Sandra Riedel

A novel immune biomarker IFI27 discriminates between influenza and bacteria in patients with suspected respiratory infection

Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers. In this study, we combined an integrated genomic analysis of 1071 individuals with in vitro experiments using well-established infection models. We identified a single-gene biomarker, IFI27, which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers. In vitro studies showed that IFI27 was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria. In vivo studies confirmed that IFI27 was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions), IFI27 displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections. IFI27 represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting; its implementation may improve the diagnosis and management of respiratory infection. IFI27 could discriminate between influenza and bacterial infection in suspected respiratory tract infection cases http://ow.ly/VEaY30bmlS3

Pulmonales kapilläres Blutvolumen und Membrankomponente der pulmonalen Diffusionskapazität bei Patienten mit chronisch obstruktiver Bronchitis (COPD)

Reduced pulmonary diffusion capacity is a hallmark of COPD, although the relative contribution of the subcomponents of pulmonary diffusion--membranous component (Dm) and capillary volume (Vc)--is unknown. These components can be measured with the method of NO single-breath diffusion (DLNO). In a prospective study, pulmonary function tests including spirometry, body plethysmography and single-breath measurements of diffusion capacity with CO and NO were performed in 183 patients with COPD of varying severity. There was a severity-dependent decrease in DLCO. Furthermore, Dm as well as Vc was positively correlated with the severity of COPD measured by FEV1. In all stages of COPD, reduction of Vc was more pronounced than constriction of Dm. In patients with most severe COPD, the preponderance of the reduction of Vc was significantly more marked than in milder stages.We conclude that Dm as well as Vc contributes to the reduction of DLCO in COPD, with a predominance of Vc at all stages of COPD. This confirms the idea that the loss of pulmonary capillaries in COPD is functionally relevant.

Dual time point imaging for F18-FDG-PET/CT does not improve the accuracy of nodal staging in non-small cell lung cancer patients

ObjectivesTo analyze the diagnostic performance of dual time point imaging (DTPI) for pre-therapeutic lymph node (LN) staging in non-small cell lung cancer (NSCLC).MethodsThis was a retrospective analysis of 47 patients with NSCLC who had undergone DTPI by PET (early + delayed) using F18-fluorodeoxyglucose (FDG). PET raw data were reconstructed iteratively (point spread function + time-of-flight). LN uptake in PET was assessed visually (four-step score) and semi-quantitatively (SUVmax, SUVmean, ratios LN/primary, LN/liver, and LN/mediastinal blood pool). DTPI analyses included retention indices (RIs), Δ-ratios and changes in visual score. Histology or cytology served as standards of reference. Accuracy was determined based on ROC analyses.ResultsThirty-six of 155 LNs were malignant. DTPI accuracy was low for all measures (visual assessment, 24.5%; RI SUVmax, 68.4%; RI SUVmean, 65.8%; Δ-ratios, 63.9-76.1%) and significantly inferior to early PET. Accuracies of early (range, 86.5–92.9%) and delayed PET (range, 85.2–92.9%) were comparable. At early PET, accuracy of the visual score (92.9%) was similar or superior to semi-quantitative analyses (range, 86.5–92.3%).ConclusionsUsing a modern PET/CT device and novel image reconstruction, neither additional delayed PET nor DTPI analyses improved the accuracy of PET-based LN staging. Dedicated visual assessment criteria performed very well.Key Points• DTPI did not improve accuracy of PET-based LN staging in NSCLC.• Analyzed SUV ratios were not superior to LN SUVmax or SUVmean.• A four-step visual score may allow highly accurate, standardized LN assessment.

Impact of thoracic surgery on esophageal motor function—Evaluation by high resolution manometry

BACKGROUND Alteration of esophageal function is a potential risk factor for postoperative complications in thoracic surgery. This prospective study investigates esophageal motility and function during and after thoracic procedures via high resolution manometry (HRM) and impedance technology with spatiotemporal representation of pressure data. METHODS Twelve consecutive patients eligible for elective thoracic surgery underwent preoperative and postoperative (48 hours and 7 days) esophageal HRM. Swallowing acts were carried out with 5 mL of water, 10 mL of water and 1 cm3 bread in physiological posture to evaluate distal contraction integral (DCI). Length and location of contractile integrity breaks were measured by investigators blinded to the form of surgical intervention. The impact of surgical procedures on esophageal motility was quantified according to current Chicago Classification (CC) criteria. Pre-, intra- and postoperative 24-hour multi-channel impedance pH-metry (MII-pH) was performed to further analyze gastroesophageal reflux patterns. RESULTS All patients were investigated 48 hours prior to and 7 days after thoracic procedures, with a total of n=675 swallowing acts being included in our study. Increased motility patterns of the tubular esophagus occurred temporally 48 hours postoperatively. DCI 48 hours after surgery increased significantly (5 mL, P=0.049; solid, P=0.014) and returned to baseline values after seven days (5 mL, P=0.039; solid, P=0.039). Break length was significantly reduced 48 hours postoperatively, especially in the proximal esophageal segment (transition zone). Follow-up measurements after another week were comparable to preoperative baseline findings. The perioperative MII-pH measurement showed numerous artifacts caused by intubation and ventilation during surgery also with increasing short and frequent acidic reflux episodes. CONCLUSIONS Thoracic procedures cause a transient modulation of esophageal peristalsis with postoperative increased contractility of the tubular esophagus, presumably without affecting intraesophageal reflex arcs. Although limited by the number of patients, we can conclude on our data that postoperative esophageal hypomotility is unlikely to promote secondary pulmonary complications.

Behandlung von Dyspnoe und Husten am Lebensende

ZusammenfassungHusten und Luftnot gehören zu den häufigsten Symptomen bei Patienten mit fortgeschrittenen malignen und nicht malignen Erkrankungen unter Beteiligung des respiratorischen Systems in der terminalen Lebensphase. Die sogenannte refraktäre Dyspnoe kann mithilfe eines multimodalen Therapiekonzeptes bestehend aus Allgemeinmaßnahmen, nicht pharmakologischer und medikamentöser Therapie meist gut gelindert werden. Bei quälendem chronischem Husten stehen leider deutlich weniger Behandlungsoptionen zur Verfügung. Hier werden hauptsächlich pharmakologische Therapieansätze verfolgt.

Occult interferon α-induced pulmonary granulomatosis despite continuation of treatment.

Interferon alpha (IFN α)-based treatment of chronic hepatitis C viral (HCV) infection may induce pulmonary and extrapulmonary sarcoidosis. We report a case of a 50-year-old male patient who suffered from hepatitis C-induced liver cirrhosis with respiratory insufficiency due to severe hepatopulmonary syndrome. After 9 months of treatment with IFNα and ribavirin, he developed an asymptomatic, clinically occult pulmonary granulomatosis, which was not detectable in CT. The diagnosis was made by bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsy. The condition did not progress to clinically apparent disease despite continuation of IFN alpha treatment.