Prevalence of pre-operative anaemia in surgical patients: a retrospective, observational, multicentre study in Germany.

Anaemia is a risk factor for several adverse postoperative outcomes. Detailed data about the prevalence of anaemia are not available over a long time-period in Germany. In this retrospective, observational, multicentre study, patients undergoing surgery in March in 2007, 2012, 2015, 2017 and 2019 were studied. The primary objective was the prevalence of anaemia at hospital admission. The secondary objectives were the association between anaemia and the number of units of red blood cells transfused, length of hospital stay and in-hospital mortality. A total of 23,836 patients were included from eight centres. The prevalence of pre-operative anaemia in patients aged ≥ 18 years decreased slightly from 37% in 2007 to 32.5% in 2019 (p = 0.01) and increased in patients aged ≤ 18 years from 18.8% in 2007 to 26.4% in 2019 (p > 0.001). The total amount of blood administered per 1000 patients decreased from 671.2 units in 2007 to 289.0 units in 2019. Transfusion rates in anaemic patients declined from 33.8% in 2007 to 19.1% in 2019 (p < 0.001) and in non-anaemic patients from 8.4% in 2007 to 3.4% in 2019 (p < 0.001). Overall, the mortality rate remained constant over the years: 2.9% in 2007, 2.1% in 2012, 2.5% in 2015, 1.9% in 2017 and 2.5% in 2019. In the presence of anaemia, mortality was significantly increased compared with patients without anaemia (OR 5.27 (95%CI 4.13-6.77); p < 0.001). Red blood cell transfusion was associated with an increased risk of mortality (OR 14.98 (95%CI 11.83-19.03); p < 0.001). Using multivariable linear regression analysis with fixed effects, we found that pre-operative anaemia (OR 2.08 (95%CI 1.42-3.05); p < 0.001) and red blood cell transfusion (OR 4.29 (95%CI 3.09-5.94); p < 0.001) were predictors of mortality but not length of stay (0.99 (95%CI 0.98-1.00) days; p = 0.12) and analysed years (2007 vs. 2019: OR 1.49 (95%CI 0.86-2.69); p = 0.07). Pre-operative anaemia affects more than 30% of surgical patients in Germany and multidisciplinary action is urgently required to reduce adverse outcomes.

[Bed capacity management in times of the COVID-19 pandemic : A simulation-based prognosis of normal and intensive care beds using the descriptive data of the University Hospital Augsburg]. / Bettenkapazitätssteuerung in Zeiten der COVID-19-Pandemie : Eine simulationsbasierte Prognose der Normal- und Intensivstationsbetten anhand der deskriptiven Daten des Universitätsklinikums Augsburg.

BACKGROUND: Following the regional outbreak in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world, presenting the healthcare systems with huge challenges worldwide. In Germany the coronavirus diseases 2019 (COVID-19) pandemic has resulted in a slowly growing demand for health care with a sudden occurrence of regional hotspots. This leads to an unpredictable situation for many hospitals, leaving the question of how many bed resources are needed to cope with the surge of COVID-19 patients. OBJECTIVE: In this study we created a simulation-based prognostic tool that provides the management of the University Hospital of Augsburg and the civil protection services with the necessary information to plan and guide the disaster response to the ongoing pandemic. Especially the number of beds needed on isolation wards and intensive care units (ICU) are the biggest concerns. The focus should lie not only on the confirmed cases as the patients with suspected COVID-19 are in need of the same resources. MATERIAL AND METHODS: For the input we used the latest information provided by governmental institutions about the spreading of the disease, with a special focus on the growth rate of the cumulative number of cases. Due to the dynamics of the current situation, these data can be highly variable. To minimize the influence of this variance, we designed distribution functions for the parameters growth rate, length of stay in hospital and the proportion of infected people who need to be hospitalized in our area of responsibility. Using this input, we started a Monte Carlo simulation with 10,000 runs to predict the range of the number of hospital beds needed within the coming days and compared it with the available resources. RESULTS: Since 2 February 2020 a total of 306 patients were treated with suspected or confirmed COVID-19 at this university hospital. Of these 84 needed treatment on the ICU. With the help of several simulation-based forecasts, the required ICU and normal bed capacity at Augsburg University Hospital and the Augsburg ambulance service in the period from 28 March 2020 to 8 June 2020 could be predicted with a high degree of reliability. Simulations that were run before the impact of the restrictions in daily life showed that we would have run out of ICU bed capacity within approximately 1 month. CONCLUSION: Our simulation-based prognosis of the health care capacities needed helps the management of the hospital and the civil protection service to make reasonable decisions and adapt the disaster response to the realistic needs. At the same time the forecasts create the possibility to plan the strategic response days and weeks in advance. The tool presented in this study is, as far as we know, the only one accounting not only for confirmed COVID-19 cases but also for suspected COVID-19 patients. Additionally, the few input parameters used are easy to access and can be easily adapted to other healthcare systems.

Validity and sensitivity to change of laser Doppler imaging as a novel objective outcome measure for cutaneous lupus erythematosus.

OBJECTIVES: The objectives of this study were to assess the reliability of a novel objective outcome measure, laser Doppler imaging (LDI), its validity against skin biopsy histology and other clinical instruments, including localized cutaneous lupus disease area and severity index (L-CLASI) and visual analogue scale (VAS) score of photographs, and its responsiveness to clinical change with therapy. METHODS: A prospective observational cohort study was conducted in 30 patients with active cutaneous lupus erythematosus (CLE). At baseline and 3 months, disease activity was assessed using L-CLASI and a high resolution LDI system by two assessors. Skin biopsy was scored as 0 = non-active, 1 = mild activity and 2 = active. Photographs were assessed by two clinicians using 100 mm VAS. Inter-rater reliability was analyzed using Bland-Altman limits of agreement. Correlation between histology and LDI, L-CLASI and VAS and sensitivity to change of LDI with physician subjective assessment of change (PSAC) at 3 months were analyzed using Kendall's tau-a. RESULTS: Of 30 patients with CLE, 28 (93%) were female, mean (SD) age 48.4 (11.5) y, 25 (83%) were Caucasians, 25 (83%) had concurrent systemic lupus erythematosus and 16 (53%) were smokers. CLE subtypes were acute = 9, subacute = 8 and chronic = 13. Inter-rater agreement for LDI was fair but for VAS score of photographs was poor. In 20 patients with biopsy, correlation with histology was better for LDI (tau-a = 0.53) than L-CLASI (tau-a = 0.26) (difference = 0.27; 90% CI 0.05-0.49) or VAS score of photographs (tau-a = 0.17) (difference = 0.36; 90% CI 0.04-0.68). There was a moderate correlation between PSAC score and change in LDI (tau-a = 0.56; 90% CI 0.38-0.74; p < 0.001, n = 15). CONCLUSION: LDI provides a reliable, valid and responsive quantitative measure of inflammation in CLE. It has a better correlation with histology compared to clinical instruments. LDI provides an objective outcome measure for clinical trials.

Assessing health status over time: impact of recall period and anchor question on the minimal clinically important difference of copd health status tools.

BACKGROUND: The Minimal Clinically Important Difference (MCID) assesses what change on a measurement tool can be considered minimal clinically relevant. Although the recall period can influence questionnaire scores, it is unclear if it influences the MCID. This study is the first to examine longitudinally the impact of the recall period of an anchor question and its design on the MCID of COPD health status tools using the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and the St. George's Respiratory Questionnaire (SGRQ). METHODS: Moderate to very severe COPD patients without respiratory co-morbidities were recruited during 3-week Pulmonary Rehabilitation (PR). CAT, CCQ and SGRQ were completed at baseline, discharge, 3, 6, 9 and 12 months. A 15-point Global Rating of Change scale (GRC) was completed at each follow-up. A five-point GRC was used as second anchor at 12 months. Mean change scores of a subset of patients indicating a minimal improvement on each of the anchor questions were considered the MCID. The MCID estimates over different time periods were compared with one another by evaluating the degree of overlap of Confidence Intervals (CI) adjusted for dependency. RESULTS: In total 451 patients were included (57.9 ± 6.6 years, 65% male, 50/39/11% GOLD II/III/IV), of which 309 completed follow-up. Baseline health status scores were 20.2 ± 7.3 (CAT), 2.9 ± 1.2 (CCQ) and 50.7 ± 17.3 (SGRQ). MCID estimates for improvement ranged - 3.1 to - 1.4 for CAT, - 0.6 to - 0.3 for CCQ, and - 10.3 to - 7.6 for SGRQ. Absolute higher - though not significant - MCIDs were observed for CAT and CCQ directly after PR. Significantly absolute lower MCID estimates were observed for CAT (difference - 1.4: CI -2.3 to - 0.5) and CCQ (difference - 0.2: CI -0.3 to -0.1) using a five-point GRC. CONCLUSIONS: The recall period of a 15-point anchor question seemed to have limited impact on the MCID for improvement of CAT, CCQ and SGRQ during PR; although a 3-week MCID estimate directly after PR might lead to absolute higher values. However, the design of the anchor question was likely to influence the MCID of CAT and CCQ. TRIAL REGISTRATION: RIMTCORE trial # DRKS00004609 and #12107 (Ethik-Kommission der Bayerischen Landesärztekammer).

EEG correlates of cognitive time scales in the Necker-Zeno model for bistable perception.

The Necker-Zeno model of bistable perception provides a formal relation between the average duration of meta-stable percepts (dwell times T) of ambiguous figures and two other basic time scales (t0, ΔT) underlying cognitive processing. The model predicts that dwell times T covary with t0, ΔT or both. We tested this prediction by exploiting that observers, in particular experienced meditators, can volitionally control dwell times T. Meditators and non-meditators observed bistable Necker cubes either passively or tried to hold their current percept. The latencies of a centro-parietal event-related potential (CPP) were recorded as a physiological correlate of t0. Dwell times T and the CPP latencies, correlated with t0, differed between conditions and observer groups, while ΔT remained constant in the range predicted by the model. The covariation of CPP latencies and dwell times, as well as their quadratic functional dependence extends previous psychophysical confirmation of the Necker-Zeno model to psychophysiological measures.

Treatment of severe, chronic hand eczema: results from a UK-wide survey.

Treatment of severe hand eczema (HE) that is resistant to topical potent corticosteroid treatment is challenging. In 2013, we surveyed 194 UK dermatologists to obtain information about their usual treatment pathways to inform the choice of the comparator in a trial of alitretinoin in severe HE (ALPHA trial); the results indicated that the treatment approaches favoured by UK dermatologists differ. Psoralen combined with ultraviolet A (PUVA) and alitretinoin were identified as the most frequent first-line treatment options for hyperkeratotic HE, whereas oral corticosteroids were identified as the most frequent first-line treatment for vesicular HE, followed by PUVA and alitretinoin. In terms of potential adverse effects of long-term or repeated use, oral steroids and ciclosporin A were reported to cause most concern. There is uncertainty about which treatment gives the best short and long-term outcomes, because of a lack of definitive randomised controlled trials evaluating the effectiveness of different treatment pathways in severe HE.

[Patient Satisfaction as a Measure of Quality of Patient Care - Comparison between a University Hospital and a General Hospital]. / Patientenzufriedenheit als Maßeinheit im Qualitätsmanagement ­ ein Vergleich zwischen einem Universitätsklinikum und einem Krankenhaus der Regelversorgung.

Objective: The aim of the study was to compare the satisfaction of patients of a general hospital with a university hospital. A patient satisfaction index was calculated based on the assessed levels of satisfaction. In general, higher satisfaction could lead to increased competitiveness and improved cost efficiency for achieving profitability. Methods: The authors developed and administered a questionnaire on distinct parameters presumed to reflect the quality of the hospital stay to patients of a university hospital (University Hospital of Bonn, UKB, 1 224 beds) and a general hospital (Johanniterkrankenhaus, Bonn, JKH, 364 beds). Data were collected anonymously. Patient satisfaction and the relative importance of each parameter were assessed. The quotient of both parameters yields the patient satisfaction index (PZI). In order to account for possible differences in patient demands, statistical analysis was performed. Results: The demands and wishes, satisfaction and importance of the retrieved parameters did not differ significantly between the patients of the hospitals in any of aspects assessed (information, participation, contact and comfort during the hospital-stay). The study showed that communication and the contact to physicians and nurses was significantly more important for the patients than comfort (each p<0.001). The highest PZI were found in the categories entertainment (UKB 1.02; JKH 1.25) and contact to the nursing personnel (PZI UKB 0.94; PZI JKH 0.96). The standard of medical-technical care (UKB 0.93; JKH 0.95) was also highly ranked by patients of both hospitals. Needs for improvement related especially to the communication of errors (UKB 0.33; JKH 0.31). Discussion: Surveillance of patient wishes and criticism may result in a more patient-oriented care on a daily basis. Scrutinizing the resources employed may lead to more efficient use of resources and personnel and thus help cut costs and improve the attractiveness of hospitals.

Infrared spectroscopy via substrate-integrated hollow waveguides: a powerful tool in catalysis research.

Substrate-integrated hollow waveguides (iHWG) represent an innovative generation of photon conduits, which can simultaneously serve as highly miniaturized gas cells with low sample volume. In this communication, we introduce a novel concept for analyzing the performance of catalysts via infrared gas phase analysis based on iHWGs. Due to rapid gas exchange and sample transient times within the iHWG, compositional changes of a continuous gas stream after interaction with a catalyst assembly can be monitored with high time resolution.

Recovery from prolonged deep rocuronium-induced neuromuscular blockade: A randomized comparison of sugammadex reversal with spontaneous recovery.

BACKGROUND: Deep neuromuscular blockade (NMB) may not always be maintained to the end of surgery and the depth of block may be allowed to gradually diminish over time, particularly if reversal of NMB is not routinely performed. AIM: The current study aimed to assess recovery from deep rocuronium-induced NMB with sugammadex compared with placebo, provide data regarding the extent of residual blockade after deep rocuronium-induced NMB (placebo group), and to determine whether complete and reliable recovery could be provided by sugammadex (sugammadex group). MATERIALS AND METHODS: This was a randomized, placebo-controlled, safety-assessor-blinded study in adult patients of American Society of Anesthesiologists Class I to III. Patients with clinically relevant kidney or liver insufficiency were excluded. Anesthesia was administered as routinely practiced at each study site. Rocuronium 0.6 mg/kg was administered for intubation, with maintenance doses of 0.1-0.2 mg/kg as needed. After the last rocuronium dose, at deep NMB (target depth 1-2 post-tetanic counts), patients received a single dose of sugammadex 4.0 mg/kg or placebo as randomized. The primary endpoint was time from sugammadex or placebo administration to recovery of the train-of-four (TOF) ratio to 0.9. Safety was assessed through monitoring of adverse events, vital signs and physical examination. Patients were also assessed for evidence of residual or recurrence of NMB. With this design, the study will provide data regarding the extent of residual blockade under these conditions (placebo group), and determine whether complete and reliable recovery could be provided by sugammadex (sugammadex group). RESULTS: Recovery to a TOF ratio of ≥ 0.9 with sugammadex was significantly faster (~ 40 times) than spontaneous recovery: geometric mean (95 % confidence interval) times were 2.2 (1.9-2.5) and 89.8 (80.1-100.7) min, respectively (p < 0.0001, N = 134); maximum spontaneous recovery was 289.8 min. Safety was comparable between groups, with no recurrence of blockade. CONCLUSIONS: This study confirms a prolonged residual blockade in patients who did not receive sugammadex, with median time to recovery > 1.5 h in the placebo group and one patient taking 4.8 h to achieve a safe level of neuromuscular function recovery following deep NMB. In contrast, sugammadex provided complete and reliable recovery of neuromuscular function (median time to recovery of 2.0 min). Thus, deep NMB with rocuronium until the end of the operation may be possible in combination with sugammadex reversal.

[Robotic vs. laparoscopic right hemicolectomy-An analysis of costs]. / Robotische vs. laparoskopische Hemikolektomie rechts ­ eine Kostenanalyse.

The use of robotic surgical methods for performing right-sided hemicolectomy has been somewhat controversial, primarily due to concerns related to costs. The purpose of this study is to document the initial robotic right hemicolectomies conducted at our institution and to compare them with a laparoscopic reference group. A significant focus of this study is the detailed analysis of the costs associated with both techniques within the German healthcare system.Surgical and cost-related data for 34 cases each for robotic and laparoscopic right-sided hemicolectomy performed at Nürnberg Hospital were compared. This comparison was conducted through a retrospective single-center case-matched analysis. Cost analysis was carried out following the current guidelines provided by the Institute for the Hospital Remuneration System (InEK) of Germany.The average age of the patient cohort was 70 years, with a male patient proportion of 57.4%. Analysis of perioperative parameters indicated similar outcomes for both surgical techniques. Regarding the incidence of complications of Clavien-Dindo stages III-V (8.8% vs. 17.6%; p = 0.48), a positive trend towards robotic surgery was observed. The cost analysis showed nearly identical total costs for the selected cases in both groups (mean €13,423 vs. €13,424; p = 1.00), with the most significant cost difference noted in surgical (operative) costs (€5,779 vs. €3,521; p < 0.01). The lower costs for laparoscopic cases were primarily due to the reduced material costs (mean €2,657 vs. €702; p < 0.05).In conclusion, both surgical approaches are clinically equivalent, with only minor differences in the total case costs.

Optimal table feed in run-off CT angiography in patients with abdominal aortic aneurysms.

OBJECTIVES: To assess the influence of different table feeds (TFs) on vascular enhancement and image quality in patients with an abdominal aortic aneurysm (AAA) undergoing computed tomography (CT) angiography of the lower extremities (run-off CTA). METHODS: Seventy-nine patients (71 ± 8 years) with an AAA (>30 mm) who underwent run-off CTA between January 2004 and August 2011 were included in this retrospective institutional review board-approved study. Run-off CTA was conducted using 16- and 64-row CT. The range of TFs was 30-86 mm/s and was categorised in quartiles TF1 (32.6 ± 1.9 mm/s), TF2 (38.9 ± 0.9 mm/s), TF3 (43.9 ± 3.1 mm/s) and TF4 (57.4 ± 10.5 mm/s). Image quality was rated independently by two radiologists and vessel enhancement was assessed. RESULTS: Image quality was diagnostic at all aortic, pelvic and almost all thigh levels. Below the knee, the number of diagnostic levels was highest for TF1 and decreased to TF4. Arterial enhancement between the aorta and fibular trunk was not different in all TF groups, P > 0.05. At the calf and foot strongest arterial enhancement was noted for TF1 and TF2 and decreased to TF4, P < 0.01. CONCLUSION: Results indicate that the highest image quality of run-off CTA in patients with an AAA may be obtained using table feeds measuring 30-35 mm/s. KEY POINTS: • CTA has become a key investigation for peripheral vascular disease. • Run-off CTA is more complex in patients with an abdominal aortic aneurysm. • Run-off CTA is feasible with a short bolus of intravenous contrast medium. • A constant 30-35 mm/s table feed provides the highest likelihood of diagnostic images.

Evaluation of continuous ampicillin/sulbactam infusion in critically ill patients.

Continuous infusion (CI) of beta-lactam-antibiotics may improve pharmacodynamics in critically ill patients, but resulting concentrations have not been studied. Therapeutic drug monitoring is increasingly used to ensure antibiotic concentration. The aim of this study is to evaluate therapeutic ampicillin/sulbactam concentrations of a continuous infusion regimen. METHODS: Medical records of all patients admitted to ICU between January 2019 and December 2020 were retrospectively reviewed. Each patient received a 2/1 g ampicillin/sulbactam loading dose, followed by a continuous infusion of 8/4 g per 24 h. Ampicillin serum concentrations were measured. Main outcomes were reaching of plasma concentrations breakpoint defined by minimum inhibitory concentration (MIC at 8 mg/l) and 4-fold MIC (MIC at 32 mg/l) during steady state of CI. RESULTS: In 50 patients a total of 60 concentration measurements were performed. The first concentration was measured after a median of 29 h (IQR 21-61 h). Mean ampicillin concentration was 62.6 ± 39.1 mg/l. Furthermore, serum concentrations exceeded the defined MIC breakpoint in all measurements (100 %) and were above the 4-fold MIC in 43 analyses (71.1 %). However, patients suffering from acute kidney injury exhibited significant higher serum concentrations (81.1 ± 37.7 mg/l vs. 38.2 ± 24.8 mg/l; p < 0.001). Also, there was a negative correlation between ampicillin serum concentrations and GFR (r = -0.659; p < 0.001). CONCLUSION: The described dosing regimen for ampicillin/sulbactam is safe with respect to the defined MIC breakpoints for ampicillin, and continuous subtherapeutic concentration is unlikely. However, with impaired renal function drug accumulation occurs, and with increased renal clearance, drug levels can be below the 4-fold MIC breakpoint.

Interleukin-33 modulates the expression of human ß-defensin 2 in human primary keratinocytes and may influence the susceptibility to bacterial superinfection in acute atopic dermatitis.

BACKGROUND: Interleukin (IL)-33 is a member of the IL-1 family and has been implicated in Th2-driven allergic diseases such as atopic dermatitis (AD) and asthma. The principal Th2 cytokine IL-4, found highly expressed in acute allergic eczema, is known to downregulate human ß-defensin 2 (hBD2) expression in human keratinocytes and this is associated with superinfection in patients with AD. OBJECTIVES: To investigate the effect of IL-33 on the expression of hBD2 in human keratinocytes. METHODS: hBD2 production by stimulated keratinocytes was measured by enzyme-linked immunosorbent assay. RESULTS: Our results showed that serum is a very potent inducer of hBD2 and 2·5% human serum was much more potent in inducing hBD2 than 20 ng mL(-1) of tumour necrosis factor-α. Interestingly, serum from patients with AD showed an impaired ability to induce hBD2 in normal keratinocytes. IL-33 significantly downregulated serum-induced hBD2. The downregulatory capacity of IL-33 was found to be 1·5- to 2-fold weaker compared with IL-4. CONCLUSIONS: Our data suggest that IL-33 can significantly contribute to the decreased expression of hBD2 in acute eczematous reaction clinically characterized by spongiosis and oozing - thus indicative for contact of the epidermis with serum components.

[Student evaluation of anesthesiological teaching: steering instrument of a continuous improvement process]. / Studentische Evaluation der anästhesiologischen Lehre : Steuerinstrument eines kontinuierlichen Verbesserungsprozesses.

BACKGROUND: The amendment to the higher education act ("Hochschulrahmengesetz") of 1998 postulates an evaluation of teaching for quality assurance. Hence, in the winter semester of 2004 the University Medical Center of Bonn introduced a semester questionnaire for students to evaluate the quality of teaching (EVALON). This evaluation is designed to be an objective benchmarking tool which is used for the distribution of university funds. It is also a steering instrument for direct improvement of teaching in clinical subjects. The aim of this study was to investigate, whether EVALON improved the quality of teaching between 2006 and 2010 and whether the department of anesthesiology improved its ranking in comparison with the other participating institutes. MATERIALS AND METHODS: Data from the EVALON questionnaire from the years 2006-2010 were analyzed for improvements in the quality of teaching in anesthesiology. This study focused on three essential contents of the EVALON questionnaire (structural content and organizational procedure of lectures and seminars, course presentation), which were used for the generation of a ranking list of all participating medical institutes and departments. On the basis of these results, 12.5% of the funding was assigned for educational purposes. RESULTS: There was an average return rate of the questionnaires of 74.5%. A significant increase in the overall assessment score of 43.4% could be observed from 5.3 in the summer semester of 2006 to 7.6 in the winter semester of 2009/10. The evaluation score for the department of anesthesiology concerning structural content of seminars and lectures increased by 79% from 4.8 in 2006 to 8.6 in 2010. The quality of organizational procedure was evaluated with a score of 4.9 in 2006 and improved by 74% to 8.5 in 2010. The course presentation skills of the teachers as evaluated by EVALON improved by 61% from a score of 5.2 in 2006 to 8.4 in 2010. In comparison with all other participating medical institutes the department of anesthesiology improved its ranking from position 36 in the winter semester 2006 to position 2 in the summer semester 2010. CONCLUSIONS: The reorganization of teaching anesthesiology, directly controlled by the results of EVALON improved the ranking of the department of anesthesiology. There was also a concomitant increase of the performance-oriented allocation of funds assigned to the department of anesthesiology based on the EVALON results.

[Hypothermia under olanzapine treatment: clinical case series and review of current literature]. / Hypothermie unter Olanzapin : Eine Fallserie mit Literaturübersicht.

BACKGROUND: Antipsychotic drugs may lead to hypothermia as well as hyperthermia. Although known for decades and clinically highly relevant, the mechanisms by which antipsychotic drugs alter thermoregulatory processes in the human body are still far from being fully understood. In clinical practice, much attention is paid to antipsychotic drug-induced elevation of body core temperature as observed in the neuroleptic malignant syndrome (NMS). But also hypothermia is a clinically highly relevant adverse reaction to antipsychotic drugs. MATERIAL AND METHODS: Here we report a case series of three patients who developed severe hypothermia after administration of olanzapine. A review of the current literature is given with a focus on risk factors for the development of antipsychotic drug-induced hypothermia and its pathophysiologic mechanisms. RESULTS: A 51-year-old female patient suffering from catatonic schizophrenia, cachectic nutritional condition and hypothyroidism developed severe hypothermia of 30.0°C body core temperature after administration of 30 mg olanzapine per day under comedication with lorazepam and L-thyroxine. A 48-year-old female patient with catatonic schizophrenia showed hypothermia of 31.0°C (rectal measurement) after single-dose administration of olanzapine 10 mg orally and a total of 3 mg lorazepam (1-1-1 mg). The third case report describes a 69-year-old male patient with acute delusional disorder exhibiting hypothermia of 33.0°C (rectal measurement) in combination with a reversible atrioventricular block grade III without any further comedication. CONCLUSION: A review of the current literature reveals that thermoregulatory disturbances as sequelae of antipsychotic drug administration depend on individual disposition as well as various independent risk factors such as environmental temperature, somatic comorbidities, endocrinological abnormalities (e.g. hypothyroidism) and structural damage of the brain. A complex interaction of dopaminergic regulatory mechanisms in the ventral hypothalamus and peripheral vaso- and sudomotor adjustments seems to be causative. Hypothermia following antipsychotic drug administration represents a serious adverse drug reaction and a potentially life-threatening event.

Modulatory role of calreticulin as chaperokine for dendritic cell-based immunotherapy.

Heat shock proteins (HSPs) play a regulatory role for maturation of antigen-presenting cells (APCs) such as dendritic cells (DCs) and macrophages. Whereas HSP70 has been shown to enhance the maturation of human DCs via a nuclear factor kappa-B (NF-κB)-dependent pathway, the regulatory role of calreticulin (CRT), which is a HSP with similar functions to HSP70, is not well studied. To investigate the role of CRT as adjuvant in cell activation and co-stimulatory responses we determined the effects of CRT on human APC maturation in comparison to that of HSP70. To facilitate eukaryotic endotoxin-free CRT protein expression, three different methods were compared. We demonstrate that CRT induces the maturation of human DCs and increases the production of proinflammatory cytokines via the NF-κB pathway. CRT-mediated maturation was qualitatively similar to that induced by HSP70. Interestingly, priming of monocytes with HSPs showed an even more prominent effect on maturation than exposure of immature DCs to these compounds. A higher expression of CD86, CD83 and CCR7 on mature DCs were found in response to CRT. Our data provide novel insights into the role of extracellular HSPs as chaperokines in the processes of APC generation and may thus be useful to improve adoptive immunotherapy.

Expression of interleukin (IL)-1 family members upon stimulation with IL-17 differs in keratinocytes derived from patients with psoriasis and healthy donors.

BACKGROUND: A number of studies have challenged the T-cell-centred pathogenetic view of psoriasis by the finding that epithelium-expressed genes are intimately involved in the inflammatory process. Interleukin (IL)-17 is an important inflammatory mediator in skin psoriasis. OBJECTIVE: IL-17 is known to act on keratinocytes and we were interested in its impact on the expression of pro- and anti-inflammatory IL-1 family members. METHODS: We compared human keratinocytes derived from epidermal stem cells of hair follicles plucked from patients with psoriasis and healthy individuals using quantitative reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assays. RESULTS: In the presence of IL-17, psoriasis-derived keratinocytes showed a significantly higher induction of the proinflammatory IL-1 family members IL-1F6 and IL-1F9, but not of anti-inflammatory members IL-1F5, IL-1F7 or IL-1F3 compared with keratinocytes from healthy individuals. Both basal and IL-17-induced levels of IL-1F2 and IL-1F1 were found to be significantly lower in psoriasis keratinocytes. CONCLUSION: As keratinocytes were derived from epidermal stem cells of the hair follicles and were obtained from nonlesional sites, differences found are likely to present an intrinsic feature of psoriasis epithelium. Our data support the significance of IL-1 family members as therapeutic targets in psoriasis conditions.

Completed suicides in 47 psychiatric hospitals in Germany--results from the AGATE-study.

INTRODUCTION: There is an ongoing debate about a possibly enhanced risk of suicidal behaviour in some psychiatric patients due to psychopharmacotherapy. Our retrospective study aimed at analyzing the psychopharmacotherapy of 133 inpatient suicides and 133 controls by a matched pair design. METHODS: We analyzed all suicides (n = 133) reported in the AGATE study from 1991 to 2008. Besides evaluation of sociodemographic variables and suicide methods, we compared psychopharmacotherapy of suicides with schizophrenia (n = 59) and affective disorders (n = 59) to that of a matched control group. RESULTS: Most suicides (n = 102, 76.7%) were judged not to be related to psychopharmacotherapy. In general, more psychopharmacological drugs were prescribed for suicides than for controls. Schizophrenic suicides received more low potency FGAs than their controls. More suicides with affective disorders than controls were treated with NASSAs, SNRIs, and high or low potency FGAs. In contrast to their controls, none of the suicides with affective disorders received lithium. NASSAs, SNRIs, and high or low potency FGAs predicted suicide in regression analysis for inpatients with affective disorders. DISCUSSION: Differences in psychopharmacotherapy might mainly result from a recognized risk of suicide or a more severe degree of illness. However, the underrepresentation of lithium in the suicide groups is noticeable.

Preoccupation with death as predictor of psychological distress in patients with haematologic malignancies.

The purpose of the present study was to identify preoccupation with death in relation to levels of psychological distress in patients with haematologic malignancies. One hundred and two inpatients with haematologic malignancies, treated with curative intent, and thirty-three control inpatients with benign dysfunction participated in the present study. Psychological distress was measured with the Hospital Anxiety and Depression Scale and the Freiburg Questionnaire of Coping with Illness. Preoccupation with death was assessed with the Subjective Estimation of Sickness and Death Scale. Patients with haematologic malignancies had significantly more preoccupation with death than the control group. In patients with haematologic malignancies preoccupation with death was related to depressive coping style as well as symptoms of depression and anxiety; regression analyses reveal that the diagnosis of haematologic malignancy leads to stronger subjective feelings of being close to death, which in turn leads to more psychological distress. To the best of our knowledge this is the first study that quantitatively shows the existence of preoccupation with death in patients with haematologic malignancies and its association with psychological distress. Our findings indicate that patients who are treated with a curative regime need psychological intervention focusing on death-related fear in order to prevent severe emotional distress.

Interleukin-1 from epithelial cells fosters T cell-dependent skin inflammation.

BACKGROUND: Chronic inflammatory skin diseases such as atopic dermatitis and psoriasis are characterized by the infiltration of lymphocytes into the epidermal compartment. Several studies point to an active role of skin epithelial cells in the pathophysiology of such diseases. OBJECTIVES: In this study we addressed the regulatory function of primary human keratinocytes in the interaction with autologous T cells and monocytes. METHODS: We used a human coculture model with keratinocytes grown from epidermal stem cells of the outer root sheath of human hair follicles and autologous T cells. RESULTS: In our coculture system we observed a high production of interferon (IFN)-γ, but not Th2 cytokines, in the presence of superantigen or antigen-pulsed autologous monocytes. Critical parameters for this effect were: (i) T-cell receptor activation, (ii) an intercellular adhesion molecule-1/lymphocyte function-associated antigen (LFA)-1-dependent interaction between keratinocytes and T cells, and (iii) secretion of interleukin (IL)-1ß. Remarkably, in the presence of activated T cells, epithelial cells seemed to be a more significant source of IL-1ß than monocytes. Application of the LFA-1 blocker efalizumab or IL-1 receptor antagonist anakinra enabled us to suppress completely the production of IFN-γ by T cells in the coculture. CONCLUSIONS: IL-1 secretion and the physical contact between keratinocytes and activated, infiltrating T cells may be central for the development of chronic inflammatory skin conditions.