Treatment of Metaphyseal Defects in Plated Proximal Humerus Fractures with a New Augmentation Technique-A Biomechanical Cadaveric Study.

Background and Objectives: Unstable proximal humerus fractures (PHFs) with metaphyseal defects-weakening the osteosynthesis construct-are challenging to treat. A new augmentation technique of plated complex PHFs with metaphyseal defects was recently introduced in the clinical practice. This biomechanical study aimed to analyze the stability of plated unstable PHFs augmented via implementation of this technique versus no augmentation. Materials and Methods: Three-part AO/OTA 11-B1.1 unstable PHFs with metaphyseal defects were created in sixteen paired human cadaveric humeri (average donor age 76 years, range 66-92 years), pairwise assigned to two groups for locked plate fixation with identical implant configuration. In one of the groups, six-milliliter polymethylmethacrylate bone cement with medium viscosity (seven minutes after mixing) was placed manually through the lateral window in the defect of the humerus head after its anatomical reduction to the shaft and prior to the anatomical reduction of the greater tuberosity fragment. All specimens were tested biomechanically in a 25° adduction, applying progressively increasing cyclic loading at 2 Hz until failure. Interfragmentary movements were monitored by motion tracking and X-ray imaging. Results: Initial stiffness was not significantly different between the groups, p = 0.467. Varus deformation of the humerus head fragment, fracture displacement at the medial humerus head aspect, and proximal screw migration and cut-out were significantly smaller in the augmented group after 2000, 4000, 6000, 8000 and 10,000 cycles, p ≤ 0.019. Cycles to 5° varus deformation of the humerus head fragment-set as a clinically relevant failure criterion-and failure load were significantly higher in the augmented group, p = 0.018. Conclusions: From a biomechanical standpoint, augmentation with polymethylmethacrylate bone cement placed in the metaphyseal humerus head defect of plated unstable PHFs considerably enhances fixation stability and can reduce the risk of postoperative complications.

A Novel Technique for Treatment of Metaphyseal Voids in Proximal Humerus Fractures in Elderly Patients.

Background and Objectives: The treatment of proximal humerus fractures in elderly patients is challenging, with reported high complication rates mostly related to implant failure involving screw cut-out and penetration. Metaphyseal defects are common in osteoporotic bone and weaken the osteosynthesis construct. A novel technique for augmentation with polymethylmethacrylate (PMMA) bone cement was developed for the treatment of patients in advanced age with complex proximal humerus fractures and metaphyseal voids, whereby the cement was allowed to partially cure for 5-7 min after mixing to achieve medium viscosity, and then it was manually placed into the defect through the traumatic lateral window with a volume of 4-6 mL per patient. The aim of this retrospective clinical study was to assess this technique versus autologous bone graft augmentation and no augmentation. Materials and Methods: The outcomes of 120 patients with plated Neer three- and four-part fractures, assigned to groups of 63 cases with no augmentation, 28 with bone graft augmentation and 29 with cement augmentation, were assessed in this study. DASH, CS, pain scores and range of motion were analyzed at 3, 6 and 12 months. Statistical analysis was performed with factors for treatment and age groups, Neer fracture types and follow-up periods, and with the consideration of age as a covariate. Results: DASH and CS improved following cement augmentation at three and six months compared to bone grafting, being significant when correcting for age as a covariate (p ≤ 0.007). While the age group had a significant effect on both these scores with worsened values at a higher age for non-augmented and grafted patients (p ≤ 0.044), this was not the case for cement augmented patients (p ≥ 0.128). Cement augmentation demonstrated good clinical results at 12 months with a mean DASH of 10.21 and mean CS percentage of 84.83% versus the contralateral side, not being significantly different among the techniques (p ≥ 0.372), despite the cement augmented group representing the older population with more four-part fractures. There were no concerning adverse events specifically related to the novel technique. Conclusions: This study has detailed a novel technique for the treatment of metaphyseal defects with PMMA cement augmentation in elderly patients with complex proximal humerus fractures and follow-up to one year, whereby the cement was allowed to partially cure to achieve medium viscosity, and then it was manually placed into the defect through the traumatic lateral window. The results demonstrate clinically equivalent short-term results to 6 months compared to augmentation with bone graft or no augmentation-despite the patient group being older and with a higher rate of more severe fracture patterns. The technique appears to be safe with no specifically related adverse events and can be added in the surgeon's armamentarium for the treatment of these difficult to manage fractures.

Prognostic Relevance of Cardiopulmonary Exercise Testing for Patients with Chronic Thromboembolic Pulmonary Hypertension.

Background: Following acute pulmonary embolism (PE), a relevant number of patients experience decreased exercise capacity which can be associated with disturbed pulmonary perfusion. Cardiopulmonary exercise testing (CPET) shows several patterns typical for disturbed pulmonary perfusion. Research question: We aimed to examine whether CPET can also provide prognostic information in chronic thromboembolic pulmonary hypertension (CTEPH). Study Design and Methods: We performed a multicenter retrospective chart review in Germany between 2002 and 2020. Patients with CTEPH were included if they had ≥6 months of follow-up and complete CPET and hemodynamic data. Symptom-limited CPET was performed using a cycle ergometer (ramp or Jones protocol). The association of anthropometric data, comorbidities, symptoms, lung function, and echocardiographic, hemodynamic, and CPET parameters with survival was examined. Mortality prediction models were calculated by Cox regression with backward selection. Results: 345 patients (1532 person-years) were included; 138 underwent surgical treatment (pulmonary endarterectomy or balloon pulmonary angioplasty) and 207 received only non-surgical treatment. During follow-up (median 3.5 years), 78 patients died. The death rate per 1000 person-years was 24.9 and 74.2 in the surgical and non-surgical groups, respectively (p < 0.001). In age- and sex-adjusted Cox regression analyses, CPET parameters including peak oxygen uptake (VO2peak, reflecting cardiopulmonary exercise capacity) were prognostic in the non-surgical group but not in the surgical group. In mortality prediction models, age, sex, VO2peak (% predicted), and carbon monoxide transfer coefficient (% predicted) showed significant prognostic relevance in both the overall cohort and the non-surgical group. In the non-surgical group, Kaplan−Meier analysis showed that patients with VO2peak below 53.4% predicted (threshold identified by receiver operating characteristic analysis) had increased mortality (p = 0.007). Interpretation: The additional measurement of cardiopulmonary exercise capacity by CPET allows a more precise prognostic evaluation in patients with CTEPH. CPET might therefore be helpful for risk-adapted treatment of CTEPH.

LaRA 2: parallel and vectorized program for sequence-structure alignment of RNA sequences.

BACKGROUND: The function of non-coding RNA sequences is largely determined by their spatial conformation, namely the secondary structure of the molecule, formed by Watson-Crick interactions between nucleotides. Hence, modern RNA alignment algorithms routinely take structural information into account. In order to discover yet unknown RNA families and infer their possible functions, the structural alignment of RNAs is an essential task. This task demands a lot of computational resources, especially for aligning many long sequences, and it therefore requires efficient algorithms that utilize modern hardware when available. A subset of the secondary structures contains overlapping interactions (called pseudoknots), which add additional complexity to the problem and are often ignored in available software. RESULTS: We present the SeqAn-based software LaRA 2 that is significantly faster than comparable software for accurate pairwise and multiple alignments of structured RNA sequences. In contrast to other programs our approach can handle arbitrary pseudoknots. As an improved re-implementation of the LaRA tool for structural alignments, LaRA 2 uses multi-threading and vectorization for parallel execution and a new heuristic for computing a lower boundary of the solution. Our algorithmic improvements yield a program that is up to 130 times faster than the previous version. CONCLUSIONS: With LaRA 2 we provide a tool to analyse large sets of RNA secondary structures in relatively short time, based on structural alignment. The produced alignments can be used to derive structural motifs for the search in genomic databases.

Value of Cardiopulmonary Exercise Testing in the Prognosis Assessment of Chronic Obstructive Pulmonary Disease Patients: A Retrospective, Multicentre Cohort Study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is one of the most common chronic diseases associated with high mortality. Previous studies suggested a prognostic role for peak oxygen uptake (VO2peak) assessed during cardiopulmonary exercise testing (CPET) in patients with COPD. However, most of these studies had small sample sizes or short follow-up periods, and despite their relevance, CPET parameters are not included in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) tool for assessment of severity. OBJECTIVES: We therefore aimed to assess the prognostic value of CPET parameters in a large cohort of outpatients with COPD. METHODS: In this retrospective, multicentre cohort study, medical records of patients with COPD who underwent CPET during 2004-2017 were reviewed and demographics, smoking habits, GOLD grade and category, exacerbation frequency, dyspnoea score, lung function measurements, and CPET parameters were documented. Relationships with survival were evaluated using Kaplan-Meier analysis, Cox regression, and receiver operating characteristic (ROC) curves. RESULTS: Of a total of 347 patients, 312 patients were included. Five-year and 10-year survival probability was 75% and 57%, respectively. VO2peak significantly predicted survival (hazard ratio: 0.886 [95% confidence interval: 0.830; 0.946]). The optimal VO2peak threshold for discrimination of 5-year survival was 14.6 mL/kg/min (area under ROC curve: 0.713). Five-year survival in patients with VO2peak <14.6 mL/kg/min versus ≥ 14.6 mL/kg/min was 60% versus 86% in GOLD categories A/B and 64% versus 90% in GOLD categories C/D. CONCLUSIONS: We confirm that VO2peak is a highly significant predictor of survival in COPD patients and recommend the incorporation of VO2peak into the assessment of COPD severity.

Prognostic value of cardiopulmonary exercise testing in patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a severe rheumatic disease of the interstitial tissue, in which heart and lung involvement can lead to disease-specific mortality. Our study tests the hypothesis that in addition to established prognostic factors, cardiopulmonary exercise testing (CPET) parameters, particularly peak oxygen uptake (peakVO2) and ventilation/carbon dioxide (VE/VCO2)-slope, can predict survival in patients with SSc. SUBJECTS AND METHODS: We retrospectively assessed 210 patients (80.9% female) in 6 centres over 10 years with pulmonary testing and CPET. Survival was analysed with Cox regression analysis (adjusted for age and gender) by age, comorbidity (Charlson-Index), body weight, body-mass index, extensive interstitial lung disease, pulmonary artery pressure (measured by echocardiography and invasively), and haemodynamic, pulmonary and CPET parameters. RESULTS: Five- and ten-year survival of SSc patients was 93.8 and 86.9%, respectively. There was no difference in survival between patients with diffuse (dcSSc) and limited cutaneous manifestation (lcSSc; p = 0.3). Pulmonary and CPET parameters were significantly impaired. Prognosis was worst for patients with pulmonary hypertension (p = 0.007), 6-min walking distance < 413 m (p = 0.003), peakVO2 < 15.6 mL∙kg- 1∙min- 1, and VE/VCO2-slope > 35. Age (hazard ratio HR = 1.23; 95% confidence interval CI: 1.14;1.41), VE/VCO2-slope (HR = 0.9; CI 0.82;0.98), diffusion capacity (Krogh factor, HR = 0.92; CI 0.86;0.98), forced vital capacity (FVC, HR = 0.91; CI 0.86;0.96), and peakVO2 (HR = 0.87; CI 0.81;0.94) were significantly linked to survival in multivariate analyses (Harrell's C = 0.95). This is the first large study with SSc patients that demonstrates the prognostic value of peakVO2 < 15.6 mL∙kg- 1∙min- 1 (< 64.5% of predicted peakVO2) and VE/VCO2-slope > 35.

The SeqAn C++ template library for efficient sequence analysis: A resource for programmers.

BACKGROUND: The use of novel algorithmic techniques is pivotal to many important problems in life science. For example the sequencing of the human genome (Venter et al., 2001) would not have been possible without advanced assembly algorithms and the development of practical BWT based read mappers have been instrumental for NGS analysis. However, owing to the high speed of technological progress and the urgent need for bioinformatics tools, there was a widening gap between state-of-the-art algorithmic techniques and the actual algorithmic components of tools that are in widespread use. We previously addressed this by introducing the SeqAn library of efficient data types and algorithms in 2008 (Döring et al., 2008). RESULTS: The SeqAn library has matured considerably since its first publication 9 years ago. In this article we review its status as an established resource for programmers in the field of sequence analysis and its contributions to many analysis tools. CONCLUSIONS: We anticipate that SeqAn will continue to be a valuable resource, especially since it started to actively support various hardware acceleration techniques in a systematic manner.

Deformation behavior of Re alloyed Mo thin films on flexible substrates: In situ fragmentation analysis supported by first-principles calculations.

A major obstacle in the utilization of Mo thin films in flexible electronics is their brittle fracture behavior. Within this study, alloying with Re is explored as a potential strategy to improve the resistance to fracture. The sputter-deposited Mo1-xRex films (with 0 ≤ x ≤ 0.31) were characterized in terms of structural and mechanical properties, residual stresses as well as electrical resistivity. Their deformation behavior was assessed by straining 50 nm thin films on polyimide substrates in uniaxial tension, while monitoring crack initiation and propagation in situ by optical microscopy and electrical resistance measurements. A significant toughness enhancement occurs with increasing Re content for all body-centered cubic solid solution films (x ≤ 0.23). However, at higher Re concentrations (x > 0.23) the positive effect of Re is inhibited due to the formation of dual-phase films with the additional close packed A15 Mo3Re phase. The mechanisms responsible for the observed toughness behavior are discussed based on experimental observations and electronic structure calculations. Re gives rise to both increased plasticity and bond strengthening in these Mo-Re solid solutions.

Infected tibia defect fractures treated with the Masquelet technique.

The treatment after open and infected fractures with extensive soft tissue damage and bone deficit remains a challenging clinical problem. The technique described by Masquelet, using a temporary cement spacer to induce a membrane combined with reconstructive soft tissue coverage, is a possible solution. This study describes the work-up, operative procedure, complications, and the outcome of a homogenous group of patients with an open and infected tibia fracture and segmental bone loss treated with the Masquelet technique (MT).This retrospective study evaluates patients having sustained an open tibia fracture treated with the MT between 2008 and 2013 with a follow up of at least 1 year. The defect was either primary, caused by a high-grade open fracture or secondary due to a non-union after an open fracture. Prerequisite conditions prior to the procedure of the Masquelet were a defect zone with eradicated infection, an intact soft tissue cover and stability provided by an external fixation.Volume of the defect, time until the implantation of the spacer, time of the spacer in situ and the time to clinical and radiological union were evaluated. Patient records were screened for reoperations and complications. The functional clinical outcome was measured.Eight patients were treated with a follow up over 1 year. The spacer was implanted after a median of 11 (2-70) weeks after the accident. The predefined conditions for the Masquelet phase were reached after a median of 12 (7-34) operations.Seven patients required reconstructive soft tissue coverage. The volume of the defect had a median of 111 (53.9-621.6) cm, the spacer was in situ for a median of 12 (7-26) weeks. Radiological healing was achieved in 7 cases after a median time of 52 (26-93) weeks.Full weight bearing was achieved after a median time of 16 (11-24) weeks. Four patients needed a reoperation. The lower limb functional index was a median of 60% (32-92%).Seven out of 8 patients treated in this group of severe open and infected tibia fractures did both clinically and radiologically heal. Due to the massive destruction of the soft tissue, patients needed several reoperations with soft tissue debridements and reconstruction before the spacer and the bone graft could be implanted.

Cardiopulmonary exercise testing for detecting pulmonary arterial hypertension in systemic sclerosis.

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a devastating disease with limited survival and occurs as a frequent complication in patients with systemic sclerosis (SSc). A definite diagnosis of PAH is obtained by right heart catheterisation (RHC); however, the initial suspicion is raised by non-invasive methods. We assessed the diagnostic accuracy of key parameters derived from cardiopulmonary exercise testing (CPET) for detecting and ruling out SSc-associated PAH. METHODS: In a multicentre setting, we prospectively evaluated 173 consecutive patients with SSc without known PAH, but with clinical suspicion of PAH. Each patient underwent CPET and RHC. RESULTS: RHC identified PAH in 48 patients (27.8%), postcapillary pulmonary hypertension (PH) in 10 patients (5.8%) and ruled out PH in 115 patients (66.5%). CPET parameters correlated significantly with pulmonary haemodynamics. PeakVO2 and VE/VCO2 showed highest correlations with pulmonary arterial pressure, transpulmonary pressure gradient and pulmonary vascular resistance. Several parameters showed high sensitivity and specificity for PAH detection by receiver operating characteristic analysis. However, peakVO2 showed highest diagnostic accuracy (sensitivity 87.5%, specificity 74.8% at a threshold level of 13.8 mL/min/kg). A peakVO2 of >18.7 mL/kg/min was reached by 38/173 patients (22%) and excluded PAH in our cohort (negative predictive value 1.0). A nadir VE/VCO2 ratio of >45.5 showed a positive predictive value of 1.0. Diagnostic accuracy was highest in patients with low pulmonary arterial wedge pressure (<12 mm Hg). There were no study-related serious adverse events. CONCLUSIONS: CPET is a safe and valuable method in the non-invasive detection of SSc-associated PAH. It may be particularly beneficial for reducing unnecessary RHC procedures.

High levels of dioxin-like PCBs found in organic-farmed eggs caused by coating materials of asbestos-cement fiber plates: A case study.

During a regional monitoring project of organic-farmed, free-range and cage-free eggs, high levels of dioxin-like compounds were detected in organic-farmed eggs, using the dioxin responsive chemical-activated luciferase gene expression (DR-CALUX®) bioassay. Further evaluations performed with GC-HRMS (gas chromatography in combination with high resolution mass spectrometry) revealed elevated amounts of non-dioxin-like (non-dl) polychlorinated biphenyls (PCBs) dominated by most lipophilic congeners like PCB 138, 153 and 180 and of dioxin-like (dl) PCBs, with a congener pattern in the descending order of PCB 118, 156, 167, 105, 189, 157, 105, 126 and PCB 77. Contaminations with polychlorinated dibenzo-p-dioxins (PCDDs) appeared of minor priority, with only hepta- and octa-substituted dioxins above their limits of quantification (LOQs). The pattern of polychlorinated dibenzofurans (PCDFs) was dominated by low amounts of tetra- and penta-chlorinated congeners. To identify the source of contamination, several samples of organic-farmed eggs, soil, laying hens, feedstuff, corrugated asbestos-cement cover plates (ACPs), stable dust and debris collected in the gutter of the stable, were analyzed. Comparing PCB congener-pattern of individual samples, the source was traced back to the coating of ACPs, which covered roof and sidewalls of the stable. Because coating materials probably have been used for roofing and cladding in many countries worldwide, there is a high probability that the presented case report is not a local incident but rather describes a new source of PCB contamination, yet widely unknown or underestimated.

Incremental prognostic value of cardiopulmonary exercise testing and resting haemodynamics in pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease despite recent treatment advances. Individual risk stratification is important. Exercise capacity and invasive haemodynamic data are both relevant, but data on the combined prognostic power are lacking. METHODS: 226 consecutive patients with idiopathic or familial PAH were included at seven specialised tertiary centres. All patients underwent right heart catheterization and cardiopulmonary exercise testing (CPET). RESULTS: During follow-up (1508 ± 1070 days) 72 patients died and 30 underwent transplantation. On multivariate analysis percentage of predicted peak oxygen uptake (%predicted peak VO2 [risk ratio 0.95]), pulmonary vascular resistance (PVR [1.105,]) and increase in heart rate during exercise (ΔHR [0.974]) were independent prognostic predictors (all p<0.0001). Peak VO2 allowed for risk stratification with a survival of 100, 92.9, 87.4 and 69.6% at 1 year and 97.7, 63.2, 41 and 23% at 5 years for the 4th, 3rd, 2nd and 1st quartiles, respectively. Dichotomizing by median peak VO2 and intra-group median PVR showed a worse 1-year survival for patients with low peak VO2/higher PVR compared to patients with low peak VO2/low PVR, high peak VO2/high PVR and high peak VO2/low PVR (65 vs. 93, 93, 100%, p<0.001). At 10 years survival was different for all 4 subgroups (19 vs. 25 vs. 48 vs. 75%, adjusted p<0.05). CONCLUSIONS: Peak VO2, PVR and ΔHR independently predict prognosis in patients with PAH. Low peak VO2, high PVR and low ΔHR refer to poor prognosis. Combined use of peak VO2 and PVR provides accurate risk stratification underlining the complementary prognostic information from cardiopulmonary exercise testing and resting invasive haemodynamic data.

TGF-ß and RPE-derived cells in taut subretinal strands from patients with proliferative vitreoretinopathy.

PURPOSE: To investigate the distribution of transforming growth factor-ß (TGF-ß) and cells derived from the retinal pigment epithelium (RPE) as a major source for TGF-ß in subretinal strands (SRSs), originating from patients with proliferative vitreoretinopathy (PVR) and proliferative diabetic vitreoretinopathy (PDVR). METHODS: Nine SRSs (PVR: n=6 and PDVR: n=3) were obtained during pars plana vitrectomy. Specimens were processed for immunohistochemical analysis in paraffin wax or studied by transmission electron microscopy. RESULTS: Staining for TGF-ß was consistent in all specimens. The content of RPE-derived cells identified by anticytokeratin staining revealed considerable differences, ranging from <10 to >90%. CONCLUSIONS: The widespread immunoreactivity for TGF-ß in SRSs suggests a significant role of this group of cytokines in the pathologic course of PVR.

Non-invasive diagnosis of pulmonary hypertension: ESC/ERS Guidelines with Updated Commentary of the Cologne Consensus Conference 2011.

The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the diagnosis of pulmonary hypertension. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the non-invasive diagnosis of pulmonary hypertension. This manuscript describes in detail the results and recommendations of the working group which were last updated in October 2011.

Long-term therapy with inhaled iloprost in patients with pulmonary hypertension.

AIMS: To investigate the long-term safety of inhaled iloprost in patients with pulmonary hypertension (pH), including idiopathic PAH (IPAH group) and other forms of pulmonary hypertension (PHother). METHODS AND RESULTS: Sixty-three patients (IPAH group, n=40, PHother n=23) were enrolled to receive inhaled iloprost either from baseline or after 3 months in a prospective, open-label 2-year study. Iloprost was inhaled 6-9 times daily with a night pause employing a jet nebulizer delivering an inhaled single dose of 4microg at the mouthpiece. In the case of side effects the single dose was reduced to 2microg. Sixty patients received at least 1 dose of inhaled iloprost. Thirty-six patients completed at least 630 days of therapy (25 IPAH, 11 PHother), 19 patients dropped out prematurely and 8 patients died (3 IPAH, 5 PHother). There were no drug-induced toxicities and only mild to moderate side effects. The most common side effects were coughing and flushing. Two-year survival was estimated at 85% (IPAH group 91%, PHother 78%). A modified analysis was performed to correct for differential drop-out. It included follow-up data from the premature discontinuations and revealed a 2-year survival of 87% [95% CI, 76%-98%] in the IPAH group while the predicted survival was 63%. The iloprost dose increased by 16% over 2 years. CONCLUSION: Inhaled iloprost is well tolerated as long-term therapy and no substantial dose increase is required. Although uncontrolled, the data suggest a long-term clinical benefit from continued therapy with inhaled iloprost.

[Pulmonary and pleural tuberculosis in the elderly]. / Tuberkulose der Lunge und Pleura im Alter.

With the increase of the proportion of the elderly in the total population more cases of pulmonary and extrapulmonary tuberculosis (TB) are observed in this age group as well. Symptoms of TB are unspecific, often less apparent in the elderly, and may therefore cause a delay in the diagnostic process. A history of TB and comorbidities are more common in elder as compared to younger TB patients. The tuberculin skin test is less frequently positive. The interferon-gamma-release assay is complementary and together with clinical, radiologic, and bacteriologic test results helpful for the diagnosis or the exclusion of an active or latent TB infection. Medical treatment of TB in the elderly follows the established guidelines in the same way as for younger patients. The likelihood of drug-induced side effects and interactions with concomitant medications, however, is increased. Comorbidity and age-related immunosuppression may lead to a delay in the healing process. Higher age, comorbidity, and immunosuppression are predictors of an increased TB mortality. Even in a low-incidence country like Germany, TB should be recognized as an explanation for clinical symptoms particularly in the elderly patient group in order to allow an early diagnosis and therapy and thus a reduction of mortality and prevention of a further spread of this disease.

[Spectrum of tuberculous diseases in a pulmonary outpatient clinic]. / Spektrum tuberkulöser Erkrankungen in der pneumologischen Praxis.

BACKGROUND: Although the incidence of 6.6 newly diagnosed tuberculosis (TB) cases per 100,000 inhabitants is in decline in Germany, TB remains a disease of significant epidemiologic importance. PATIENTS AND METHODS: From 04/2001 to 07/2008, a total of 75 TB patients of an internal-pulmonary outpatient clinic had been treated (0.5% of all patients). 58 (77.3%) patients fulfilled the criteria of an active TB, 17 (22.7%) of latent tuberculous infection (LTBI). 68.0% were male (average age men 39.3 +/- 16.9 years [mean +/- standard deviation], women 46.8 +/- 21.5 years; p = not significant). 69.3% of the patients were born in Germany, 30.7% abroad. 84.5% patients had isolated pulmonary, 8.6% additional organ involvement, and 6.9% isolated extrapulmonary TB. 62.1% of active TB cases were microbiologically proven (51.7% microscopically, 43.1% in addition culturally, 6.9% exclusively culturally, 19.0% by polymerase chain reaction [PCR]). RESULTS: Of 23 tests, 52.2% were fully sensitive against the most important first-line drugs ethambutol (M), isoniazid (H), rifampicin (R), pyrazinamide (Z), und streptomycin (S). 13.0% had an isolated resistance against H (4.4%) or S (8.6%), 4.4% a multiple drug resistance (MDR) against R und H, 30.4% a polyresistance (S and H). Symptoms were quite often unspecific, not taken care of, or misinterpreted. CONCLUSION: Diagnosis and therapy of an active or latent TB illness remains, an important task and challenge, necessitating an effective cooperation of outpatient, hospital, and health authority institutions.

Comparative evaluation of life cycle assessment models for solid waste management.

This publication compares a selection of six different models developed in Europe and America by research organisations, industry associations and governmental institutions. The comparison of the models reveals the variations in the results and the differences in the conclusions of an LCA study done with these models. The models are compared by modelling a specific case - the waste management system of Dresden, Germany - with each model and an in-detail comparison of the life cycle inventory results. Moreover, a life cycle impact assessment shows if the LCA results of each model allows for comparable and consecutive conclusions, which do not contradict the conclusions derived from the other models' results. Furthermore, the influence of different level of detail in the life cycle inventory of the life cycle assessment is demonstrated. The model comparison revealed that the variations in the LCA results calculated by the models for the case show high variations and are not negligible. In some cases the high variations in results lead to contradictory conclusions concerning the environmental performance of the waste management processes. The static, linear modelling approach chosen by all models analysed is inappropriate for reflecting actual conditions. Moreover, it was found that although the models' approach to LCA is comparable on a general level, the level of detail implemented in the software tools is very different.

Continuous intravenous iloprost to revert treatment failure of first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension.

AIMS: To describe the clinical and haemodynamic effects during the first 6 months of continuous intravenous iloprost treatment in patients with idiopathic pulmonary arterial hypertension (IPAH) and relevant disease progression despite continued mono therapy with aerosolized iloprost. METHODS AND RESULTS: Twenty-four IPAH patients with clinical decompensation to NYHA class IV despite therapy with aerosolized iloprost and optimized conservative treatment were assessed clinically, haemodynamically and by cardiopulmonary exercise testing for at least 6 months. Upon switching from inhaled to intravenous iloprost all patients improved clinically (NYHA III) while pulmonary vascular resistance (PVR) and right atrial pressure decreased from 2386 +/- 243 to 1381 +/- 124 dyne .s .cm(-5) and 12 +/- 1 to 8.5 +/- 1 mmHg, respectively (both p < 0.05). Despite this acute improvement haemodynamic (PVR increased from 1462+/-223 to 1978 +/- 327 dyne .s .cm(-5)) and clinical (4 deaths, 4 transplantations) deterioration occurred with continued intravenous treatment during the following 6 months. CONCLUSIONS: In the group of patients described in this report the clinical and haemodynamic deterioration occurring while on mono therapy with inhaled iloprost could be stopped by switching to continuous application of intravenous iloprost. However, with continued intravenous therapy only a subgroup of patients could clinically be stabilized and transplanted successfully.