceral pain as clinically relevant unconditioned stimulus (US). Participants then received an intravenous injection of either 0.8 ng/kg lipopolysaccharide (LPS) as inflammatory stimulus or physiological saline as placebo, and extinction training was conducted at the peak of the inflammatory response. Extinction recall and reinstatement test were performed after overnight consolidation. Results showed that visceral pain represents an effective US, eliciting pronounced conditioned pain-related fear responses. Repeated unreinforced presentation of the pain-predictive cue during extinction training resulted in full extinction of the conditioned behavioral response. However, unexpected re-exposure to the US during reinstatement test resulted in return of fear. Despite pronounced LPS-induced effects on inflammatory markers, cortisol, and negative affect, we did not find evidence that acute inflammation resulted in altered fear extinction. The findings support the notion that visceral pain-related fear learning establishes a robust aversive memory trace that remains preserved during inhibitory learning, leaving a latent vulnerability for the return of fear. Inflammation during inhibitory learning did neither weaken nor further amplify this aversive memory trace, suggesting that it is rather resistant to acute inflammation-induced effects, at least in healthy individuals with no additional vulnerability factors.

Fatigue and sleepiness responses to experimental inflammation and exploratory analysis of the effect of baseline inflammation in healthy humans.

Inflammation is believed to be a central mechanism in the pathophysiology of fatigue. While it is likely that dynamic of the fatigue response after an immune challenge relates to the corresponding cytokine release, this lacks evidence. Although both fatigue and sleepiness are strong signals to rest, they constitute distinct symptoms which are not necessarily associated, and sleepiness in relation to inflammation has been rarely investigated. Here, we have assessed the effect of an experimental immune challenge (administration of lipopolysaccharide, LPS) on the development of both fatigue and sleepiness, and the associations between increases in cytokine concentrations, fatigue and sleepiness, in healthy volunteers. In addition, because chronic-low grade inflammation may represent a risk factor for fatigue, we tested whether higher baseline levels of inflammation result in a more pronounced development of cytokine-induced fatigue and sleepiness. Data from four experimental studies was combined, giving a total of 120 subjects (LPS N = 79, 18 (23%) women; Placebo N = 69, 12 (17%) women). Administration of LPS resulted in a stronger increase in fatigue and sleepiness compared to the placebo condition, and the development of both fatigue and sleepiness closely paralleled the cytokine responses. Individuals with stronger increases in cytokine concentrations after LPS administration also suffered more from fatigue and sleepiness (N = 75), independent of gender. However, there was no support for the hypothesis that higher baseline inflammatory markers moderated the responses in fatigue or sleepiness after an inflammatory challenge. The results demonstrate a tight connection between the acute inflammatory response and development of both fatigue and sleepiness, and motivates further investigation of the involvement of inflammation in the pathophysiology of central fatigue.

Immunological and behavioral responses to in vivo lipopolysaccharide administration in young and healthy obese and normal-weight humans.

Obesity is associated with an increase prevalence of neuropsychiatric symptoms and diseases, such as depression. Based on the facts that pro-inflammatory cytokines are able to modulate behavior, and that obesity is characterized by a chronic low-grade inflammatory state, inflammation has been hypothesized to contribute to the neuropsychiatric comorbidity in obese individuals. However, a causal link between inflammation and the development of neuropsychiatric symptoms is hard to establish in humans. Here, we used an inflammatory stimulus, i.e. the intravenous injection of lipopolysaccharide (LPS), in a double-blind placebo-controlled design, to determine the vulnerability of obese individuals to inflammation-induced behavioral changes. The hypothesis was that obese individuals would show heightened behavioral response compared to normal-weight subjects for the same inflammatory stimulus, reflecting an increased sensitivity to the behavioral effects of pro-inflammatory cytokines. LPS (dose 0.8 ng/kg body weight, adjusted for estimated blood volume in obese subjects) and placebo (saline) were intravenously injected in 14 obese healthy subjects and 23 normal-weight healthy subjects in a within-subject, randomized, crossover design. LPS administration induced, in both groups, an acute increase in blood concentrations of cytokines (interleukin-6, tumor necrosis factor-α, and IL-10), as well as in body temperature, cortisol, norepinephrine, sickness symptoms, fatigue, negative mood, and state anxiety. There were little differences in the immune and behavioral responses to LPS between obese and normal-weight subjects, but the cortisol response to LPS was strongly attenuated in obese individuals. Higher percentage of body fat was related to a lower cortisol response to LPS. Taken together, the population of young and healthy obese individuals in this study did not exhibit an increased behavioral sensitivity to cytokines, but an attenuated cortisol response to the immune challenge. Future studies will need to determine whether additional physiological and psychological factors interact with the state of obesity to increase the risk for inflammation-induced neuropsychiatric symptoms.

Pilot study on the influence of cold atmospheric plasma on bacterial contamination and healing tendency of chronic wounds.

BACKGROUND: Cold atmospheric plasma (CAP) has been used successfully for wound treatment, with thrice weekly treatment intervals. In this study, we wished to investigate whether comparably beneficial results can be achieved even with once weekly CAP treatment. PATIENTS AND METHODS: In this randomized clinical pilot study (RCT) patients with therapy-refractory chronic wounds were examined over a maximum of twelve weeks. Groups 1 and 2 were treated with CAP once and twice a week, respectively. Patients in Group 3 received placebo therapy once a week. RESULTS: Wound area decreased significantly by 63.0 % in Group 1 (n = 14, P = 0.005) and by 46.8 % in Group 2 (n = 13, P = 0.007). In Group 3 (n = 10) the wounds grew on average 17.5 % larger. A significant reduction in pain was measured in both CAP-treated groups (Group 1: P = 0.042; Group 2: P = 0.027). Only in Group 2 was there a significant improvement in wound-specific quality of life (P = 0.005). After the 12-week CAP treatment, the reduction in bacterial load compared to the day of study inclusion averaged 50.4 % for Group 1 and 35.0 % for Group 2. CONCLUSIONS: Our RCT shows that treatment with CAP improves various aspects of wound healing in patients with therapy-refractory chronic wounds. The results obtained for once weekly treatment with CAP were not inferior to those obtained when CAP treatment was three times a week. Treatment once a week is also easier and more economical to implement in clinical routine.

Influence of placebo effects on quality of life and wound healing in patients with chronic venous leg ulcers.

INTRODUCTION: Placebo effects are used in the treatment of various medical conditions. To date, there is little scientific data in this regard as it relates to skin diseases in general and hardly any data with respect to wound healing in particular. MATERIAL AND METHODS: In a prospective randomized controlled trial, patients with chronic venous leg ulcers were observed for a period of 14 weeks. The objective was to investigate whether raising patients' expectations with regard to a novel wound treatment might have an effect on wound healing processes as well as wound-related quality of life, anxiety, depression and pain. RESULTS: Overall, 20 patients were included in the trial. They were stratified based on gender and randomized to either the intervention (IG) or the control group (CG). In both groups, the wound area decreased significantly over the course of the observation period. Unlike patients in the CG, those in the IG experienced significant improvement in wound-related quality of life (wound-QoL) in terms of both the overall score and the various subscales. Neither group showed significant changes with respect to pain, anxiety and depression. CONCLUSIONS: Our study is the first to show that - merely by raising patients' expectations for a novel treatment - placebo effects can significantly improve quality of life in patients with chronic venous leg ulcers. In the future, our findings should be integrated into the development of treatment concepts for patients with chronic wounds and should be investigated in larger cohorts.

Prospective clinical study on the efficacy of bacterial removal with mechanical debridement in and around chronic leg ulcers assessed with fluorescence imaging.

Bacterial colonisation in wounds delays healing, mandating regular bacterial removal through cleaning and debridement. Real-time monitoring of the efficacy of mechanical debridement has recently become possible through fluorescence imaging. Red fluorescence, endogenously produced during bacterial metabolism, indicates regions contaminated with live bacteria (>104 CFU/g). In this prospective study, conventional and fluorescence photos were taken of 25 venous leg ulcers before and after mechanical debridement, without use of antiseptics. Images were digitally segmented into wound bed and the periwound regions (up to 1.5 cm outside bed) and pixel intensity of red fluorescence evaluated to compute bacterial area. Pre-debridement, bacterial fluorescence comprised 10.4% of wound beds and larger percentages of the periwound area (~25%). Average bacterial reduction observed in the wound bed after a single mechanical debridement was 99.4% (p<0.001), yet periwound bacterial reduction was only 64.3%. On average, across bed and periwound, a single mechanical debridement left behind 29% of bacterial fluorescence positive tissue regions. Our results show the substantial effect that safe, inexpensive, mechanical debridement can have on bacterial load of venous ulcers without antiseptic use. Fluorescence imaging can localise bacterial colonised areas and showed persistent periwound bacteria post-debridement. Fluorescence-targeted debridement can be used quickly and easily in daily practice.

[Where did all the men in child and adolescent psychiatry and psychotherapy go? The influence of gender on the choice of specialization]. / Wo sind die Männer im Fachgebiet Kinder- und Jugendpsychiatrie und Psychotherapie?

Where did all the men in child and adolescent psychiatry and psychotherapy go? The influence of gender on the choice of specialization Abstract. Objective: To examine the factors influencing graduates to choose child and adolescent psychiatry (CAP) or orthopaedic surgery (OR) as a career specialty. Method: We distributed a web-based survey to residents in child and adolescent psychiatry and orthopedic surgery in Germany. The survey included questions related to the factors contributing to their career choice, particularly sociodemographic, workplace, and education-related matters. Results: 101 participants completed the questionnaires (CAP: 49 women, 10 men; OR 21 women and 21 men). CAP residents were significantly older and more often married with children. Exposure to the subject during medical school was significantly more common among OR residents. CAP residents rated the factors "time for breaks," "regular work hours," "structured workday," "reconciliation of work and family life," "overall work load," and "sufficient time for each individual patient" as significantly more important than did OR residents. OR residents in turn considered "spectacular cases," "fast decision-making," "high technical requirements," and "positive experiences during medical school" as significantly more important. A family-friendly workplace was especially more important to woman in CAP. Conclusions: There is a need to rebrand the perception of psychiatry and to expose medical students early on to the subject if we are to attract more (male) psychiatrists in the future.