Assessment of a novel smartglass-based point-of-care fusion approach for mixed reality-assisted targeted prostate biopsy: A pilot proof-of-concept study.

Purpose: While several biopsy techniques and platforms for magnetic resonance imaging (MRI)-guided targeted biopsy of the prostate have been established, none of them has proven definite superiority. Augmented and virtual reality (mixed reality) smartglasses have emerged as an innovative technology to support image-guidance and optimize accuracy during medical interventions. We aimed to investigate the benefits of smartglasses for MRI-guided mixed reality-assisted cognitive targeted biopsy of the prostate. Methods: For prospectively collected patients with suspect prostate PIRADS lesions, multiparametric MRI was uploaded to a smartglass (Microsoft® Hololens I), and smartglass-assisted targeted biopsy (SMART TB) of the prostate was executed by generation of a cognitive fusion technology at the point-of-care. Detection rates of prostate cancer (PCA) were compared between SMART TB and 12-core systematic biopsy. Assessment of SMART-TB was executed by the two performing surgeons based on 10 domains on a 10-point scale ranging from bad (1) to excellent (10). Results: SMART TB and systematic biopsy of the prostate were performed for 10 patients with a total of 17 suspect PIRADS lesions (PIRADS 3, n = 6; PIRADS 4, n = 6; PIRADS 5, n = 5). PCA detection rate per core was significant (p < 0.05) higher for SMART TB (47%) than for systematic biopsy (19%). Likelihood for PCA according to each core of a PIRADS lesion (17%, PIRADS 3; 58%, PIRADS 4; 67%, PIRADS 5) demonstrated convenient accuracy. Feasibility scores for SMART TB were high for practicality (10), multitasking (10), execution speed (9), comfort (8), improvement of surgery (8) and image quality (8), medium for physical stress (6) and device handling (6) and low for device weight (5) and battery autonomy (4). Conclusion: SMART TB has the potential to increase accuracy for PCA detection and might enhance cognitive MRI-guided targeted prostate biopsy in the future.

[Virtual and augmented reality in urology]. / Virtual und Augmented Reality in der Urologie.

Although continuous technological developments have optimized and evolved medical care throughout time, these technologies were mostly still comprehensible for users. Driven by immense financial efforts, modern innovative products and technical solutions are transforming medicine today and will do so even more in the future: virtual and augmented reality. This review critically summarizes the current literature and future uses of virtual and augmented reality in the field of urology.

The PT2D-Score: a novel tool to predict complications and economic outcome after radical cystectomy.

BACKGROUND: Radical cystectomy (RC) has a high morbidity and leads to a significant socio-economic burden. We aimed to investigate pre-, intra-, and post-operative variables to create a novel score predicting both post-operative clinical (complications) and economic (length of hospital stay) outcome after RC. METHODS: We retrospectively evaluated clinical and histopathological data of 317 patients after RC. We performed univariate and multivariate logistic regression analyses to identify variables associated with post-operative clinical (30-day morbidity according to Clavien-Dindo complications) and economic (length of hospital stay) outcome. RESULTS: In multivariate analysis, a high number of intraoperative transfusions (T) of packed red blood cells predicted major complications (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.10-2.58, p = 0.017), preoperative potassium (P) level predicted three or more complications (OR for high preoperative potassium 0.71, 95% CI 0.52-0.98, p = 0.037), and high drain (D) loss on post-operative day 1 predicted a longer hospital stay ≥ 22 days (OR 1.57, 95% CI 1.04-2.35, p = 0.003). The PT2D-Score was able to predict three or more complications (area under the curve: 0.70, 95% CI 0.61-0.78, p < 0.001) and a hospital stay of ≥ 22 days in patients after radical cystectomy (area under the curve: 0.63, 95% confidence interval 0.53-0.72, p = 0.012). CONCLUSIONS: The novel PT2D-Score combines preoperative potassium level, intraoperative blood transfusion, and post-operative drain loss to predict both clinical (30-day morbidity) and economic (length of hospital stay) outcome for patients undergoing RC. After validation in a larger cohort, the novel PT2D-Score might serve as an additional criterion to identify patients for intensified monitoring after RC.

Glucocorticoid and inflammatory reactivity to a repeated physiological stressor in insomnia disorder.

Despite known associations of insomnia disorder with alterations in cytokine and glucocorticoid (GC) production, neither the sensitivity of immune cells to a GC signal nor the reactivity of the hypothalamus-pituitary-adrenal (HPA) axis and inflammatory system to stress, or adaptation of these systems to repeated stress have been assessed in patients with insomnia. To investigate potential dysregulation in stress reactivity and adaptation to repeated exposure, a physiological stressor (the cold pressor test; CPT) was repeatedly administered to N = 20 participants with insomnia disorder (based on DSM-V, 18 females, age 30 ±â€¯2.5 years) and N = 20 sex-matched healthy controls following an at-home actigraphy and in-laboratory PSG. HPA and inflammatory markers (serum cortisol, plasma interleukin [IL]-6) were measured at baseline/resting levels and following each of the three CPTs. In addition, sensitivity of monocytes to the synthetic GC dexamethasone was assessed in-vitro at baseline levels in order to examine the cortisol-IL-6 interplay at the cell level. Compared to healthy controls, individuals with insomnia disorder exhibited shorter sleep duration as assessed by actigraphy and PSG (p ≤ 0.05). HPA, but not inflammatory reactivity to the repeated CPT challenge was greater in insomnia disorder (p ≤ 0.05 for group effect), due to greater cortisol responses to the initial CPT (p ≤ 0.05). There were no between-group differences in the ability of the HPA to adapt to stress repetition nor in basal/resting levels of cortisol, IL-6, and GC sensitivity. These findings suggest that insomnia disorder potentiates HPA axis reactivity to initial/novel stressors, which may constitute a pathway underlying adverse health consequences in the long term.

[Computed tomography angiography as the basis for optimized therapy planning before endovascular aneurysm repair (EVAR)]. / CT-Angiographie als Grundlage der optimierten Therapieplanung vor endovaskulärer Aneurysmaausschaltung (EVAR).

Computed tomography angiography (CTA) of the aorta is an accepted standard diagnostic procedure for preoperative evaluation and planning of endovascular treatment of abdominal aortic aneurysms (endovascular aortic repair EVAR). The CTA method delivers all relevant anatomical and morphological information on the underlying pathology of the aorta and pelvic axes. Various software solutions are available for multiplanar reconstruction of the CT data for exact measurement of the access routes and landing zones and are essential components of individualized operation planning. The synthesis of all CT-based information allows a safe and exactly targeted release of the stent graft in the aorta. Furthermore, the periprocedural radiation dose can be reduced by a precise preoperative planning of the positions to be irradiated during implantation.

Pain sensitivity and modulation in primary insomnia.

Sleep of good quantity and quality is considered a biologically important resource necessary to maintain homeostasis of pain-regulatory processes. To assess the role of chronic sleep disturbances in pain processing, we conducted laboratory pain testing in subjects with primary insomnia. Seventeen participants with primary insomnia (mean ± SEM 22.6 ± 0.9 yrs, 11 women) were individually matched with 17 healthy participants. All participants wore an actigraph device over a 2-week period and completed daily sleep and pain diaries. Laboratory pain testing was conducted in a controlled environment and included (1) warmth detection threshold testing, (2) pain sensitivity testing (threshold detection for heat and pressure pain), and (3) tests to access pain modulatory mechanisms (pain facilitation and inhibition). Primary insomnia subjects reported experiencing spontaneous pain on twice as many days as healthy controls during the at-home recording phase (p < 0.05). During laboratory testing, primary insomnia subjects had lower pain thresholds than healthy controls (p < 0.05 for heat pain detection threshold, p < 0.08 for pressure pain detection threshold). Unexpectedly, pain facilitation, as assessed with temporal summation of pain responses, was reduced in primary insomnia compared to healthy controls (p < 0.05). Pain inhibition, as assessed with the diffuse noxious inhibitory control paradigm (DNIC), was attenuated in insomnia subjects when compared to controls (p < 0.05). Based on these findings, we propose that pain-inhibitory circuits in patients with insomnia are in a state of constant activation to compensate for ongoing subclinical pain. This constant activation ultimately may result in a ceiling effect of pain-inhibitory efforts, as indicated by the inability of the system to adequately function during challenge.

Low doses of dexamethasone affect immune parameters in the absence of immunological stimulation.

Recent findings suggest an important role of subtle changes in the plasma levels of inflammatory cytokines within the brain-immune interplay. It is unclear how such changes are regulated in the absence of acute inflammatory or infectious stimuli. Endocrine systems are a good candidate, because innate immunity and the hypothalamo-pituitary-adrenal (HPA)-system are closely related: glucocorticoids have immunosuppressive properties and modulate cytokine release from stimulated mononuclear blood cells in vitro and the immune response in vivo, but it still remains unclear, whether they also modulate circulating cytokine levels in the absence of immunological stimuli. We measured the influence of 1.5 or 3.0 mg dexamethasone (DEX) per os at 09:00 or 21:00 hours on body temperature, cortisol plasma levels, differential white blood cell counts, and cytokine plasma levels in 40 healthy male volunteers using a double-blind, placebo-controlled study design. In addition to significant morning-evening differences in tympanic temperature and several immune parameters, we found that DEX-intake significantly increased tympanic temperature, decreased cortisol plasma levels, altered differential white blood cell counts and induced changes in unstimulated plasma cytokine levels. Whereas the levels of TNF-alpha and sTNF-R p75 were reduced, the levels of sTNF-R p55 increased after a transient decrease.

[Airway management in pediatric anesthesia]. / Atemwegsmanagement in der Kinderanästhesie.

Airway management in newborns, infants, and children is a challenge to anesthesia practitioners due to the particular anatomic and physiological characteristics. The larynx is positioned more cephalad, the occiput is protuberant, and the neck is short, which makes a special position for anesthesia induction necessary. The high respiratory frequency due to high oxygen demand and carbon dioxide production has to be taken into consideration during manual as well as mechanical ventilation. Different devices are available for airway management. Simple mask ventilation can be improved by a Wendl tube. The classic laryngeal mask can be recommended as a safe airway device in many indications, specifically in children with an upper respiratory airway infection. If intubation is indicated, an optimal size and position of the endotracheal tube has to be provided. Fiberoptic endotracheal intubation is recommended if a difficult airway is known or anticipated due to a craniofacial syndrome.

Obsessive-compulsive disorder: a critical review of therapeutic perspectives.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a chronic disabling disease with profound implications for social functioning. Thirty per cent of all patients with OCD show insufficient improvement with state-of-the-art treatment. Conventional treatment and alternative treatment options for this population were investigated. METHOD: A selective review of the relevant scientific literature on OCD treatment and treatment resistance was conducted. RESULTS: In addition to serotonin reuptake inhibitors (SRIs) and cognitive-behavioural therapy, alternative monotherapies, SRI augmentation strategies with a variety of drugs and electroconvulsive therapy have shown results in individual cases, but no conclusive evidence has been found in placebo-controlled trials. While studies investigating neurosurgery for refractory OCD show positive results, most of these studies have methodological shortcomings. CONCLUSION: Novel approaches currently under investigation that have shown promising effects for treatment-resistant OCD include SRI augmentation with atypical antipsychotics and chronic deep brain stimulation, a new surgical technique. Placebo-controlled trials for both treatment options will be needed to confirm preliminary findings.

Engineering of carbon catabolite repression in recombinant xylose fermenting Saccharomyces cerevisiae.

Two xylose-fermenting glucose-derepressed Saccharomyces cerevisiae strains were constructed in order to investigate the influence of carbon catabolite repression on xylose metabolism. S. cerevisiae CPB.CR2 (Delta mig1, XYL1, XYL2, XKS1) and CPB.MBH2 (Delta mig1, Delta mig2, XYL1, XYL2, XKS1) were analysed for changes in xylose consumption rate and ethanol production rate during anaerobic batch and chemostat cultivations on a mixture of 20 g l(-1) glucose and 50 g l(-1) xylose, and their characteristics were compared to the parental strain S. cerevisiae TMB3001 ( XYL1, XYL2, XKS1). Improvement of xylose utilisation was limited during batch cultivations for the constructed strains compared to the parental strain. However, a 25% and 12% increased xylose consumption rate during chemostat cultivation was achieved for CPB.CR2 and CPB.MBH2, respectively. Furthermore, during chemostat cultivations of CPB.CR2, where the cells are assumed to grow under non-repressive conditions as they sense almost no glucose, invertase activity was lower during growth on xylose and glucose than on glucose only. The 3-fold reduction in invertase activity could only be attributed to the presence of xylose, suggesting that xylose is a repressive sugar for S. cerevisiae.

The endotoxin-induced increase of cytokines is followed by an increase of cortisol relative to dehydroepiandrosterone (DHEA) in healthy male subjects.

Dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEAS) inhibit T-helper lymphocyte type 2 immune reactions and exert anti-inflammatory effects in some chronic inflammatory diseases. Both DHEA and, in particular, DHEAS levels are dramatically decreased in chronic inflammatory diseases whereas cortisol levels remain stable or are elevated. However, the time course of cortisol relative to DHEA production is not known. We tested whether administration of endotoxin to healthy male subjects can induce an early predominance of cortisol relative to DHEA and DHEAS. It is demonstrated that endotoxin induces a dose-dependent increase of cortisol in relation to DHEA (no effect at 0.2 ng endotoxin/kg body weight (b.w.), clear effect at 0.4 and 0.8 ng/kg b.w., p<0.05) and DHEAS (tested at 0.4 ng/kg b.w., P=0.014). The increase of cortisol relative to DHEA appears 4 h after endotoxin injection and 2 h after a strong increase of interleukin (IL)-6 relative to tumour necrosis factor (TNF). In addition, an increase of cortisol relative to 17OH-progesterone was observed. The ratio of serum IL-6/TNF was positively correlated with the ratio of serum cortisol/DHEA (R(Rank)=0.472, P=0.041) and serum cortisol/17OH-progesterone (R(Rank)=0.514, P=0.048). In conclusion, dissociation of cortisol relative to DHEA, DHEAS or 17OH-progesterone appears very early during a systemic inflammatory response which is associated with an increase of IL-6 relative to TNF. As in chronic inflammatory diseases, during an acute inflammatory response with endotoxin, these physiological hormone changes are probably necessary to achieve adequate cortisol levels at the expense of adrenal androgens.

Endotoxin-induced changes in food consumption in healthy volunteers are associated with TNF-alpha and IL-6 secretion.

This study examined the effects of endotoxin administration on food and water consumption in humans, and the associations between these changes and endotoxin-induced secretion of cytokines, cortisol, and fever. Twenty healthy male volunteers received an i.v. injection of Salmonella abortus equi endotoxin (0.8 ng/kg) or saline in two experimental sessions. Blood samples were collected hourly, and rectal temperature was monitored continuously. Food consumption was significantly reduced at 0-4 h and significantly elevated at 4-5 h after the endotoxin injection. Endotoxin administration had no significant effect on water consumption. Endotoxin-induced secretion of TNF-alpha and IL-6 was positively associated with the decrease in food consumption (r=0.61 and 0.68), and negatively associated with the rebound increase in food consumption (r=-0.53 and -0.45). Neither the febrile response, nor the secretion of cortisol was associated with the changes in food consumption. These results suggest that TNF-alpha and IL-6 are involved in endotoxin-induced anorexia in humans.

Body weight, the tumor necrosis factor system, and leptin production during treatment with mirtazapine or venlafaxine.

Weight gain is a frequent and important side effect of psychopharmacotherapy. Recent studies suggest that the fat-cell-derived hormone leptin and the tumor necrosis factor-alpha (TNF-alpha) cytokine system are pathophysiologically involved. No information is available concerning the influence of the antidepressants mirtazapine and venlafaxine on these immunoendocrine variables. An open-labeled study was performed in 20 patients suffering from major depression treated with either mirtazapine (N = 11) or venlafaxine (N = 9). During 4 weeks, the patients' weight, body mass index (BMI), and plasma levels of leptin, TNF-alpha, sTNF-R p55, and sTNF-R p75 were assessed. Mirtazapine induced a significant increase in weight (mean weight gain: 2.4 kg) that was evident after the first week of treatment. In parallel, the plasma levels of TNF-alpha and both soluble TNF receptors increased. In addition, a slight rise in leptin levels, which occurred slowly and was significant only at the end of the 4 th week of treatment, was observed. Weight decreased slightly but significantly in patients treated with venlafaxine (mean weight loss: 0.4 kg), whereas plasma levels of leptin, TNF-alpha, or soluble TNF receptors did not change significantly. The present results further support the notion that the activation of the TNF-alpha cytokine system is an early, sensitive, and specific marker of weight gain induced by psychotropic agents. In contrast, the effects of such drugs on leptin production seem to be less sensitive with respect to weight gain and more variable.

[On the clinical relevance of clozapine-triggered release of cytokines and soluble cytokine-receptors]. / Zur klinischen Relevanz der Wirkung von Clozapin auf die Freisetzung von Zytokinen und löslichen Zytokinrezeptoren.

Cytokines are pivotal mediators of the interaction between immunocompetent cells. Moreover, they mediate the interaction between the immune system and other physiological systems, including the CNS. It has been shown recently that the antipsychotic drug clozapine stimulates in vivo the release of cytokines and soluble cytokine receptors. This holds true for the tumor necrosis factor(TNF)-system, the interleukin(IL)-2-system, IL-6, and granulocyte colony-stimulating factor (G-CSF). The present paper discusses the clinical relevance of these findings for the pathophysiology of clozapine-induced side-effects. It is very probable that TNF-alpha plays an important role in clozapin-induced fever and in the hematopoetic side effects, including agranulocytosis. Moreover, it is likely that TNF-alpha and other cytokines are involved in metabolic (weight gain, diabetes), cardiac (myocarditis), CNS (sedation) and other rare side effects. The mechanisms underlying clozapine-induced immunomodulation are unknown. Hence, further studies are very important to enhance our understanding of clozapins's side effects and to develop strategies for prevention and treatment.

Effects of sleep on endotoxin-induced host responses in healthy men.

OBJECTIVE: To examine whether increased sleep during viral or bacterial infections supports host defense mechanisms. METHODS: To test this assumption in humans, healthy male subjects were assigned either to sleep from 2300 to 0700 hours (n = 10) or to stay awake through the night (n = 10). In the sleeping subjects Salmonella abortus equi endotoxin (0.4 ng/kg) or placebo were intravenously injected in balanced order during the first SWS episode. The age-matched, sleep-deprived subjects were injected at the same time point. RESULTS: As expected, endotoxin significantly increased rectal temperature, the plasma levels of cortisol, tumor necrosis factor-alpha (TNF-alpha), the soluble TNF receptors p55 and p75, Interleukin (IL)-6, the IL-1 receptor antagonist (RA), leukocyte, and granulocyte counts in both sleeping and sleep-deprived subjects, whereas lymphocyte and monocyte counts were transiently reduced. Time courses of endotoxin-induced host responses did not differ between the sleep and sleep deprivation groups. Endotoxin did not affect the amount of nocturnal wakefulness, nonrapid-eye-movement (NREM) sleep, or rapid-eye-movement (REM) sleep across the total night compared with placebo, but significantly increased electroencephalogram-arousals (EEG-arousals) in stage 2 and decreased arousals in SWS. In addition, the amount of SWS, spectral EEG-delta and -theta power was increased at the beginning and at the end of the sleep period, respectively, when the degree of immune activation was relatively low. CONCLUSION: The present results support the notion that short-term sleep deprivation is unlikely to harm the immune system as far as unspecific acute responses are concerned. The effects of endotoxin on sleep in this case support prior observations that in humans, enhanced SWS and intensified NREM sleep occur when host defense activation is subtle.

Normal plasma levels of orexin A (hypocretin-1) in narcoleptic patients.

Deficient orexin signaling has been shown to cause narcolepsy-like conditions in animals. In human narcolepsy, CSF levels of orexin A (hypocretin-1) were reported to be low in most cases. The authors measured CSF and plasma orexin A levels in patients with narcolepsy and in controls. Confirming earlier studies, they found CSF orexin A levels to be extremely low in patients with narcolepsy. However, plasma orexin A levels did not differ from those observed in controls. These results suggest that orexin deficiency in patients with narcolepsy is a phenomena restricted to the CNS.

Low leptin levels but normal body mass indices in patients with depression or schizophrenia.

Appetite, food intake and weight are frequently altered in psychiatric disorders such as major depression and schizophrenia. The few studies investigating weight and the body mass index (BMI) have yielded variable results. Leptin, a fat cell-derived hormone signalling to the brain the size of the adipose tissue, plays a pivotal role in the regulation of weight and food intake. Moreover, leptin is involved in the control of other behaviors and in brain development. There is almost no information about the amounts of circulating leptin in major depression or schizophrenia. We investigated the BMI and plasma leptin levels in patients with major depression (n = 62), schizophrenia (n = 42), and in healthy controls (n = 64). Mean BMIs did not differ between groups. However, leptin levels were significantly lower in both patient groups compared to healthy controls. Moreover, patients suffering from schizophrenia showed significantly lower leptin levels than depressed patients. Decreased leptin levels were independent of psychotropic medication. We conclude that depression and schizophrenia go along with decreased systemic leptin concentrations that cannot be explained by medication or an altered BMI. Hence, leptin might play an important pathophysiological role in these psychiatric disorders that deserves further scientific attention.

Cytokine-associated emotional and cognitive disturbances in humans.

BACKGROUND: Infectious, autoimmune, and neurodegenerative diseases are associated with profound psychological disturbances. Studies in animals clearly demonstrate that cytokines mediate illness-associated behavioral changes. However, the mechanisms underlying the respective psychological alterations in humans have not been established yet. Therefore, we investigated the effects of low-dose endotoxemia, a well-established and safe model of host-defense activation, on emotional, cognitive, immunological, and endocrine parameters. METHODS: In a double-blind, crossover study, 20 healthy male volunteers completed psychological questionnaires and neuropsychological tests 1, 3, and 9 hours after intravenous injection of Salmonella abortus equi endotoxin (0.8 ng/kg) or saline in 2 experimental sessions. Blood samples were collected hourly, and rectal temperature and heart rate were monitored continuously. RESULTS: Endotoxin had no effects on physical sickness symptoms, blood pressure, or heart rate. Endotoxin caused a mild increase in rectal temperature (0.5 degrees C), and increased the circulating levels of tumor necrosis factor alpha (TNF-alpha), soluble TNF receptors, interleukin (IL)-6, IL-1 receptor antagonist, and cortisol. After endotoxin administration, the subjects showed a transient significant increase in the levels of anxiety (effect size [ES] = 0.55) and depressed mood (ES = 0.66). Verbal and nonverbal memory functions were significantly decreased (ES = 0.55 to 0.64). Significant positive correlations were found between cytokine secretion and endotoxin-induced anxiety (r = 0.49 to r = 0.60), depressed mood (r = 0.40 to r = 0.75), and decreases in memory performance (r = 0.46 to r = 0.68). CONCLUSIONS: In humans, a mild stimulation of the primary host defense has negative effects on emotional and memory functions, which are probably caused by cytokine release. Hence, cytokines represent a novel target for neuropsychopharmacological research.

Continuous improvement evaluation: a framework for multisite evaluation studies.

This article proposes the use of the continuous improvement evaluation (CIE), a framework for multisite demonstration or evaluation studies. This framework is designed for studying intervention programs that change during the evaluation. The development of family drug courts is provided as an example. CIE relies on outcome data collected over time and benchmarked across similar cases in comparison sites; thus, this study was designed to collect data on effectiveness of intervention programs at multiple sites and over time. A weight is calculated for similarity of any two cases based on features they share. In statistical process control charts, these weights are used to compare outcomes at the site against the average of similar cases in comparison groups. Once data are benchmarked, program staff meet to discuss process changes that have led to improvements in outcomes. To ensure that intervention programs have access to evaluation reports on demand, information technology is used to collect, clean, and pool data. Computers generate study reports, and evaluators review reports after release to clients. Statistical tools can be used to evaluate changing programs. Traditional evaluators may be concerned about some threats to validity associated with CIE. The article concludes with a discussion of typical threats to validity and how these threats are addressed in the CIE framework.

[The physiopathology of weight regulation during treatment with psychotropic drugs]. / Zur Pathophysiologie der Gewichtsregulation im Rahmen der Therapie mit Psychopharmaka.

Weight changes during pharmacological treatment are a well-known phenomenon and they have been an object of research since the 1950's. Weight gain occurs during treatment with drugs of different chemical structures and is an important problem when patients are treated with antidepressants, antipsychotics, or mood stabilizers. The clinical relevance of drug-induced weight changes is due to increased rates of morbidity and reduced treatment compliance. Regarding the underlying causes, the important role of neurotransmitter systems and in particular the blockade of serotonin and histamine receptors has been discussed since decades. Only recently, however, research has been started on the effects of psychotropic agents on major neuroendocrine systems involved in appetite and weight regulation. These studies suggest that the fat-cell derived hormone leptin might play an important role. Leptin signals to the brain the size of the adipose tissue and is probably the most important peripheral signal for the long-term regulation of weight. In addition to the neuroendocrine systems, weight gain induced by psychotropic agents might also involve immune modulators, in particular the proinflammatory cytokine tumor-necrosis-factor-alpha (TNF-alpha) and soluble TNF-receptors. Some psychotropic agents influence the TNF system very rapidly, already prior to any obvious increases in weight. Hence, changes in the TNF-alpha system might be of predictive value for drug-induced weight gain. Strategies to minimize or to counteract weight gain induced by psychotropic agents include psychotherapeutic and pharmacological approaches. Although numerous psychotherapeutic approaches are available, they are only of limited usefulness in severely ill psychiatric patients. Fortunately, a number of promising pharmacological approaches to reduce weight have been introduced into clinical practice during the last years; however, so far there is no knowledge on pharmacodynamic and -kinetic interactions with psychotropic drugs, and there is no clinical data on the usefulness and safety of such drug combinations.