Frederike Reischies

Diagnostic accuracy of the Aspergillus-specific bronchoalveolar lavage lateral-flow assay in haematological malignancy patients.

We evaluated the performance of the Aspergillus‐specific lateral‐flow device (LFD) test for diagnosing invasive pulmonary aspergillosis (IPA) in patients with underlying haematological malignancies. Participating centres were the two Austrian University Hospitals of Graz and Innsbruck. LFD performance was evaluated with 95 bronchoalveolar lavage fluid (BALF) samples from 72 patients collected prospectively in Graz, and with 24 BALF bio bank samples from 23 patients (21 samples with probable IPA) in Innsbruck. Invasive fungal infections were classified according to the revised European Organization of Research and Treatment of Cancer/Mycoses Study Group criteria. Overall, 27 patients (30 samples) had probable IPA, 32 (43 samples) possible and 36 (46 samples) did not fulfil IPA criteria. The vast majority of patients – in particular those with probable IPA – received mould‐active treatment before bronchoscopy. Sensitivity, specificity, positive predictive value and negative‐predictive‐value for probable IPA diagnosis using the BALF‐LFD test were 71%, 76%, 35% and 94% for the Graz cohort. Sensitivity of the BALF‐LFD test for probable IPA was 57% in Innsbruck bio bank samples. Our results indicate that the BALF‐LFD‐test provides fast results with moderate sensitivities in patients with underlying haematological malignancies. Similar to other diagnostic tests and biomarkers sensitivity of the test may be influenced by ongoing systemic mould‐active treatment.

Influence of mould-active antifungal treatment on the performance of the Aspergillus-specific bronchoalveolar lavage fluid lateral-flow device test

The effect of mould-active antifungal (AF) therapy/prophylaxis on the performance of the Aspergillus-specific lateral-flow device (LFD) test for diagnosing invasive pulmonary aspergillosis (IPA) was evaluated. This was a retrospective analysis of patients diagnosed with probable or proven IPA (according to revised EORTC/MSG criteria) at the Medical University of Graz (Austria) and the University Hospital of Mannheim (Germany) between February 2011 and December 2014. In total, 60 patients with 63 bronchoalveolar lavage fluid (BALF) samples were included in the analysis. Patient charts were reviewed regarding AF treatment at the time of bronchoscopy, and the influence of AFs on the performance of the LFD and BALF galactomannan (GM) ELISA results was calculated. Overall, 54 patients (57 BALF samples) had probable IPA and 6 patients (6 samples) had proven IPA. In 21/63 samples (33%) (from 19 patients), systemic mould-active AFs had been initiated before bronchoscopy. Of 63 BALF samples, 16 (25%) yielded a false-negative LFD result. The sensitivity of the LFD for probable/proven IPA was significantly lower in those receiving mould-active AFs compared with those without (52% vs. 86%; P=0.006). Similar results were found for BALF GM, with sensitivities decreasing under systemic AFs (71% vs. 95%, P=0.013 with the 0.5 ODI cut-off; 52% vs. 81%, P=0.036 with the 1.0 cut-off). These results suggest that the sensitivity of the BALF LFD and BALF GM assays may be reduced in the presence of mould-active AF treatment. Negative results in patients on AFs should therefore be interpreted with caution.

Multicenter evaluation of a lateral-flow device test for diagnosing invasive pulmonary aspergillosis in ICU patients

IntroductionThe incidence of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is increasing, and early diagnosis of the disease and treatment with antifungal drugs is critical for patient survival. Serum biomarker tests for IPA typically give false-negative results in non-neutropenic patients, and galactomannan (GM) detection, the preferred diagnostic test for IPA using bronchoalveolar lavage (BAL), is often not readily available. Novel approaches to IPA detection in ICU patients are needed. In this multicenter study, we evaluated the performance of an Aspergillus lateral-flow device (LFD) test for BAL IPA detection in critically ill patients.MethodsA total of 149 BAL samples from 133 ICU patients were included in this semiprospective study. Participating centers were the medical university hospitals of Graz, Vienna and Innsbruck in Austria and the University Hospital of Mannheim, Germany. Fungal infections were classified according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria.ResultsTwo patients (four BALs) had proven IPA, fourteen patients (sixteen BALs) had probable IPA, twenty patients (twenty-one BALs) had possible IPA and ninety-seven patients (one hundred eight BALs) did not fulfill IPA criteria. Sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratios for diagnosing proven and probable IPA using LFD tests of BAL were 80%, 81%, 96%, 44% and 17.6, respectively. Fungal BAL culture exhibited a sensitivity of 50% and a specificity of 85%.ConclusionLFD tests of BAL showed promising results for IPA diagnosis in ICU patients. Furthermore, the LFD test can be performed easily and provides rapid results. Therefore, it may be a reliable alternative for IPA diagnosis in ICU patients if GM results are not rapidly available.Trial registrationClinicalTrials.gov NCT02058316. Registered 20 January 2014.

Diagnostic performance of 1,3-beta-D-glucan serum screening in patients receiving hematopoietic stem cell transplantation.

The polysaccharide cell wall component, 1,3‐beta‐D‐glucan (BDG), is used as a serum biomarker for invasive fungal infection (IFI). Patients receiving hematopoietic stem cell transplantation (HSCT) are considered a highly vulnerable group for IFI development. We evaluated the diagnostic performance of serum BDG screening in HSCT recipients.

Detection of (1→3)‐β‐D‐glucan in same‐day urine and serum samples obtained from patients with haematological malignancies

Serum 1,3‐beta‐d‐glucan (BDG) testing is an established diagnostic marker for invasive fungal infections (IFI) among patients with haematological malignancies. In contrast limited data exist regarding the application of urine BDG testing. Same‐day midstream urine and serum screening samples were collected in adult patients with underlying haematological malignancies. A total of 80 urine samples from 46 patients were investigated: Twenty‐six had positive corresponding serum BDG >120 pg ml−1, 27 intermediate (60–80 pg ml−1), and 27 negative serum BDG (<25 pg ml−1). A significant positive correlation between BDG in serum and urine samples was observed (P = 0.025; r = 0.252). Sensitivity, specificity, positive predictive value and negative predictive value (compared with same‐day serum results) were: 42%, 76%, 46%, 73% when using an 80 pg ml−1 urine cut‐off, and 35%, 96%, 82%, 75% for a 250 pg ml−1 cut‐off. Urine BDG seemed to be higher in samples obtained from patients with probable IFI (n = 13, median 145, IQR 22–253) compared to those from patients without IFI (n = 56, median 24, IQR 15–88) but the difference was not significant (P = 0.069). Overall correlation of same‐day urine BDG and serum BDG was moderate. However, urine BDG testing may warrant further investigation in larger studies, as high‐positive urine results correlated with high‐positive corresponding serum levels and clinical performance was comparable to serum BDG.

The role of surgical debridement in different clinical manifestations of invasive aspergillosis

Invasive aspergillosis (IA) has a wide spectrum of clinical presentations and is associated with high mortality rates. Early initiation of systemic antimould therapy remains the most important measure to reduce mortality. Surgical debridement is an important additional therapeutic option mainly in cases of extrapulmonary IA. The main intention for surgical intervention in IA is to obtain material for diagnosis and antifungal susceptibility testing. There are, however, also therapeutic implications for surgical interventions in rare manifestation of IA such as endocarditis or mycotic aneurysm. Here, we will review the role of surgical interventions in the treatment of different clinical manifestations of IA.

Urine Galactomannan-to-Creatinine Ratio for Detection of Invasive Aspergillosis in Patients with Hematological Malignancies

ABSTRACT Galactomannan (GM) testing of urine specimens may provide important advantages, compared to serum testing, such as easy noninvasive sample collection. We evaluated a total of 632 serial urine samples from 71 patients with underlying hematological malignancies and found that the urine GM/creatinine ratio, i.e., (urine GM level × 100)/urine creatinine level, which takes urine dilution into account, reliably detected invasive aspergillosis and may be a promising diagnostic tool for patients with hematological malignancies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01576653.)

Invasive aspergillosis in patients with underlying liver cirrhosis: a prospective cohort study

The aim of this study was to determine the prevalence of invasive aspergillosis (IA) in patients with liver cirrhosis and the performance of serum galactomannan (GM) screening. Patients with decompensated liver cirrhosis and patients with compensated liver cirrhosis presenting with fever and/or respiratory symptoms were prospectively enrolled. All patients were screened by serum GM twice weekly irrespective of clinical signs and symptoms. Positive serum GM triggered work-up consisting of chest computed tomography and in case of pathological findings bronchoscopy. 150 patients were included in the study. Two (1.3%) had probable, one (0.7%) had possible, and 147 (98%) had no evidence of IA. Both patients with probable IA had compensated liver cirrhosis. Sensitivity for serum GM screening for probable versus no IA was 0.5 (95% CI, 0.09-0.91), specificity 0.97 (95% CI: 0.92-0.99), negative predictive value 0.99 (95% CI, 0.96-0.99) and positive predictive value (PPV) 0.17 (95% CI, 0.01-0.64). PPV was 0.5 (95% CI, 0.03-0.98) in patients with clinical suspicion of IA. In conclusion, prevalence of IA in patients with liver cirrhosis seems to be low. Targeted GM testing in case of clinical suspicion of IA may be associated with markedly higher PPVs when compared to universal GM screening in patients with liver cirrhosis.

Standardizing the complication rate after breast reduction using the Clavien-Dindo classification

Background. Published complication rates for breast reduction surgery, also known as reduction mammaplasty, vary between 4% and 54%. This wide range of complication rates could be attributable to the lack of a standardized classification of complications in plastic surgery. The aim of this study was to analyze our single‐center complication rates after reduction mammaplasty using the Clavien‐Dindo classification. Methods. We performed a retrospective chart review studying 804 patients between the ages of 18 and 81 years old who underwent breast reduction between 2005 and 2015 at our institution. Patients with a history of breast cancer, a previous breast operation, who did not undergo bilateral reduction mammaplasty, or who required systemic immunodeficiency/immunosuppressive drugs were excluded from our analysis. Complications were classified according to the Clavien‐Dindo classification from Grades I to V. Results. A total of 486 patients met the inclusion criteria for the analysis. Patients had an age (mean ± standard deviation) of 39 ± 13 years and a body mass index of 26 ± 4 kg/m2. Median follow‐up was 274 days (interquartile range: 90.5–378). The overall rate of complications of reduction mammaplasty was 63%, with the majority of those being Grades I (48%) and II (9%), comprising 92% of all the complications. Operative revisions were required in 6% (1% Grade IIIA and 5% Grade IIIB). There were no complications graded in categories IV and V. Conclusion. Although complications occurred in more than half of the cases, the majority did not require operative reintervention. The Clavien‐Dindo classification can classify the severity of complications and serve as a benchmark to compare complication rates between different practices. We believe that grading of complications should distinguish between those that do and do not require operative reinterventions.

1462Bronchoalveolar Lavage Lateral-Flow Device Test for Diagnosing Invasive Pulmonary Aspergillosis in ICU patients: a multicenter study

Invasive Pulmonary Aspergillosis in ICU patients: a multicenter study Martin Hoenigl, MD; Jürgen Prattes, MD; Susanne Eigl, MD; Cornelia Lass-Flörl, MD; Birgit Willinger, MD; Frederike Reischies; Verena Posch; Michaela Lackner PHD; Holger Flick, MD; Katharina Hönigl; Christoph Koidl; Christopher Thornton PHD; Robert Krause, MD; Section of Infectious Diseases, Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Medical University of Graz, Graz, Austria; Section of Infectious Diseases and Tropical Medicine, Medical University of Graz, Graz, Austria; Institute of Hygiene and Social Medicine, Innsbruck, Austria; Medical University of Vienna, Vienna, Austria; Innsbruck Medical University, Innsbruck, Austria; Divison of Pulmonology, Medical University of Graz, Graz, Austria; Institute of Hygiene, Medical University of Graz, Graz, Austria; Biosciences, University of Exeter, Exeter, United Kingdom