Management of patients with SARS-CoV-2 infections with focus on patients with chronic lung diseases (as of 10 January 2022) : Updated statement of the Austrian Society of Pneumology (ASP).

The Austrian Society of Pneumology (ASP) launched a first statement on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in May 2020, at a time when in Austria 285 people had died from this disease and vaccinations were not available. Lockdown and social distancing were the only available measures to prevent more infections and the breakdown of the health system. Meanwhile, in Austria over 13,000 patients have died in association with a SARS-CoV­2 infection and coronavirus disease 2019 (COVID-19) was among the most common causes of death; however, SARS-CoV­2 has been mutating all the time and currently, most patients have been affected by the delta variant where the vaccination is very effective but the omicron variant is rapidly rising and becoming predominant. Particularly in children and young adults, where the vaccination rate is low, the omicron variant is expected to spread very fast. This poses a particular threat to unvaccinated people who are at elevated risk of severe COVID-19 disease but also to people with an active vaccination. There are few publications that comprehensively addressed the special issues with SARS-CoV­2 infection in patients with chronic lung diseases. These were the reasons for this updated statement. Pulmonologists care for many patients with an elevated risk of death in case of COVID-19 but also for patients that might be at an elevated risk of vaccination reactions or vaccination failure. In addition, lung function tests, bronchoscopy, respiratory physiotherapy and training therapy may put both patients and health professionals at an increased risk of infection. The working circles of the ASP have provided statements concerning these risks and how to avoid risks for the patients.

Can simvastatin reduce COPD exacerbations? A randomised double-blind controlled study.

BACKGROUND: Several studies have shown that statins have beneficial effects in COPD regarding lung function decline, rates and severity of exacerbation, hospitalisation and need for mechanical ventilation. METHODS: We performed a randomised double-blind placebo-controlled single-centre trial of simvastatin at a daily dose of 40 mg versus placebo in patients with Global Initiative for Chronic Obstructive Lung Disease criteria grades 2-4 at a tertiary care pulmonology department in Austria. Scheduled treatment duration was 12 months and the main outcome parameter was time to first exacerbation. RESULTS: Overall, 209 patients were enrolled. In the 105 patients taking simvastatin, time to first exacerbation was significantly longer compared to the 104 patients taking placebo: median 341 versus 140 days (log-rank test p<0.001). Hazard ratio for risk of first exacerbation for the simvastatin group was 0.51 (95% CI 0.34-0.75; p=0.001). Rate of exacerbations was significantly lower with simvastatin: 103 (41%) versus 147 (59%) (p=0.003). The annualised exacerbation rate was 1.45 events per patient-year in the simvastatin group and 1.9 events per patient-year in the placebo group (incidence rate ratio 0.77, 95% CI 0.60-0.99). We found no effect on quality of life, lung function, 6-min walk test and high-sensitivity C-reactive protein. More patients dropped out in the simvastatin group compared to the placebo group (39 versus 29). CONCLUSION: In our single-centre RCT, simvastatin at a dose of 40 mg daily significantly prolonged time to first COPD exacerbation and reduced exacerbation rate.

Results of the Austrian National Lung Cancer Audit.

OBJECTIVES: The Austrian Lung Cancer Audit (ALCA) is a pilot study to evaluate clinical and organizational factors related to lung cancer care across Austria. MATERIALS AND METHODS: The ALCA is a prospective, observational, noninterventional cohort study conducted in 17 departments in Austria between September 2013 and March 2015. Participating departments were selected based on an annual case load of >50 patients with lung cancer. RESULTS: The ALCA included 745 patients, representing 50.5% of all newly diagnosed cancer cases during that time period. In 75.8% of patients, diagnosis was based on histology, and in 24.2% on cytology; 83.1% had non-small-cell lung cancer, 16.9% small-cell lung cancer; and only 4.6% had to be classified as not otherwise specified cancers. The median time elapsed between first presentation at hospital and diagnosis was 8 days (interquartile range [IQR]: 4-15; range: 0-132); between diagnosis and start of treatment it was 15 days for chemotherapy (IQR: 9-27; range: 0-83), 21 days (IQR: 10-35; range: 0-69) for radiotherapy, and 24 days (IQR: 11-36; range: 0-138) for surgery, respectively. In 150 patients undergoing surgical treatment, only 3 (2.0%; n = 147, 3 missings) were seen with postoperative restaging indicating unjustified surgery. One-year follow-up data were available for 723 patients, indicating excellent 49.8% survival; however, a wide range of survival between departments (range: 37.8-66.7) was seen. CONCLUSIONS: The ALCA conducted in high case load departments indicated management of lung cancer in accordance with international guidelines, and overall excellent 1-year survival.

Management of patients with SARS-CoV-2 infections and of patients with chronic lung diseases during the COVID-19 pandemic (as of 9 May 2020) : Statement of the Austrian Society of Pneumology (ASP).

The coronavirus disease 2019 (COVID-19) pandemic is currently a challenge worldwide. In Austria, a crisis within the healthcare system has so far been prevented. The treatment of patients with community-acquired pneumonia (CAP), including SARS-CoV­2 infections, should continue to be based on evidence-based CAP guidelines during the pandemic; however, COVID-19 specific adjustments are useful. The treatment of patients with chronic lung diseases has to be adapted during the pandemic but must still be guaranteed.

Treatment of Seizures in Children and Adults in the Emergency Medical System of the City of Zurich, Switzerland - Midazolam vs. Diazepam - A Retrospective Analysis.

INTRODUCTION: Seizures count to critical situations emergency medical systems (EMS) are confronted with. OBJECTIVES: Evaluation of a modified treatment algorithm (MTAS-EMS) using diazepam and midazolam due to a supply bottleneck of iv lorazepam in 2012. METHODS: Retrospective study where data from patients treated for seizures by the EMS of the city of Zurich were analyzed. Effectiveness of the MTAS-EMS and i.v. diazepam in children and adults was compared with respect of cessation of seizure without recurrence over the period until arrival at the hospital. The chi-square and Fisher's exact test were used to compare categorical data. The Student's t-test and Mann Whitney test were used to compare numerical data. p-values < 0.05 are considered significant. RESULTS: Of 584 documented missions, 165 treated patients (126 adults and 39 children) were included. 115 patients (80 adults and 35 children) were treated according the MTAS-EMS. Cessation of seizure was achieved in 85% of the adults and in 97% of the children, if all options of the MTAS-EMS were used. The first dose of nasal midazolam was more successful in children compared to adults (p = 0.012). In adults, the single dose of i.v. diazepam terminated the seizure in 98% (p = 0.001) compared to 57% for the single dose of iv and 64% for nasal midazolam. CONCLUSIONS: The treatment success of the MTAS-EMS is high. However, in adults the single dose of i.v. diazepam is as successful as the completely used MTAS-EMS and seems to be superior to the single dose iv and nasal midazolam.

Cell-Free Plasma DNA-Guided Treatment With Osimertinib in Patients With Advanced EGFR-Mutated NSCLC.

INTRODUCTION: Osimertinib is standard treatment for patients with advanced EGFR T790M-mutated non-small-cell lung cancer who have been pre-treated with EGFR-tyrosine kinase inhibitors (TKIs). We studied whether cell-free plasma DNA for T790M detection can be used to select patients for osimertinib treatment in the clinical routine. METHODS: From April 2015 to November 2016, we included 119 patients with advanced EGFR-mutated non-small-cell lung cancer who had progressed under treatment with an EGFR-TKI. The T790M mutation status was assessed in cell-free plasma DNA by droplet digital polymerase chain reaction in all patients and by tissue analyses in selected patients. RESULTS: T790M mutations were detected in 85 (93%) patients by analyses of cell-free plasma DNA and in 6 (7%) plasma-negative patients by tumor re-biopsy. Eighty-nine of 91 T790M-positive patients received osimertinib. Median progression-free survival (PFS) was 10.1 months (95% confidence interval [CI]: 8.1-12.1). Median survival was not reached and the 1-year survival was 64%. The response rate was 70% in T790M-positive patients (n = 91) in the intention-to-treat population. PFS trended to be shorter in patients with high T790M copy number (≥10 copies/mL) compared to those with low T790M copy number (<10 copies/mL) (hazard ratio for PFS = 1.72, 95% CI: 0.92-3.2, p = 0.09). A comparable trend was observed for overall survival (hazard ratio for overall survival = 2.16, 95% CI: 0.89-5.25, p = 0.09). No difference in response rate was observed based on T790M copy numbers. CONCLUSION: Plasma genotyping using digital polymerase chain reaction is clinically useful for the selection of patients who had progressed during first-line EGFR-TKI therapy for treatment with osimertinib.

Serum bile acids in patients with hepatopulmonary syndrome.

Background Hepatopulmonary syndrome (HPS) occurs in 20 - 30 % of patients with cirrhosis and is associated with increased mortality. Cholestasis and accumulation of bile acids (BAs) play a major role in chronic liver disease. Aim We aimed to evaluate the clinical role of serum BAs in patients with HPS. Methods Seventy-four patients with cirrhosis were included in this prospective study. Marker for cholestasis as total and individual serum BAs, bilirubin, alkaline phosphatase (AP), and gamma-glutamyl transpeptidase (GGT) were analyzed in patients screened for HPS. Criteria of HPS were fulfilled in 26 patients (35 %). Results In contrast to AP and GGT, bilirubin and serum BAs were significantly elevated in patients with HPS (median total BAs in HPS 83.5 µmol/L, IQR 43.1 - 148.9 vs. no HPS 26.9 µmol/L, 11 - 75.6; p < 0.001). Total BAs correlated with gas exchange by means of PaO2 / AaPO2 (r: -0.28, p < 0.05; r: 0.24, p < 0.05) and portal pressure (r: 0.33, p < 0.05). BAs were associated with HPS independently severity of underlying liver disease (OR: 1.012, 95 % CI: 1.001 - 1.023, p < 0.05). Conclusion BA retention is associated with HPS and gas exchange abnormalities. Future studies should assess whether modulation of BAs signaling may impact the course of HPS.

Canine scent detection for the diagnosis of lung cancer in a screening-like situation.

The prognosis in lung cancer depends largely on early stage detection, and thus new screening methods are attracting increasing attention. Canine scent detection has shown promising results in lung cancer detection, but there has only been one previous study that reproduces a screening-like situation. Here breath samples were collected from 122 patients at risk for lung cancer (smokers and ex-smokers); 29 of the subjects had confirmed diagnosis of lung cancer but had not yet been treated and 93 subjects had no signs or symptoms of lung cancer at the time of inclusion. The breath samples were presented to a trained sniffer dog squadron in a double-blind manner. A rigid scientific protocol was used with respect to earlier canine scent detection studies, with one difference: instead of offering one in five positive samples to the dogs, we offered a random number of positive samples (zero to five). The final positive and negative predictive values of 30.9% and 84.0%, respectively, were rather low compared to other studies. The results differed from those of previous studies, indicating that canine scent detection might not be as powerful as is looked for in real screening situations. One main reason for the rather poor performance in our setting might be the higher stress from the lack of positive responses for dogs and handlers.

[Non-invasive and invasive out of hospital ventilation in chronic respiratory failure : Consensus report of the working group on ventilation and intensive care medicine of the Austrian Society of Pneumology]. / Nichtinvasive und invasive außerklinische Beatmung beim chronisch respiratorischen Versagen : Konsensus-Report des Arbeitskreises für Beatmung & Intensivmedizin der Österreichischen Gesellschaft für Pneumologie.

The current consensus report was compiled under the patronage of the Austrian Society of Pneumology (Österreichischen Gesellschaft für Pneumologie, ÖGP) with the intention of providing practical guidelines for out-of-hospital ventilation that are in accordance with specific Austrian framework parameters and legal foundations. The guidelines are oriented toward a 2004 consensus ÖGP recommendation concerning the setup of long-term ventilated patients and the 2010 German Respiratory Society S2 guidelines on noninvasive and invasive ventilation of chronic respiratory insufficiency, adapted to national experiences and updated according to recent literature. In 11 chapters, the initiation, adjustment, and monitoring of out-of-hospital ventilation is described, as is the technical equipment and airway access. Additionally, the different indications-such as chronic obstructive pulmonary diseases, thoracic restrictive and neuromuscular diseases, obesity hypoventilation syndrome, and pediatric diseases-are discussed. Furthermore, the respiratory physiotherapy of adults and children on invasive and noninvasive long-term ventilation is addressed in detail.

Intraoperative ventilation strategy during cardiopulmonary bypass attenuates the release of matrix metalloproteinases and improves oxygenation.

BACKGROUND: Patients undergoing open heart surgery with cardiopulmonary bypass (CPB) often develop a systemic immune reaction, characterized by an increase of proinflammatory and anti-inflammatory mediators. We previously demonstrated that continued mechanical ventilation during CPB reduces this response. We hypothesized that this strategy may also impact on matrix metalloproteinase (MMP) release. MATERIAL AND METHODS: Thirty consecutive patients undergoing coronary artery bypass grafting with CPB were randomized into a ventilated (VG) (n = 15) and a standard non-ventilated group (NVG) (n = 15). Blood was collected at the beginning, at the end of surgery, and on the five consecutive days. MMPs, tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), and lipocalin 2 (LCN2) were measured by enzyme-linked immunosorbent assay. Parameters of transpulmonary oxygen transport were assessed at different time points. RESULTS: MMP-8, MMP-9, and LCN2 were significantly lower at the end of surgery in VG compared with those in NVG patients (MMP-8 [ng/mL]: 7.1 [3.5] versus 12.5 [7.7], P = 0.02; MMP-9 [ng/mL]: 108 [42] versus 171 [98], P = 0.029; LCN2 [ng/mL]: 109 [42] versus 171 [98], P = 0.03). TIMP-1 concentrations were lower on postoperative day one, (TIMP-1 [ng/mL]: 174 [55] versus 273 [104], P = 0.003), whereas MMP-3 levels were lower on postoperative days four and five (MMP-3 [ng/mL]: 44 [17] versus 67 [35], P = 0.026). The arterial partial pressure of oxygen/fraction of inspired oxygen ratio was significantly higher in VG patients throughout the postoperative observation period, which did not affect the length of postoperative ventilatory support. CONCLUSIONS: Continued mechanical ventilation during CPB reduces serum levels of MMPs, their inhibitor TIMP-1 and LCN2, which preserves MMP-9 activity. The present study suggests that continued mechanical ventilation improves postoperative oxygenation and could potentially prevent aggravation of lung injury after CPB.

Von Willebrand factor antigen for detection of hepatopulmonary syndrome in patients with cirrhosis.

BACKGROUND & AIMS: Hepatopulmonary syndrome (HPS) occurs in 20-30% of patients with liver cirrhosis and is associated with a >2 fold increased mortality. Endothelial dysfunction seems to play a central role in its pathogenesis. von Willebrand factor antigen (vWF-Ag), an established marker of endothelial dysfunction, is significantly elevated in patients with liver cirrhosis, portal hypertension, and in experimental HPS. Aim of the present study was to evaluate the impact of vWF-Ag as a screening marker for presence of HPS in patients with stable cirrhosis. METHODS: 145 patients with stable liver cirrhosis were screened for presence of HPS in this prospective cohort type cross sectional diagnostic study. vWF-Ag and SaO2 levels were assessed at time of screening for HPS. Criteria of HPS were fulfilled in 31 (21%) patients. RESULTS: vWF-Ag levels were significantly higher in patients with HPS compared to patients without HPS (p<0.001). Furthermore, vWF-Ag correlated significantly with gas exchange in HPS positive patients (p<0.05). vWF-Ag is an independent predictor of HPS after correction for sex, age, model for endstage-liver disease (MELD), and hepatic venous pressure gradient (HVPG) (OR per 1% increase of vWF-Ag: 1.02, 95% CI: 1.00-1.04, p<0.05). The best cut-off was 328% at a sensitivity of 100% and specificity of 53.5%; positive predictive value: 36.9%; negative predictive value: 100%. CONCLUSIONS: HPS is associated with elevated vWF-Ag levels. vWF-Ag may be a useful screening tool for early detection of HPS. Further studies investigating vWF-Ag in HPS will be needed to confirm our findings.

Pharmacokinetics of ganciclovir during continuous venovenous hemodiafiltration in critically ill patients.

Ganciclovir is an antiviral agent that is frequently used in critically ill patients with cytomegalovirus (CMV) infections. Continuous venovenous hemodiafiltration (CVVHDF) is a common extracorporeal renal replacement therapy in intensive care unit patients. The aim of this study was to investigate the pharmacokinetics of ganciclovir in anuric patients undergoing CVVHDF. Population pharmacokinetic analysis was performed for nine critically ill patients with proven or suspected CMV infection who were undergoing CVVHDF. All patients received a single dose of ganciclovir at 5 mg/kg of body weight intravenously. Serum and ultradiafiltrate concentrations were assessed by high-performance liquid chromatography, and these data were used for pharmacokinetic analysis. Mean peak and trough prefilter ganciclovir concentrations were 11.8 ± 3.5 mg/liter and 2.4 ± 0.7 mg/liter, respectively. The pharmacokinetic parameters elimination half-life (24.2 ± 7.6 h), volume of distribution (81.2 ± 38.3 liters), sieving coefficient (0.76 ± 0.1), total clearance (2.7 ± 1.2 liters/h), and clearance of CVVHDF (1.5 ± 0.2 liters/h) were determined. Based on population pharmacokinetic simulations with respect to a target area under the curve (AUC) of 50 mg · h/liter and a trough level of 2 mg/liter, a ganciclovir dose of 2.5 mg/kg once daily seems to be adequate for anuric critically ill patients during CVVHDF.

MUNDUS project: MUltimodal neuroprosthesis for daily upper limb support.

BACKGROUND: MUNDUS is an assistive framework for recovering direct interaction capability of severely motor impaired people based on arm reaching and hand functions. It aims at achieving personalization, modularity and maximization of the user's direct involvement in assistive systems. To this, MUNDUS exploits any residual control of the end-user and can be adapted to the level of severity or to the progression of the disease allowing the user to voluntarily interact with the environment. MUNDUS target pathologies are high-level spinal cord injury (SCI) and neurodegenerative and genetic neuromuscular diseases, such as amyotrophic lateral sclerosis, Friedreich ataxia, and multiple sclerosis (MS). The system can be alternatively driven by residual voluntary muscular activation, head/eye motion, and brain signals. MUNDUS modularly combines an antigravity lightweight and non-cumbersome exoskeleton, closed-loop controlled Neuromuscular Electrical Stimulation for arm and hand motion, and potentially a motorized hand orthosis, for grasping interactive objects. METHODS: The definition of the requirements and of the interaction tasks were designed by a focus group with experts and a questionnaire with 36 potential end-users. RESULTS: The functionality of all modules has been successfully demonstrated. User's intention was detected with a 100% success. Averaging all subjects and tasks, the minimum evaluation score obtained was 1.13 ± 0.99 for the release of the handle during the drinking task, whilst all the other sub-actions achieved a mean value above 1.6. All users, but one, subjectively perceived the usefulness of the assistance and could easily control the system. Donning time ranged from 6 to 65 minutes, scaled on the configuration complexity. CONCLUSIONS: The MUNDUS platform provides functional assistance to daily life activities; the modules integration depends on the user's need, the functionality of the system have been demonstrated for all the possible configurations, and preliminary assessment of usability and acceptance is promising.

Unmeasured anions are associated with short-term mortality in patients with hypoxic hepatitis.

OBJECTIVE: Hypoxic hepatitis is a common cause of hepatic impairment in critically ill patients and is an independent risk factor for mortality. An elevated level of unmeasured anions is another unfavourable prognostic marker in many disease entities. While the biochemical nature of unmeasured anions is unknown, data suggest that they may be released from the liver. Therefore, the purpose of this study was to determine whether the strong ion gap-the gold standard for estimation of unmeasured anions-is elevated and associated with outcome in patients with hypoxic hepatitis. METHODS: One hundred and five consecutive patients with hypoxic hepatitis admitted to the (intensive care unit) ICU of a university hospital were prospectively included in the study and compared with 15 healthy controls. RESULTS: Compared with the controls, patients with hypoxic hepatitis had an elevated strong ion gap (4.0 ± 2.6 vs. 7.8 ± 4.0 mmol/L; p = 0.0002) that contributed to metabolic acidosis. Patients dying within 5 days had a larger strong ion gap upon admission than did patients surviving beyond 5 days. The mean strong ion gap (SIG) over the course of the first 5 days after admission to the ICU was 1.3 mmol/L (0.3-2.3 mmol/L) larger in patients who died compared with patients who survived, p = 0.008. In multivariate Cox-regression, larger strong ion gaps were associated with shorter survival time. The SIG correlated positively with both AST and ALT. CONCLUSIONS: Unmeasured anions are elevated in patients with hypoxic hepatitis, contribute to metabolic acidosis and are associated with mortality. The liver is a possible source of the unmeasured anions, which may represent markers of tissue damage in hypoxic hepatitis.

Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes.

Macrophages play a key role in responding to pathogens and initiate an inflammatory response to combat microbe multiplication. Deactivation of macrophages facilitates resolution of the inflammatory response. Deactivated macrophages are characterized by an immunosuppressive phenotype, but the lack of unique markers that can reliably identify these cells explains the poorly defined biological role of this macrophage subset. We identified lipocalin 2 (LCN2) as both a marker of deactivated macrophages and a macrophage deactivator. We show that LCN2 attenuated the early inflammatory response and impaired bacterial clearance, leading to impaired survival of mice suffering from pneumococcal pneumonia. LCN2 induced IL-10 formation by macrophages, skewing macrophage polarization in a STAT3-dependent manner. Pulmonary LCN2 levels were tremendously elevated during bacterial pneumonia in humans, and high LCN2 levels were indicative of a detrimental outcome from pneumonia with Gram-positive bacteria. Our data emphasize the importance of macrophage deactivation for the outcome of pneumococcal infections and highlight the role of LCN2 and IL-10 as determinants of macrophage performance in the respiratory tract.

Storage of bronchoalveolar lavage fluid and accuracy of microbiologic diagnostics in the ICU: a prospective observational study.

INTRODUCTION: Early initiation of appropriate antimicrobial treatment is a cornerstone in managing pneumonia. Because microbiologic processing may not be available around the clock, optimal storage of specimens is essential for accurate microbiologic identification of pathogenetic bacteria. The aim of our study was to determine the accuracy of two commonly used storage approaches for delayed processing of bronchoalveolar lavage in critically ill patients with suspected pneumonia. METHODS: This study included 132 patients with clinically suspected pneumonia at two medical intensive care units of a tertiary care hospital. Bronchoalveolar lavage samples were obtained and divided into three aliquots: one was used for immediate culture, and two, for delayed culture (DC) after storage for 24 hours at 4°C (DC4) and -80°C (DC-80), respectively. RESULTS: Of 259 bronchoalveolar lavage samples, 84 (32.4%) were positive after immediate culture with 115 relevant culture counts (≥104 colony-forming units/ml). Reduced (<104 colony-forming units/ml) or no growth of four and 57 of these isolates was observed in DC4 and DC-80, respectively. The difference between mean bias of immediate culture and DC4 (-0.035; limits of agreement, -0.977 to 0.906) and immediate culture and DC-80 (-1.832; limits of agreement, -4.914 to 1.267) was -1.788 ± 1.682 (P < 0.0001). Sensitivity and negative predictive value were 96.5% and 97.8% for DC4 and 50.4% and 75.4% for DC-80, respectively; the differences were statistically significant (P < 0.0001). CONCLUSIONS: Bronchoalveolar lavage samples can be processed for culture when stored up to 24 hours at 4°C without loss of diagnostic accuracy. Delayed culturing after storage at -80°C may not be reliable, in particular with regard to Gram-negative bacteria.

Health-related quality of life of long-term survivors of intensive care: changes after intensive care treatment. Experience of an Austrian intensive care unit.

OBJECTIVE: The aim of the study was to determine if health-related quality of life of long-term survivors changes 24 months after intensive care treatment compared to the quality of life before admission. METHODS: From 281 patients treated at the ICU in 2001, 132 survivors were contacted by phone on average 24 months after discharge. Fernandez questionnaire was used to assess preadmission quality of life prospectively and postdischarge quality of life, retrospectively. In addition, age, sex, admission diagnosis, ICU length of stay, presence of organ failure, and necessity of mechanical ventilation were determined. RESULTS: In the 101 ICU survivors who responded to the questionnaire, the total score of quality of life did not change significantly over time (5.48 ± 5.3 before admission vs. 5.6 ± 5.8 at follow-up; p = 0.9). Similarly, the performance of normal daily activities did not alter (3.0 ± 3.5 vs. 3.39 ± 3.6; p = 0,3). In contrast, the ability to perform basic physiological activities worsened significantly (0.39 ± 0.76 vs. 0.76 ± 1.52; p = 0.037), whereas the emotional state improved significantly after intensive care treatment (2.08 ± 1.78 vs. 1.46 ± 1.56, p = 0.003). In a stepwise multiple regression analysis the total score of quality of life before admission was the only variable which influenced the quality of life 2 years after ICU-stay. CONCLUSIONS: In the interviewed population the total score of health-related quality of life did not change after intensive care treatment. Surprisingly, emotional state improved significantly although physical performance decreased. Quality of life after ICU discharge was predominantly influenced by preadmission quality of life. However, these results are not reflective of all ICU survivors.

Pretreatment serum C-reactive protein levels predict benefit from multimodality treatment including radical surgery in malignant pleural mesothelioma: a retrospective multicenter analysis.

OBJECTIVE: To evaluate the prognostic and predictive relevance of pretreatment serum C-reactive protein (CRP) in malignant pleural mesothelioma (MPM) patients. BACKGROUND: MPM is a rare but aggressive disease with poor treatment outcome. Therapeutic decision is challenging, and predictive biomarkers for better treatment stratification are urgently needed. METHODS: Clinical data, including survival and pretreatment CRP levels, were retrospectively collected from 115 patients with histologically proven MPM. Patients with any evidence for infectious disease were excluded. The association between CRP levels and survival was analyzed using Cox models adjusted for clinical and pathological factors. RESULTS: Median pretreatment CRP of all patients was 1.19 mg/dL (range: 0.00-22.62 mg/dL). Patients with elevated CRP levels (≥1 mg/dL; n = 62, 53.9%) had a significantly shorter overall survival compared with those with normal CRP (hazard ratio [HR] 2.81, 95% confidence interval [CI] 1.82-4.33; P < 0.001). In multivariate survival analyses, elevated CRP was confirmed as an independent prognostic factor in MPM (HR 2.07, 95% CI 1.23-3.46; P = 0.01). Most interestingly, we observed a significant interaction between CRP and treatment modality (P < 0.001). Among patients with normal CRP levels, radical tumor resection within multimodality therapy was associated with distinctly prolonged overall survival when compared with treatment protocols without surgery (HR 7.26, 95% CI 3.40-15.49; P < 0.001). In contrast among patients with elevated CRP, no survival benefit was achieved by radical surgery within multimodality approaches (HR 0.911, 95% CI 0.53-1.58; P = 0.74). CONCLUSIONS: Our results suggest that multimodality regimens including radical resection increase survival selectively in MPM patients with normal pretreatment serum CRP levels.

Increased serum levels of HSP27 as a marker for incipient chronic obstructive pulmonary disease in young smokers.

BACKGROUND: Although chronic obstructive pulmonary disease (COPD) is amongst the leading causes of morbidity and mortality, no biomarkers for its early detection are known. We have recently demonstrated that COPD is accompanied by elevated serum heat shock protein (HSP) 27 levels as compared to a control population. OBJECTIVES: In an open prospective study, we investigated whether elevated HSP27 levels are associated with the early radiological signs of COPD, i.e., air trapping (AT), emphysema (E) and impaired lung function. METHODS: In total, 120 apparently healthy smokers underwent lung function testing and serum sampling. Serum levels of HSP27, phospho-HSP27, CXCR2 chemokines and proteins related to inflammation, tissue remodeling and apoptosis were evaluated by ELISA. Of these 120 subjects, 94 voluntarily underwent a high-resolution computed tomography scan. RESULTS: AT or AT and E were detected in 57.45%. Subjects with AT and E (n = 23) showed significantly higher HSP27 levels than those without any pathology [i.e., nothing abnormal detected (NAD)] (4,618 +/- 1,677 vs. 3,282 +/- 1,607 pg/ml; p = 0.0081). In a univariate logistic regression model including NAD and AT and E, the area under the curve of HSP27 in the receiver-operating-characteristic curve was 0.724, (0.594­0.854, 95% CI; p = 0.0033). Interestingly, proinflammatory IL-8 was elevated in those subjects with evidence of AT and E compared to those with AT and NAD. Lung function did not correlate with increased HSP27 levels or pathological radiological findings. CONCLUSIONS: HSP27 serum levels correlated with the early radiological signs of COPD, whereas lung function did not match with radiological findings or HSP27 serum levels. Serum HSP27 levels may serve as a potential marker to identify the early signs of COPD independent of lung function in young smokers.

Impact of hypoxic hepatitis on mortality in the intensive care unit.

PURPOSE: Hypoxic hepatitis (HH) is a form of hepatic injury following arterial hypoxemia, ischemia, and passive congestion of the liver. We investigated the incidence and the prognostic implications of HH in the medical intensive care unit (ICU). METHODS: A total of 1,066 consecutive ICU admissions at three medical ICUs of a university hospital were included in this prospective cohort study. All patients were screened prospectively for the presence of HH according to established criteria. Independent risk factors of mortality in this cohort of critically ill patients were identified by a multivariate Poisson regression model. RESULTS: A total of 118 admissions (11%) had HH during their ICU stay. These patients had different baseline characteristics, longer median ICU stay (8 vs. 6 days, p < 0.001), and decreased ICU survival (43 vs. 83%, p < 0.001). The crude mortality rate ratio of admissions with HH was 4.62 (95% CI 3.63-5.86, p < 0.001). Regression analysis demonstrated strong mortality risk for admissions with HH requiring vasopressor therapy (adjusted rate ratio 4.91; 95% CI 2.51-9.60, p < 0.001), whereas HH was not significantly associated with mortality in admissions without vasopressor therapy (adjusted rate ratio 1.79, 95% CI 0.52-6.23, p = 0.359). CONCLUSIONS: Hypoxic hepatitis (HH) occurs frequently in the medical ICU. The presence of HH is a strong risk factor for mortality in the ICU in patients requiring vasopressor therapy.