Net reclassification improvement with serial biomarkers and bed-sided spirometry to early predict the need of organ support during the early post-transplantation in-hospital stay in allogeneic HCT recipients.

To predict the need of intensive care unit admission with organ support during the transplantation hospital stay in 101 consecutives allogeneic hematopoietic cell transplantation (allo-HCT) recipients the added predictive utility of three times per week Copeptin, MR-proADM, MR-proANP, NT-proBNP, IL-6, Procalcitonin, D-dimer and three times per week bed-sided pulmonary function test was determined in comparison with an index model. The index model was calculated by multivariate regression analysis out of the patients' routine laboratory parameters. To calculate the added predictive utility of the investigated markers the Δ-AUC and the continuous net reclassification improvement (cNRI + 2 to - 2), splitted for events and non-events were calculated for each marker in comparison with the index model. According to the Δ-AUC, none of the parameters improved risk prediction. In contrast, the cNRI was significantly improved for events and non-events by Copeptin (event 0.75, p value 0.0013; non-event 0.4, p value 0.000079) and for events by NT-proBNP (0.6, p value 0.018). D-dimer and PCT significantly predicted the non-event. Of the spirometry parameters, the FEF50% improved prediction of event and non-event according to the cNRI model. Our data support the additional serial analysis of Copeptin and NT-proBNP in allo-HCT recipients during the transplantation hospital stay.

[Epidemiology, Diagnosis and Treatment of Adult Patients with Nosocomial Pneumonia - Update 2017 - S3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy, the German Radiological Society and the Society for Virology]. / Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie ­ Update 2017.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However, infections on general wards are increasing. A central issue are infections with multidrug resistant (MDR) pathogens which are difficult to treat in the empirical setting potentially leading to inappropriate use of antimicrobial therapy.This guideline update was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and treatment of HAP on the basis of quality of evidence and benefit/risk ratio.This guideline has two parts. First an update on epidemiology, spectrum of pathogens and antimicrobials is provided. In the second part recommendations for the management of diagnosis and treatment are given. New recommendations with respect to imaging, diagnosis of nosocomial viral pneumonia and prolonged infusion of antibacterial drugs have been added. The statements to risk factors for infections with MDR pathogens and recommendations for monotherapy vs combination therapy have been actualised. The importance of structured deescalation concepts and limitation of treatment duration is emphasized.

Clinical Relevance of Computed Tomography Pulmonary Venography.

BACKGROUND: In clinical routine, the pulmonary contrast-enhanced chest computer tomography (CT) is usually focussed on the pulmonary arteries. The purpose of this pictorial essay is to raise the clinicians' awareness for the clinical relevance of CT pulmonary venography. CASE PRESENTATION: A pictorial case series illustrates the clinical consequences of different pulmonary venous pathologies on systemic, pulmonary and bronchial circulation. CONCLUSION: Computed tomography pulmonary venography must be considered before atrial septal defect (ASD) closure and pulmonary lobectomy. Computed tomography pulmonary venography should be considered for patients with right ventricular overload and pulmonary hypertension, as well as for patients with unclear recurrent pulmonary infections, progressive dyspnoea, pleural effusions, haemoptysis, and for patients with respiratory distress after lung-transplantation.

[Management of Adult Community-acquired Pneumonia and Prevention - Update 2016]. / Behandlung von erwachsenen Patienten mit ambulant erworbener Pneumonie und Prävention - Update 2016.

The present guideline provides a new and updated concept of treatment and prevention of adult patients with community-acquired pneumonia. It replaces the previous guideline dating from 2009.The guideline was worked out and agreed on following the standards of methodology of a S3-guideline. This includes a systematic literature search and grading, a structured discussion of recommendations supported by the literature as well as the declaration and assessment of potential conflicts of interests.The guideline has a focus on specific clinical circumstances, an update on severity assessment, and includes recommendations for an individualized selection of antimicrobial treatment as well as primary and secondary prevention.

Tolerated sting challenge in patients on Hymenoptera venom immunotherapy improves health-related quality of life.

BACKGROUND: Sting challenge with a live insect remains the best test for proving the efficacy of immunotherapy in Hymenoptera allergy. OBJECTIVE: We studied the impact of tolerated sting challenge on quality of life. PATIENTS AND METHODS: In this prospective study, data were collected via self-report questionnaires completed by consenting patients with Hymenoptera venom allergy on venom immunotherapy before and after a sting challenge. RESULTS: The study population comprised 100 adult patients (82 with yellow jacket allergy and 18 with honeybee allergy) who participated between September 2009 and November 2010. After the sting challenge, the score on the Vespid Allergy Quality of Life Questionnaire revealed a statistically significant improvement (mean [SD] change, 0.73 [0.98]; P < .0001; 95% CI, 0.52-0.94). This improvement was independent of the patients' gender and age and the severity of the initial anaphylactic reaction. A statistically significant improvement was documented in 2 subgroups of the Short Form 36 Health Survey (physical functioning, mean change, -5.78 [25.23]; P = .038; 95% CI, -11.22 to -0.34; vitality, mean change -4.29 [12.49]; P =.002; 95% CI, -7.02 to -1.57). CONCLUSIONS: Sting challenge results in a significant improvement in disease-specific quality of life and subgroups of general quality of life in patients allergic to Hymenoptera venom receiving established venom immunotherapy.

Tolerated sting challenge in patients on hymenoptera venom immunotherapy improves health-related quality of life

Background: Sting challenge with a live insect remains the best test for proving the efficacy of immunotherapy in Hymenoptera allergy. Objective: We studied the impact of tolerated sting challenge on quality of life. Patients and Methods: In this prospective study, data were collected via self-report questionnaires completed by consenting patients with Hymenoptera venom allergy on venom immunotherapy before and after a sting challenge. Results: The study population comprised 100 adult patients (82 with yellow jacket allergy and 18 with honeybee allergy) who participated between September 2009 and November 2010. After the sting challenge, the score on the Vespid Allergy Quality of Life Questionnaire revealed a statistically significant improvement (mean [SD] change, 0.73 [0.98]; P <.0001; 95% CI, 0.52-0.94). This improvement was independent of the patients' gender and age and the severity of the initial anaphylactic reaction. A statistically significant improvement was documented in 2 subgroups of the Short Form 36 Health Survey (physical functioning, mean change, -5.78 [25.23]; P =.038; 95%CI, -11.22 to -0.34; vitality, mean change -4.29 [12.49]; P =.002; 95% CI, -7.02 to -1.57). Conclusions: Sting challenge results in a significant improvement in disease-specific quality of life and subgroups of general quality of life in patients allergic to Hymenoptera venom receiving established venom immunotherapy (AU)

Antecedentes: La prueba de repicadura con insecto vivo continúa siendo la exploración más adecuada para determinar la eficacia de la inmunoterapia en la alergia a himenópteros. Objetivo: Estudiar el impacto que produce sobre la calidad de vida relacionada con la salud, una prueba de repicadura bien tolerada. Métodos: Se trata de un estudio prospectivo, en el que una muestra consecutiva de pacientes alérgicos a himenópteros y en tratamiento con inmunoterapia, respondieron un conjunto de cuestionarios auto-administrados antes y después de la prueba de repicadura. Resultados: Un total de cien pacientes con alergia a himenópteros (82 avispa y 18 abeja) participaron en el estudio, que se realizó entre septiembre del 2009 y noviembre del 2010. La puntuación del cuestionario VQLQ mejoró de forma significativa tras la prueba de repicadura (media del cambio 0.73, SD 0.98, p < 0.0001, 95% IC: 0.52-0.94). Esta mejoría era independiente del sexo, edad o de la gravedad de la reacción anafiláctica inicial por la que se instauró el tratamiento. También se observó una mejoría significativa en dos de los dominios del cuestionario genérico SF 36 (función física, media del cambio -5.78, SD 25.23, p = 0.038, 95% IC: -11.22- -0.34; vitalidad, media del cambio -4.29, SD 12.49, p = 0.002, 95% IC: -7.02- -1.57). Conclusiones: La prueba de repicadura bien tolerada se asoció a un incremento de la calidad de vida de los pacientes con alergia a himenópteros, y en tratamiento con inmunoterapia. La mejoría se documentó tanto por un cuestionario específico para la enfermedad (VQLQ) como en algunos dominios del cuestionario genérico SF-36 (AU)

Potential clinical predictors of outcome after postoperative radiotherapy of non-small cell lung cancer.

AIM: The aim of this analysis was to investigate the impact of tumour-, treatment- and patient-related cofactors on local control and survival after postoperative adjuvant radiotherapy in patients with non-small cell lung cancer (NSCLC), with special focus on waiting and overall treatment times. PATIENTS AND METHODS: For 100 NSCLC patients who had received postoperative radiotherapy, overall, relapse-free and metastases-free survival was retrospectively analysed using Kaplan-Meier methods. The impact of tumour-, treatment- and patient-related cofactors on treatment outcome was evaluated in uni- and multivariate Cox regression analysis. RESULTS: No statistically significant difference between the survival curves of the groups with a short versus a long time interval between surgery and radiotherapy could be shown in uni- or multivariate analysis. Multivariate analysis revealed a significant decrease in overall survival times for patients with prolonged overall radiotherapy treatment times exceeding 42 days (16 vs. 36 months) and for patients with radiation-induced pneumonitis (8 vs. 29 months). CONCLUSION: Radiation-induced pneumonitis and prolonged radiation treatment times significantly reduced overall survival after adjuvant radiotherapy in NSCLC patients. The negative impact of a longer radiotherapy treatment time could be shown for the first time in an adjuvant setting. The hypothesis of a negative impact of longer waiting times prior to commencement of adjuvant radiotherapy could not be confirmed.

[Informations and recommendations of the German Respiratory Society and the Paul-Ehrlich-Society for chemotherapy concerning the outbreak of influenza A(H7N9) virus infections in humans]. / Informationen und Empfehlungen der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. und der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. zum Ausbruch der Influenza A(H7N9)-Virus-Infektion beim Menschen.

In March 2013, the first cases of avian influenza virus infections in humans were reported by the authorities of the PR of China to the World Health Organization. This influenza A(H7N9) virus comprises genes of at least four different avian influenza viruses, some segments mimicking human-like influenza-signatures. Until 11 August, 2013 135 humans were infected, 44 (33%) died. The clinical course is characterized by fever, cough, gastrointestinal symptoms, lympho- and thrombopenia as well by the rapid onset of an acute respiratory distress syndrome in nearly 25% of the cases. Although human to human transmission may have occurred only in the context of three clusters, strict hygiene measures should be instituted and any suspect case should be reported to the local health authorities immediately. The detection of influenza A(H7N9) is based on real-time polymerase chain reaction (PCR). Antiviral treatment should be initiated as early as possible for suspect, probable or confirmed cases, even when 48 hours have passed after symptom onset. At present the future development of this epidemic cannot be predicted.

Tolerability to etoricoxib in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: The use of selective cyclooxygenase (COX) 2 inhibitors as an alternative to aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been suggested for patients with aspirin-exacerbated respiratory disease (AERD). OBJECTIVE: To evaluate tolerability to etoricoxib, a second-generation COX-2 inhibitor with high in vitro selectivity for COX-2 in patients with AERD. METHODS: We conducted a retrospective review of patients with suspected aspirin intolerance seen between October 2007 and April 2012. Single-blind, placebo-controlled oral challenges with increasing doses of aspirin and etoricoxib were performed on 3 different days. RESULTS: Of 262 patients with suspected aspirin intolerance, 248 underwent challenge testing with aspirin and 122 (49.2%) showed positive test results. In 104 of these aspirin-sensitive patients, etoricoxib was tested as an alternative drug and was tolerated in all but 3 (2.9%), who developed a positive asthmatic reaction. CONCLUSIONS: The highly selective COX-2 inhibitor etoricoxib was tolerated in most but not all patients tested. An oral provocation test is therefore recommended before prescribing etoricoxib for patients with AERD.

Tolerability to Etoricoxib in Patients With Aspirin-Exacerbated Respiratory Disease

Introducción: El uso de inhibidores selectivos de la cicloxigenasa-2 (COX-2) como alternativa a la aspirina y otros analgésicos antiinflamatorios no-esteroideos (AINEs) puede ser una alternativa terapeútica para pacientes con enfermedad respiratoria exacerbada por aspirina (EREA). Objetivo: Evaluar la tolerancia a etericoxib, un inhibidor de segunda generación de la COX-2 con alta selectividad in vitro para COX-2, en pacientes con EREA. Para ello se realizó una revisión retrospectiva de pacientes con sospecha de intolerancia a aspirina vistos entre 10/2007 y 04/2012. Se realizaron pruebas de provocación oral controladas con dosis crecientes de aspirina y etericoxib en tres días diferentes. Resultados: De los 262 pacientes con sospecha de intolerancia a aspirina, 248 fueron sometidos a prueba de provocación con aspirina y 122 (49,2%) mostraron un resultado positivo. En 104 de estos, el etericoxib se testó como un medicamento alternativo y fue tolerado en todos, excepto en 3 pacientes (2,9%) que desarrollaron una reacción asmática. Conclusión: El etericoxib se toleró en la mayoría de los pacientes estudiados. Es recomendable una prueba de provocación antes de indicar este medicamento en el tratamiento de pacientes con EREA (AU)

Background: The use of selective cyclooxygenase (COX) 2 inhibitors as an alternative to aspirin and other nonsteroidal anti-inflamatory drugs (NSAIDs) has been suggested for patients with aspirin-exacerbated respiratory disease (AERD). Objective: To evaluate tolerability to etoricoxib, a second-generation COX-2 inhibitor with high in vitro selectivity for COX-2 in patients with AERD. Methods: We conducted a retrospective review of patients with suspected aspirin intolerance seen between October 2007 and April 2012. Single-blind, placebo-controlled oral challenges with increasing doses of aspirin and etoricoxib were performed on 3 different days. Results: Of 262 patients with suspected aspirin intolerance, 248 underwent challenge testing with aspirin and 122 (49.2%) showed positive test results. In 104 of these aspirin-sensitive patients, etoricoxib was tested as an alternative drug and was tolerated in all but 3 (2.9%), who developed a positive asthmatic reaction. Conclusions: The highly selective COX-2 inhibitor etoricoxib was tolerated in most but not all patients tested. An oral provocation test is therefore recommended before prescribing etoricoxib for patients with AERD (AU)

[Epidemiology, diagnosis and treatment of adult patients with nosocomial pneumonia. S-3 Guideline of the German Society for Anaesthesiology and Intensive Care Medicine, the German Society for Infectious Diseases, the German Society for Hygiene and Microbiology, the German Respiratory Society and the Paul-Ehrlich-Society for Chemotherapy]. / Epidemiologie, Diagnostik und Therapie erwachsener Patienten mit nosokomialer Pneumonie. S-3 Leitlinie der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e.V., der Deutschen Gesellschaft für Infektiologie e.V., der Deutschen Gesellschaft für Hygiene und Mikrobiologie e.V., der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. und der Paul-Ehrlich-Gesellschaft für Chemotherapie e.V.

Nosocomial pneumonia (HAP) is a frequent complication of hospital care. Most data are available on ventilator-associated pneumonia. However infections on general wards are also increasing. A central issue are infections with multi drug resistant (MDR) pathogens which are difficult to treat particularly in the empirical setting potentially leading to inappropriate use of antimicrobial therapy. This guideline was compiled by an interdisciplinary group on the basis of a systematic literature review. Recommendations are made according to GRADE giving guidance for the diagnosis and therapy of HAP on the basis of quality of evidence and benefit/risk ratio. The guideline has two parts. First an update on epidemiology, spectrum of pathogens and antiinfectives is provided. In the second part recommendations for the management of diagnosis and treatment are given. Proper microbiologic work up is emphasized for knowledge of the local patterns of microbiology and drug susceptibility. Moreover this is the optimal basis for deescalation in the individual patient. The intensity of antimicrobial therapy is guided by the risk of infections with MDR. Structured deescalation concepts and strict limitation of treatment duration should lead to reduced selection pressure.

[Update pneumonia 2012]. / Update Pneumonie 2012.

Pneumonia is an infection of the lung parenchyma and defined as combination of a novel radiological infiltrate with typical signs and symptoms. There are 3 distinguished entities of pneumonia: community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and pneumonia in the immunocompromised patient. The spectrum of pathogens is increasing from CAP, mostly caused by pneumococci, over HAP (additional multi-drug resistant pathogens) to pneumonia in the immunocompromised (additional opportunistic pathogens). Therefore, each entity demands a specific diagnostic and therapeutic approach. This review compares the 3 forms of pneumonia and presents a guideline based clinical approach in the context of current studies.

Copeptin predicts clinical deterioration and persistent instability in community-acquired pneumonia.

RATIONALE: Optimal risk prediction of early clinical deterioration in community-acquired pneumonia (CAP) remains unresolved. We prospectively examined the predictive value of the new biomarkers copeptin and proadrenomedullin (MR-proADM) in comparison to clinical scores and inflammatory markers to predict early high risk prognosis in CAP. METHODS: 51 consecutive hospitalised adult patients were enrolled. We measured CRB-65- and PSI-scores, the ATS/IDSA 2007 minor criteria to predict ICU-admission and the biomarkers CRP, procalcitonin, copeptin and MR-proADM on admission. Predefined outcome parameters were combined mortality or ICU-admission after 7 days and clinical instability after 72 h. RESULTS: Copeptin was the only biomarker significantly elevated in patients with either adverse short term outcome (p = 0.003). According to ROC-curve analysis, copeptin predicted ICU admission or death within 7 days (AUC 0.81, cut-off 35 pmol/l: sensitivity 78%, specificity 79%) and persistent clinical instability after 72 h (AUC 0.74). In Kaplan-Meier-analysis patients with high copeptin showed lower ICU-free survival within 7 days (p = 0.001). The diagnostic accuracy of copeptin was superior to the CRB-65 score and comparable to the PSI-score and the ATS/IDSA minor criteria. If copeptin was included as additional minor criterion for combined 7-day mortality or ICU-admission, the diagnostic accuracy of the minor criteria was significantly improved (p = 0.045). CONCLUSION: Copeptin predicts early deterioration and persistent clinical instability in hospitalised CAP and improves the predictive properties of existing clinical scores. It should be evaluated within a biomarker guided strategy for early identification of high risk CAP patients who most likely benefit from early intensified management strategies.

Respiratory failure in patients undergoing allogeneic hematopoietic SCT--a randomized trial on early non-invasive ventilation based on standard care hematology wards.

The prognosis of patients suffering from respiratory failure (RF) after allogeneic hematopoietic SCT (HSCT) is poor. However, early treatment for using non-invasive ventilation (NIV) may be of benefit. We conducted a randomized trial to prove the impact of early NIV in patients in the early post-transplant period. A total of 526 patients undergoing HSCT in a single center were monitored for signs of RF. Patients with RF were enrolled into either treatment arm A (oxygen supply only) or treatment arm B (oxygen+intermittent NIV). RF had to be diagnosed in 86 patients (16%). RF was an independent risk factor for both short-term (100 day mortality/ OR 2.76; P<0.001) and long-term survival (OR 1.57; P<0.01). Although early RF treatment with NIV was associated with a decreased rate of failure to achieve sufficient oxygenation (39% in arm A vs 24% in arm B, P=0.17), neither intensive care unit admission rate, nor need for intubation or survival parameters were affected by the treatment strategy. An early interventional strategy using NIV was not associated with improvement of the prognosis of the patients. The limited influence of NIV may be related to the study design allowing for switching of treatment in case of unsatisfactory efficacy.

Ambrisentan improves exercise capacity and symptoms in patients with portopulmonary hypertension.

INTRODUCTION: Ambrisentan, a selective endothelin receptor antagonist has been approved in several countries for pulmonary arterial hypertension. No data have been published on the efficacy of ambrisentan on improvement of exercise capacity in patients with portopulmonary hypertension (PoPH). PATIENTS AND METHODS: We retrospectively analyzed the safety and efficacy of ambrisentan in patients with PoPH in four German university hospitals. RESULTS: 14 patients with moderate to severe PoPH were included. The median follow-up was 16 months (IQR, 12 - 21). 6 minute walk tests after 6 and 12 months improved from 376 meters (IQR, 207 - 440) at baseline to 415 meters (IQR, 393 - 475; p = 0.011) and 413 meters (IQR, 362 - 473, p = 0.005), respectively. WHO- functional class after 1 year of therapy with ambrisentan also improved significantly (p = 0.014). No significant changes in blood gas analysis and liver function tests (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and international normalized ratio) during therapy with ambrisentan were detectable. CONCLUSIONS: The present study demonstrates significant improvement of exercise capacity and clinical symptoms without relevant safety concerns during ambrisentan treatment in patients with PoPH.

[Hemoptysis because of pulmonary vein stenosis and occlusion after pulmonary vein isolation for atrial fibrillation]. / Hämoptysen infolge Pulmonalvenenstenose und -verschluss nach Pulmonalvenen-Isolation bei Vorhofflimmern.

HISTORY AND ADMISSION FINDINGS: A 49-year-old woman was admitted because of hemoptysis for four months. Several bronchoscopies and thoracic computed tomographies at other hospitals had not revealed the cause of the sustained hemoptysis. Eight months before admission she had undergone pulmonary vein ablation (PVA) for paroxysmal atrial fibrillation. After the PVA she had initially received oral anticoagulation, but this had been stopped because of the hemoptysis. Physical examination at admission to our hospital was unremarkable except for moderate obesity and arterial hypertension INVESTIGATIONS: Ventilation/perfusion scintigraphy demonstrated combined ventilation and perfusion deficits in the left lower lobe. Transesophageal echocardiography strongly suggested stenoses of the left pulmonary veins. 3-D reconstruction of previously recorded computed tomographic images showed absence of the left inferior pulmonary vein (LIPV) and marked stenosis of the left superior pulmonary vein (LSPV). DIAGNOSIS: It was confirmed that the hemoptysis was caused by stenosis of the left pulmonary veins, resulting from the previous PVA. TREATMENT AND COURSE: Percutaneous transseptal balloon dilatation of the upper and lower pulmonary veins was successfully performed. The patient was put on oral anticoagulation and discharged home free of symptoms. CONCLUSION: Pulmonary vein stenosis must be considered as the most likely cause of hemoptysis and respiratory symptoms after pulmonary vein ablation for atrial fibrillation. Because of ever more frequent interventions to treat atrial fibrillation and other atrial arrhythmias, great clinical vigilance and an interdisciplinary approach is mandatory to assure optimal assessment of patients with acquired pulmonary vein stenosis.

[Acute pulmonary embolism]. / Die akute Lungenembolie.

Acute pulmonary embolism (APE) presents with a broad clinical spectrum ranging from an even asymptomatic course to sudden cardiac death. Because APE is potentially life-threatening every suspicion of APE has to be clarified promptly by validated diagnostic algorithms. On the basis of the patients haemodynamic instability high-risk APE and non-high-risk APE is differentiated. Based on the presence of shock or hypotension every patient with suspicion of APE should promptly be stratified as high-risk APE or non-high-risk APE. There is a considerable difference in the diagnostic and therapeutic algorithms between high-risk and non-high-risk APE. In suspicion of high-risk APE the patients require immediate diagnosis by multidetector CT or echocardiography and immediate recanalization of the occluded pulmonary arteries by thrombolysis or embolectomy. In haemodynamically stable patients sequential diagnostic workup and prompt therapeutic anticoagulation is recommended.