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Background Cervical spine injuries (CSI) are rare in trauma patients, at about 9.2–16.5/100,000 inhabitants in Scandinavia and Canada, and the annual incidence of CSI surgeries in Norway is around 3.0/100,000 inhabitants. However, despite their rarity, the incidence of CSI has increased, thereby assuming an increasing need for surgery. Outside of Scandinavia, no data about the incidence of CSI and subsequent surgeries exist. Therefore, this study aimed to analyse CSI epidemiology and surgery in a German city with a Level I trauma centre both to understand the injury and improve needs–based planning. Methods This retrospective, monocentre study included all patients who presented with CSI from 2012–2017 at a university hospital with a Level I trauma centre in a major German city and had permanent residency within the city. Based on the assumption that the patients represented all CSI injuries in the city, as they were treated at the only available Level I trauma centre, the annual incidence of surgeries and neurologic deficits due to CSI were calculated. Results A total of 465 patients with 609 CSI were identified. Of these patients, 61 both received surgery and resided in the city (mean age, 68.1 ± 18.3 years; 26 female, 35 male). The incidence of CSI surgeries was calculated as 3.24/100,000 person years (1.75/100,000 in the upper and 1.54/100,000 in the subaxial cervical spine). Neurologic deficits occurred in 0.64/100,000 person years. The incidence of both surgeries and neurologic deficits showed no significant changes over the 6-year study period. Conclusions Compared to Scandinavia, an increasing annual incidence for CSI surgeries and neurologic deficits were found. For long-term demand planning with adaptability to demographic changes, cross-regional studies including long-term follow-up are necessary.

Breath analysis holds promise for non-invasivein vivomonitoring of disease related processes. However, physiological parameters may considerably affect profiles of exhaled volatile organic substances (VOCs). Volatile substances can be released via alveoli, bronchial mucosa or from the upper airways. The aim of this study was the systematic investigation of the influence of different sampling sites in the respiratory tract on VOC concentration profiles by means of a novel experimental setup.After ethical approval, breath samples were collected from 25 patients undergoing bronchoscopy for endobronchial ultrasound or bronchoscopic lung volume reduction from different sites in the airways. All patients had total intravenous anaesthesia under pressure-controlled ventilation. If necessary, respiratory parameters were adjusted to keep PETCO2= 35–45 mm Hg. 30 ml gas were withdrawn at six sampling sites by means of gastight glass syringes: S1 = Room air, S2 = Inspiration, S3 = Endotracheal tube, S4 = Trachea, S5 = Right B6 segment, S6 = Left B6 segment (S4–S6 through the bronchoscope channel). 10 ml were used for VOC analysis, 20 ml for PCO2determination. Samples were preconcentrated by solid-phase micro-extraction (SPME) and analysed by gas chromatography–mass spectrometry (GC-MS). PCO2was determined in a conventional blood gas analyser.Statistically significant differences in substance concentrations for acetone, isoprene, 2-methyl-pentane and n-hexane could be observed between different sampling sites. Increasing substance concentrations were determined for acetone (15.3%), 2-methyl-pentane (11.4%) and n-hexane (19.3%) when passing from distal to proximal sampling sites. In contrast, isoprene concentrations decreased by 9.9% from proximal to more distal sampling sites. Blank bronchoscope measurements did not show any contaminations.Increased substance concentrations in the proximal respiratory tract may be explained through substance excretion from bronchial mucosa while decreased concentrations could result from absorption or reaction processes. Spatial mapping of VOC profiles can provide novel insights into substance specific exhalation kinetics and mechanisms.

Background The histologic diagnosis of Pulmonary Langerhans cell histiocytosis (PLCH) is invasive and can cause complications. To confirm the diagnosis of PLCH, guidelines therefore recommend measuring CD1a-positive bronchoalveolar lavage fluid (BALF) cells despite its poor sensitivity and specificity. Thus, an improved diagnostic accuracy of BALF cell analysis would be desirable. Methods Using four-colour flow cytometry, plasmacytoid and myeloid dendritic cells (DCs) were analysed in BALF of 10 newly diagnosed, untreated, smoking patients with PLCH, and compared with BALF DCs from 40 asymptomatic smokers and 21 never-smokers. Results Compared with controls, myeloid DCs (median: 0.79% of BALF leukocytes) and their subpopulation of Langerhans cells (median: 0.44% of BALF leukocytes) were not increased in PLCH. Patients with PLCH displayed a normal expression of the maturity marker CD83 on BALF myeloid DCs. However, the expression of the co-signaling molecule CD80 on BALF myeloid DCs was significantly lower than in both control groups, with the lowest expression found in more severe disease (presence of cysts > 2 cm in diameter). Based on receiver operating characteristic (ROC) curve analysis, a cut-off of 53% CD80-positive BALF myeloid DCs was optimal for the diagnosis of PLCH, yielding a sensitivity of 0.90 and a specificity of 0.90. Conclusions BALF Langerhans cells are not increased in PLCH. However, PLCH is characterised by a low expression of CD80 on BALF myeloid DCs. Due to its considerably higher sensitivity and specificity, this marker appears to be more appropriate to diagnose PLCH than the currently recommended marker CD1a.

Background Although hospitalisations due to an exacerbation of chronic obstructive pulmonary disease (COPD) are associated with increased risk of mortality, there is little information on long-term survival after severe COPD exacerbations. Methods The 5-year and 8-year overall survival after hospitalisation due to a COPD exacerbation was explored. In addition, potential predictors of survival were analysed. Results The 57 patients with COPD included in this analysis had a median age of 70 years, a median smoking history of 30 pack years and a median forced expiratory volume in the first second (FEV 1 ) of 41.6% predicted at the time of COPD exacerbation. The majority of the patients had either normal weight (body mass index, BMI 18.5–24.99 kg/m 2 : 42%) or overweight (BMI ≥ 25 kg/m 2 : 54%). The 5-year overall survival after exacerbation was 54%, the 8-year overall survival 42%. The presence of cardiac comorbidities, a FEV 1 70 years and a BMI 2 , but not smoking history or current smoking, were associated with decreased overall survival. Multivariate regression analysis revealed that only BMI, age and FEV 1 were independent predictors of long-term survival. Overweight patients (BMI ≥ 25 kg/m 2 ) had a substantially higher 5-year overall survival (74%) than patients with a BMI 2 (31%). Conclusion Nearly half of the patients hospitalised due to an exacerbation of COPD die within 5 years after the event. Overweight is a positive predictor of long-term survival in these patients.

Novel treatment strategies are currently emerging for patients with inadequately controlled asthma despite good adherence and trigger avoidance. These strategies serve primarily to reduce or completely avoid long-term oral corticosteroid therapy. A number of these options have already been implemented in practice or will soon be authorized for the treatment of asthma, while others still need to prove their clinical practicability, safety and efficacy. The present article provides an overview of the broad spectrum of novel inhaled, oral, systemic, and invasive treatment strategies for asthma.

Fur Patienten, welche trotz einer leitliniengerechten Therapie, einer guten Adharenz und einer effektiven Meidung von Triggerfaktoren ein nicht ausreichend kontrolliertes Asthma aufweisen, wurden in den letzten Jahren neue Therapiestrategien entwickelt. Diese dienen insbesondere der Reduktion oder vollstandigen Vermeidung einer dauerhaften oralen Glukokortikoidtherapie. Einige dieser Optionen haben die Praxis bereits erreicht oder werden demnachst zur Behandlung von Asthma zugelassen, andere Optionen mussen ihre Praxistauglichkeit, Sicherheit und Nachhaltigkeit noch unter Beweis stellen. Der vorliegende Artikel gibt einen Uberblick uber das breite Spektrum an neuen inhalativen, oralen, systemischen und invasiven Therapiestrategien bei Asthma.

Here, we report that increasing treatment with inhaled corticosteroids (ICS) in patients with not well-controlled asthma from a medium to a high dose results in a profound reduction of blood eosinophils (median fall in blood eosinophil concentrations from 560 to 320 cells/µL). Therefore, ‘normal values’ of blood eosinophils in patients with asthma need to be considered in view of the individual ICS doses of the patients. In addition, increases in the dose of ICS may result in blood eosinophil concentrations which would formally preclude treatment with biologics targeting the interleukin-5 pathway.

We report the case of a nosocomial infection due to Enterococcus cecorum isolated from a blood culture of a 75-year-old septic male patient. Matrix-assisted laser desorption–ionization time-of-flight mass spectrometry (MALDI-TOF MS) and Vitek 2 succeeded in identification of the isolate.

Enzyme-linked immunosorbent assay (ELISA) is a standard immunoassay to estimate protein concentrations in a variety of samples. An automated ELISA procedure was established that allows the measurement of the concentration of numerous proteins in a small sample volume. The automated ELISA procedure was tested by measuring the concentration of brain-derived neurotrophic factor in serum samples from humans. It was shown that the reproducibility of protein concentrations in three assay plates within one automated run was greater than 92%, within independent automated experiments greater than 96%. Automated processing with a maximum capacity of six plates and 240 serum samples per run showed an average interassay precision of 91 %. Serial dilutions of randomly chosen sera displayed significant linearity of recovered concentration. In conclusion it can be stated that the automated assay provides high flexibility with highly reproducible results and has several advantages compared to the manual method, including less operator dependence and faster sample throughput. The investigated ELISA test system seems to exhibit analytical characteristics indicating further clinical application. (JALA 2007;12:219–29)

Background: Beneficial effects of the anti-IgE antibody omalizumab in asthma are partly explained by a suppression of the expression of the high-affinity IgE receptor on plasmacytoid dendritic cells (DCs). However, the expression of this receptor on DCs in chronic obstructive pulmonary disease (COPD) is unknown. Methods: Using four-colour flow cytometry, high-affinity IgE receptor expression on myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in peripheral blood was analysed in 64 patients with COPD (median age: 65 years; median FEV 1 : 45.8 % predicted) and in control groups of 41 asymptomatic never-smokers, 21 asymptomatic current smokers and 20 patients with allergic asthma. Results: Asymptomatic current smokers displayed a significantly increased expression of the high-affinity IgE receptor on mDCs and pDCs, as compared with never-smokers. In patients with COPD, the expression of the high-affinity IgE receptor on pDCs, but not mDCs, increased with from spirometric GOLD stage II to IV, and correlated with lung function impairment. In patients with spirometric GOLD stages III and IV, the expression of the high-affinity IgE receptor on pDCs did not significantly differ from patients with allergic asthma. In all groups, there was a significant correlation between total IgE serum concentrations and the expression of the high-affinity IgE receptor on pDCs, suggesting that this correlation is a general feature in humans. Conclusion: The elevated expression of the high-affinity IgE receptor on plasmacytoid DCs in severe COPD is comparable with the expression in allergic asthma. Possible implications of this finding for therapies targeting IgE require further investigation.

Background The reduction of asthma exacerbations following omalizumab treatment has been related to the suppression of the high-affinity IgE receptor (FceRI) on plasmacytoid dendritic cells (DCs). However, the FceRI expression on DCs in chronic obstructive pulmonary disease (COPD) is unknown. Objective To compare FceRI expression on DCs in COPD with patients with allergic asthma and healthy controls, and to relate the findings to clinical parameters, blood eosinophil concentrations and serum immunoglobin E (IgE) concentrations. Methods Using four-colour flow cytometry, FceRI expression on blood myeloid DCs and plasmacytoid DCs was analysed in 64 patients with COPD, 20 patients with allergic asthma, 41 asymptomatic never-smokers and 21 asymptomatic current smokers. Results As compared with never-smokers, current smokers displayed an increased expression of the FceRI on myeloid and plasmacytoid DCs. In patients with COPD, the expression of the FceRI on plasmacytoid DCs, but not myeloid DCs, increased from spirometric GOLD stage 2 to GOLD stage 4, and was correlated with several lung function parameters. Patients with severe COPD and patients with allergic asthma displayed a similar FceRI overexpression on plasmacytoid DCs. In all groups, there was a positive correlation between total IgE serum concentrations and the FceRI expression on plasmacytoid DCs. Conclusions & Clinical Relevance Severe COPD and allergic asthma are characterised by a similar overexpression of the high-affinity IgE receptor on plasmacytoid DCs. In view of the effect of anti-IgE on exacerbations in asthma, trials investigating the effect of anti-IgE on exacerbations in severe COPD appear to be warranted. This article is protected by copyright. All rights reserved.

Background Dendritic cells (DCs) control immunity and play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the expression of function-associated surface molecules on circulating DCs in COPD is unknown. Methods Four-colour flow cytometry was used to compare blood DC surface molecules of 54 patients with COPD (median age: 59 years; median FEV1: 38% predicted, median CAT score: 24) with two age-matched control groups with normal lung function: 21 current smokers and 21 never-smokers. Results Concentrations of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not differ between the groups. The increased expression of BDCA-1, BDCA-3, CD86 and CCR5 on mDCs in patients with COPD did not significantly differ from smokers with normal lung function. In contrast, COPD was specifically characterised by a decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on mDCs. These changes were not confined to patients with elevated systemic inflammation markers (leukocytes, c-reactive protein, interleukin-6, fibrinogen). The ratio of OX40L to PD-L1 expression (OX40L/PD-L1 ratio), a quantitative measure of imbalanced DC co-stimulation, correlated with the severity of pulmonary emphysema in patients with COPD. Conclusion An imbalance of DC co-stimulation might contribute to the pathogenesis of COPD. Electronic supplementary material The online version of this article (doi:10.1186/s12931-015-0174-x) contains supplementary material, which is available to authorized users.

Background: Patients with obstructive sleep apnoea syndrome (OSAS) often display persistent cognitive dysfunction despite effective treatment with continuous positive airway pressure (CPAP). Brain-derived neurotrophic factor (BDNF) is a key mediator of memory and cognition, but its regulation in OSAS and during CPAP treatment is unknown. Methods: Serum and plasma BDNF concentrations, BDNF secretion by peripheral blood mononuclear cells, and overnight polysomnography were evaluated in 17 men with newly diagnosed OSAS (as defined by a respiratory disturbance index of >10/hour with >70% obstructive events and corresponding daytime symptoms) and 12 healthy control men. In the patients all the parameters were monitored after 1 night and 3 months of CPAP treatment. Results: There was no significant difference in baseline serum BDNF, plasma BDNF, or spontaneous BDNF secretion by peripheral blood mononuclear cells between untreated patients and controls. After 1 night of CPAP treatment there was a steep fall in median serum BDNF (from 18.0 ng/ml to 4.1 ng/ml) and plasma BDNF (from 58.7 pg/ml to 22.0 pg/ml) concentrations. Following 3 months of treatment BDNF concentrations did not return to baseline. In contrast, BDNF secretion was not suppressed by CPAP treatment. Conclusions: Patients with untreated OSAS have normal serum and plasma BDNF levels. CPAP treatment is associated with a rapid decrease in serum and plasma BDNF levels which may reflect enhanced neuronal demand for BDNF in this condition.

Anti-platelet treatment is a key therapeutic intervention in patients with cerebrovascular diseases. However, there is no information on its impact on the release of Brain-derived neurotrophic factor (BDNF), which is stored in large amounts in human platelets and essential for neuronal protection and repair. Here, we show that a single oral dose of clopidogrel, but not aspirin, significantly reduced the release of BDNF from platelets in healthy volunteers. These data point, for the first time, to possible differential effects of anti-platelet regimens on neuronal function in patients with cerebrovascular disorders.

Extracellular ATP promotes inflammation, but its role in chronic obstructive pulmonary disease (COPD) is unknown.To analyze the expression of ATP and its functional consequences in never-smokers, asymptomatic smokers, and patients with COPD.ATP was quantified in bronchoalveolar lavage fluid (BALF) of never-smokers, asymptomatic smokers, and patients with COPD of different severity. The expression of specific ATP (purinergic) receptors was measured in airway macrophages and blood neutrophils from control subjects and patients with COPD. The release of mediators by macrophages and neutrophils and neutrophil chemotaxis was assessed after ATP stimulation.Chronic smokers had elevated ATP concentrations in BALF compared with never-smokers. Acute smoke exposure led to a further increase in endobronchial ATP concentrations. Highest ATP concentrations in BALF were present in smokers and ex-smokers with COPD. In patients with COPD, BALF ATP concentrations correlated negatively with lung function and positively with BALF neutrophil counts. ATP induced a stronger chemotaxis and a stronger elastase release in blood neutrophils from patients with COPD, as compared with control subjects. In addition, airway macrophages from patients with COPD responded with an increased secretion of proinflammatory and tissue-degrading mediators after ATP stimulation. These findings were accompanied by an up-regulation of specific purinergic receptors in blood neutrophils and airway macrophages of patients with COPD.COPD is characterized by a strong and persistent up-regulation of extracellular ATP in the airways. Extracellular ATP appears to contribute to the pathogenesis of COPD by promoting inflammation and tissue degradation.

Airway dendritic cells (DCs) play a key role in smoke-related lung diseases; however, the acute effects of tobacco smoke on human airway DCs in vivo are unknown. A total of 16 smokers underwent bronchoalveolar lavage at two time-points: directly after a 4-h period of nonsmoking (no smoke exposure); and directly after a 4-h period during which eight cigarettes were smoked (acute smoke exposure). Using flow cytometry, myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), as well as function-associated surface molecules on mDCs, were analysed in bronchoalveolar lavage fluid (BALF) and in blood. The numbers of macrophages, lymphocytes, neutrophils, eosinophils and pDCs were unchanged in BALF following acute smoke exposure, as compared to no smoke exposure. In contrast, there was a strong increase in mDC number in BALF and a concomitant decrease in mDC number in blood following acute smoke exposure. In addition, acute smoke exposure led to an increase in the expression of the surface molecules blood dendritic cell antigen 1 and 4 and a decrease in the expression of the lung homing receptor, CC chemokine receptor 5, on mDCs in BALF. Acute tobacco smoke inhalation results in an immediate and selective recruitment of mDCs into human airways, which might reflect the very early reaction of the adaptive immune system to smoke exposure.

A novel method of computer-assisted video image analysis (VIA) was used to determine the number of immunostained cells in tissue sections. This method permitted an accurate and objective quantification of cells of a particular phenotype. This enumeration was achieved by measuring the area stained by a test monoclonal antibody (such as the T cell marker, CD3) and comparing it with the area stained by a leukocyte common (LCA) monoclonal antibody (CD45). The proportion of T cells within the total leukocyte population in a particular tissue was then calculated. The differentiation of positive (stained) and negative (unstained) cells was uniformly maintained by setting the computer to detect a threshold for staining intensity. This enabled consistency to be maintained within a tissue section as well as between sections stained with the same antibody. In the present study, we determined the phenotype of leukocytes in colonic carcinomas by VIA and compared this with results obtained by normal visual analysis. The VIA method showed distinct advantages over normal visual analysis especially in sections which contained moderate numbers of stained cells.

Background Chronic Obstructive Pulmonary Disease (COPD) is characterised by complex inflammatory, neuronal and fibrotic changes. Brain-derived Neurotrophic Factor (BDNF) is a key regulator of neuronal plasticity, whereas Transforming Growth Factor-β1 (TGF-β1) plays a crucial role in tissue repair and emphysema pathogenesis. Both mediators are stored in platelets and released from platelets in inflammatory conditions and during serum preparation. In patients with asthma, it was previously shown that elevated serum BDNF concentrations correlate with disease severity, whereas TGF-β1 concentrations were normal. Methods In the present study, 63 patients with stable COPD (spirometric GOLD stages 2–4) and 17 age- and comorbidity-matched controls were studied. Lung function, smoking history, medication, platelet concentrations in peripheral blood and serum concentrations of BDNF, TGF-β1 and Serotonin (5-HT) were assessed in all participants. Results Serum levels of both BDNF and TGF-β1 (but not concentrations of platelets in peripheral blood) were significantly elevated in all stages of COPD as compared to controls. Highest BDNF concentrations were found in spirometric GOLD stage 3, whereas highest TGF-β1 serum levels were found in spirometric GOLD stage 4. There were specific, stage-dependent correlations of these mediators with lung function parameters of the patients. Conclusions Taken together, we show that, in contrast to asthma, COPD is characterised by elevated concentrations of both BDNF and TGF-β1 in serum. The stage-dependent association with lung function supports the hypothesis that these platelet mediators may play a role in the pathogenesis of COPD.

To the Editor: In their Image in Clinical Medicine, Zalts and Hayek (Dec. 18 issue)1 describe a woman with postpartum venous thromboembolism. The patient was found to be heterozygous for a mutation...

A series of pyridines were synthesized and evaluated as bronchospasmolytic / anti-allergic agents. Several of these compounds were found to: 1) inhibit the release of histamine; 2) antagonize histamine, bradykinin, LTD4 and PAF; 3) suppress the IgE-mediated passive cutaneous anaphylaxis (PCA) reaction. The most interesting substance of this series 2,6-dimethyl-3-nitro-4[(2-(4-diphenylmethyl-1-piperazinyl)ethyl)amino]pyridine 1, (HWA 214), was selected for further pharmacological evaluation. The novel, orally active agent 1 does not have such drawbacks as causing drowsiness or being effective only as a prophylactic drug, and could provide advantages over other non-sedative compounds, such as terfenadine and astemizole, in that it is water soluble and thus can be administered through inhalation or through intravenous application.