Association between Parenchymal B-Cell Follicles and CT-Proven Enlarged Mediastinal Lymph Nodes in Patients with Pulmonary Fibrosis.

BACKGROUND: Mediastinal lymph node enlargement (MLNE) is a finding described in a subset of patients with idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs) and is associated with accelerated disease progression and increased mortality. The cause of MLNE is still not known. Our hypothesis is that there is an association between MLNE and B-cell follicles in lung tissue, another aspect detectable in the lung tissue of patients with IPF and other ILDs. OBJECTIVES: The aim of this study was to assess if there is an association between MLNE and B-cell follicles in lung tissue in patients with IPF and other ILDs. METHOD: Patients having transbronchial cryobiopsies performed as part of an investigation for ILD were included in this prospective observational study. MLNE (smallest diameter ≥10 mm) were assessed in station 7, 4R, and 4L on high-resolution computed tomography scans. B-cell follicles were assessed on haematoxylin-eosin-stained specimens. Lung function, 6-minute walk test, acute exacerbation, and mortality were registered after 2 years. In addition, we investigated if the finding of B-cell follicles was consistent in patients who underwent both surgical lung biopsies (SLBs) and cryobiopsies. RESULTS: In total, 93 patients were included for analysis (46% diagnosed with IPF, 54% diagnosed with other ILDs). MLNE was found in 26 (60%) of the IPF patients and in 23 (46%) of the non-IPF patients (p = 0.164). Diffusing capacity for carbon monoxide was significantly lower (p = 0.03) in patients with MLNE compared to patients without MLNE. B-cell follicles were found in 11 (26%) of the IPF patients and in 22 (44%) of the non-IPF patients (p = 0.064). Germinal centres were not seen in any of the patients. There was no association between MLNE and B-cell follicles (p = 0.057). No significant difference in change of pulmonary function test was seen at 2-year follow-up when comparing the patients with and without MLNE or B-cell follicles. In 13 patients, both SLBs and cryobiopsies were performed. The presence of B-cell follicles was not consistent when comparing the two different methods. CONCLUSION: MLNE is evident in a substantial part of patients with ILD and is associated with lower DLCO at inclusion. We could not demonstrate an association between histological B-cell follicles in biopsies and MLNE. A possible explanation for this is that the cryobiopsies might not have captured the changes we sought.

Programmed death-ligand 1 expression influenced by tissue sample size. Scoring based on tissue microarrays' and cross-validation with resections, in patients with, stage I-III, non-small cell lung carcinoma of the European Thoracic Oncology Platform Lungscape cohort.

PD-L1, as assessed by immunohistochemistry, is a predictive biomarker for immuno-oncology treatment in lung cancer. Different scoring methods have been used to assess its status, resulting in a wide range of positivity rates. We use the European Thoracic Oncology Platform Lungscape non-small cell lung carcinoma cohort to explore this issue. PD-L1 expression was assessed via immunohistochemistry on tissue microarrays (up to four cores per case), using the DAKO 28-8 immunohistochemistry assay, following a two-round external quality assessment procedure. All samples were analyzed under the same protocol. Cross-validation of scoring between tissue microarray and whole sections was performed in 10% randomly selected samples. Cutoff points considered: ≥1, 50 (primarily), and 25%. At the two external quality assessment rounds, tissue microarray scoring agreement rates between pathologists were: 73% and 81%. There were 2008 cases with valid immunohistochemistry tissue microarray results (50% all cores evaluable). Concordant cases at 1, 25, and 50% were: 85, 91, and 93%. Tissue microarray core results were identical for 70% of cases. Sensitivity of the tissue microarray method for 1, 25, and 50% was: 80, 78, and 79% (specificity: 90, 95, 98%). Complete agreement between tissue microarrays and whole sections was achieved for 60% of the cases. Highest sensitivity rates for 1% and 50% cutoffs were detected for higher number of cores. Underestimation of PD-L1 expression on small samples is more common than overestimation. We demonstrated that classification of PD-L1 on small biopsy samples does not represent the overall expression of PD-L1 in all non-small cell cancer carcinoma cases, although the majority of cases are 'correctly' classified. In future studies, sampling more and larger biopsies, recording the biopsy size and tumor load may permit further refinement, increasing predictive accuracy.

Cholinergic PET imaging in infections and inflammation using 11C-donepezil and 18F-FEOBV.

INTRODUCTION: Immune cells utilize acetylcholine as a paracrine-signaling molecule. Many white blood cells express components of the cholinergic signaling pathway, and these are up-regulated when immune cells are activated. However, in vivo molecular imaging of cholinergic signaling in the context of inflammation has not previously been investigated. METHODS: We performed positron emission tomography (PET) using the glucose analogue 18F-FDG, and 11C-donepezil and 18F-FEOBV, markers of acetylcholinesterase and the vesicular acetylcholine transporter, respectively. Mice were inoculated subcutaneously with Staphylococcus aureus, and PET scanned at 24, 72, 120, and 144 h post-inoculation. Four pigs with post-operative abscesses were also imaged. Finally, we present initial data from human patients with infections, inflammation, and renal and lung cancer. RESULTS: In mice, the FDG uptake in abscesses peaked at 24 h and remained stable. The 11C-donepezil and 18F-FEOBV uptake displayed progressive increase, and at 120-144 h was nearly at the FDG level. Moderate 11C-donepezil and slightly lower 18F-FEOBV uptake were seen in pig abscesses. PCR analyses suggested that the 11C-donepezil signal in inflammatory cells is derived from both acetylcholinesterase and sigma-1 receptors. In humans, very high 11C-donepezil uptake was seen in a lobar pneumonia and in peri-tumoral inflammation surrounding a non-small cell lung carcinoma, markedly superseding the 18F-FDG uptake in the inflammation. In a renal clear cell carcinoma no 11C-donepezil uptake was seen. DISCUSSION: The time course of cholinergic tracer accumulation in murine abscesses was considerably different from 18F-FDG, demonstrating in the 11C-donepezil and 18F-FEOBV image distinct aspects of immune modulation. Preliminary data in humans strongly suggest that 11C-donepezil can exhibit more intense accumulation than 18F-FDG at sites of chronic inflammation. Cholinergic PET imaging may therefore have potential applications for basic research into cholinergic mechanisms of immune modulation, but also clinical applications for diagnosing infections, inflammatory disorders, and cancer inflammation.

Interstitial lung disease was suspected, but biopsy revealed pulmonary lymphangitis carcinomatosa.

Introduction: Pulmonary lymphangitis carcinomatosa is a rare and severe manifestation of metastatic disease that causes pulmonary symptoms and radiologic patterns similar to interstitial lung diseases. Case presentation: We report a case of a 78-year-old woman who presented to our department with insidiously developed symptoms of fatigue, dry cough, and severe dyspnea for 3 months. Chest radiography showed bilateral interstitial changes. On suspicion of interstitial lung disease, bronchoscopy and transbronchial cryobiopsy were carried out. Surprisingly, histopathological investigation revealed pulmonary lymphangitis carcinomatosa originating from primary breast adenocarcinoma. Conclusion: To achieve an accurate diagnosis and prevent delay of initiation of proper treatment a thorough diagnostic approach is necessary. In case of doubt, biopsy should be performed to secure clarification. In this case report we discuss the diagnostic value of transbroncial cryobiopsy for this purpose.

Exogenous lipoid pneumonia due to silent aspiration following surgery and radiotherapy for cancer of the tongue.

A man with a history of cancer of the base of the tongue presenting with hemoptysis, recurrent pneumonia and crazy-paving patterns on CT was ultimately diagnosed with lipoid pneumonia, subsequently found to be associated with use of fish oil capsules and possible Parkinson's disease. Pulmonary alveolar proteinosis and invasive mucinous adenocarcinoma as differential diagnoses were considered and dismissed. Risk of aspiration and lipoid pneumonia should be considered in patients with similar radiological findings and history.

TDP1 and TOP1 as targets in anticancer treatment of NSCLC: Activity and protein level in normal and tumor tissue from 150 NSCLC patients correlated to clinical data.

OBJECTIVES: Topoisomerase 1 (TOP1) is a drug target used in anticancer treatment of various cancer types. The effect of the TOP1 drugs can be counteracted by the enzymatic activity of tyrosyl-DNA phosphodiesterase 1 (TDP1). Thus, to elucidate the relevance of combining TDP1 and TOP1 as drug targets for anticancer treatment in NSCLC, TDP1 and TOP1 was for the first time quantified in a large cohort of paired normal and tumor tissue from NSCLC patients, and data were correlated between the two enzymes and to clinical data. MATERIALS AND METHODS: TDP1 and TOP1 activity and protein concentration were measured in paired normal and tumor tissue from 150 NSCLC patients using TDP1 and TOP1 specific biosensors and ELISA. TDP1 and TOP1 activity and protein concentration were correlated to clinical data. RESULTS: TDP1 and TOP1 activity and protein concentration were significantly upregulated from normal to tumor tissue for the individual patients, but did not correlate to any of the clinical data. TDP1 and TOP1 activity were upregulated in 89.3% and 82.7% of the patients, respectively, and correlated in both normal and tumor tissue. The same tendency was observed for protein concentration with an upregulation of TDP1 and TOP1 in 73.0% and 84.4% of the patients, respectively. The activity and protein concentration correlated in normal and tumor tissue for both TDP1 and TOP1. CONCLUSION: The upregulations of TDP1 and TOP1 from normal to tumor tissue combined with the observation that TDP1 and TOP1 did not correlate to any of the clinical data indicate that both proteins are important for development or maintenance of the tumor cells in NSCLC. Correlations between TDP1 and TOP1 indicate a biological dependency and potential co-regulation of the enzymes. These observations is encouraging in relation to using TOP1 and TDP1 as targets in anticancer treatment of NSCLC.

Economic evaluation of home blood pressure telemonitoring: a randomized controlled trial.

AIMS: The purpose of the present study was to compare the costs of home blood pressure (BP) telemonitoring (HBPM) with the costs of conventional office BP monitoring. In a randomized controlled trial, 105 hypertensive patients performed HBPM and 118 patients received usual care with conventional office BP monitoring during 6 months. Costs were quantified from the healthcare perspective. Non-parametric simulations were performed to quantify the uncertainty around the mean estimates and cost-effectiveness acceptability curves were made. MAJOR FINDINGS: Systolic and diastolic daytime and night-time ambulatory BP (ABP) were reduced in both groups. The uncertainty around the incremental cost effectiveness ratio point estimates was considerable for both systolic and diastolic ABP. For systolic ABP, the difference in cost effectiveness ratio between the two groups was 256 Danish kroner (DKK)/mmHg [95% uncertainty interval, UI -860 to 4544]. For diastolic ABP, the difference in cost effectiveness ratio between the two groups was 655 DKK/mmHg [95% UI -674 to 69315]. Medication and consultation costs were lowest in the intervention group, but were offset by the cost of the telemonitoring equipment. CONCLUSIONS: Cost-effectiveness analysis showed that telemonitoring of home BP was more costly compared with usual monitoring of office BP. The cost-effectiveness result is surrounded with considerable uncertainty.

PD-L1 Expression in Patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common and severe form within the group of idiopathic interstitial pneumonias. It is characterized by repetitive alveolar injury in genetically susceptible individuals and abnormal wound healing, leading to dysregulated bronchiolar proliferation and excessive deposition of extracellular matrix, causing complete architectural distortion and fibrosis. Epithelial-to-mesenchymal transition is considered an important pathogenic event, a phenomenon also observed in various malignant neoplasms, in which tumor cells express programmed death-ligand one (PD-L1). The aim of this study was to assess the presence of PD-L1 in patients with IPF and other interstitial lung diseases (ILDs). METHOD: Patients with a clinically and radiologically suspected idiopathic interstitial pneumonia or other ILDs undergoing transbronchial cryobiopsy to confirm the diagnosis at the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, were included in this prospective observational study. Cellular membrane PD-L1 expression in epithelial cells was determined using the DAKO PD-L1 IHC 22C3 PharmDx Kit. RESULTS: Membrane-bound PD-L1 (mPD-L1) was found in twelve (28%) of the forty-three patients with IPF and in five (9%) of the fifty-five patients with other ILDs (p = 0.015). When adjusting for age, gender and smoking status, the odds ratio of having IPF when expressing mPD-L1 in alveolar and/or bronchiolar epithelial cells was 4.3 (CI: 1.3-14.3). CONCLUSION: Expression of mPD-L1 in epithelial cells in the lung parenchymal zones was detected in a consistent subgroup of patients with IPF compared to other interstitial pneumonias. Larger studies are needed to explore the role of mPD-L1 in patients with IPF.

International multidisciplinary team discussions on the diagnosis of idiopathic non-specific interstitial pneumonia and the development of connective tissue disease.

BACKGROUND: Idiopathic Non-Specific Interstitial Pneumonia (iNSIP) is a rare interstitial lung disease, diagnosed, by definition, on the basis of a multidisciplinary team discussion (MDD). Association with an autoimmune background has been suggested in iNSIP. AIMS: To test the feasibility of conducting a multinational MDD to review the diagnosis in iNSIP cases and to estimate the emergence of connective tissue disease (CTD) during follow-up. METHODS: Investigators from three expert centers (Denmark, Estonia and Norway) met and discussed cases of biopsy-proven iNSIP at an international MDD. The cases were previously diagnosed at a national level between 2004 and 2014. Based on clinical, radiographic and pathological data, the diagnosis of iNSIP was re-evaluated and a consensus diagnosis was made. Cases incompatible with iNSIP were excluded. Relevant data were registered comprising any development of CTD. RESULTS: In total, 31 cases were discussed and 23 patients were included with a diagnosis of iNSIP. The mean follow-up time was 57 months. None of the patients developed CTD according to the rheumatologic criteria during the follow up period. Four patients (17.4%) met the criteria for interstitial pneumonia with autoimmune features. CONCLUSION: We found that an international MDD was a feasible and valuable tool in the retrospective diagnostic evaluation of iNSIP. Diagnosis was changed in a statistically significant number of patients by our international MDD team. None of the patients developed CTD during follow-up.

Integration of cryobiopsies for interstitial lung disease diagnosis is a valid and safe diagnostic strategy-experiences based on 250 biopsy procedures.

BACKGROUND: Transbronchial cryobiopsies has become increasingly used in the diagnostic workup in patients suspected of having interstitial lung disease. The procedure is associated with less complications, morbidity and mortality compared to surgical lung biopsies although with a diagnostic yield that is not as high, but close to that of surgical lung biopsies. The aim of the present study was to describe the complications and diagnostic yield and their prognostic factors. METHODS: All patients undergoing transbronchial cryobiopsies at the Department of Respiratory Diseases and Allergy, Aarhus University Hospital, were included in this prospective observational cohort study. RESULTS: A total of 250 patients were included [61% male, mean age 66 years (range, 22-81 years)]. Pneumothorax was detected in 70 (28%) of the patients, moderate hemorrhage in 53 (21%) and severe hemorrhage in 2 (1%) of the patients. Hemorrhage was associated with central biopsies, but not with anticoagulant therapy. None of the complications were related to lung function, exercise capacity, biopsy or probe size. Only one patient experienced an acute exacerbation. Three-month mortality was 0.4% (1 patient), caused by cancer and unrelated to the procedure. Cryobiopsies contributed to the final diagnosis in 72% of the patients and after multidisciplinary team discussion, a consensus diagnosis was obtained in 82% of the patients. The gender, the total sum of biopsy sizes, number of biopsies and presence of more than 50% alveolar tissue in biopsies increased the diagnostic yield. CONCLUSIONS: Our study confirms that using cryobiopsies in the diagnostic setup for interstitial lung diseases is safe with a limited risk of acute exacerbations and mortality. Cryobiopsies contribute to the diagnosis in the majority of patients.

Prognostic Impact of KRAS G12C Mutation in Patients With NSCLC: Results From the European Thoracic Oncology Platform Lungscape Project.

INTRODUCTION: KRAS mutations, the most frequent gain-of-function alterations in NSCLC, are currently emerging as potential predictive therapeutic targets. The role of KRAS-G12C (Kr_G12C) is of special interest after the recent discovery and preclinical analyses of two different Kr_G12C covalent inhibitors (AMG-510, MRTX849). METHODS: KRAS mutations were evaluated in formalin-fixed, paraffin-embedded tissue sections by a microfluidic-based multiplex polymerase chain reaction platform as a component of the previously published European Thoracic Oncology Platform Lungscape 003 Multiplex Mutation study, of clinically annotated, resected, stage I to III NSCLC. In this study, -Kr_G12C mutation prevalence and its association with clinicopathologic characteristics, molecular profiles, and postoperative patient outcome (overall survival, relapse-free survival, time-to-relapse) were explored. RESULTS: KRAS gene was tested in 2055 Lungscape cases (adenocarcinomas: 1014 [49%]) with I or II or III stage respective distribution of 53% or 24% or 22% and median follow-up of 57 months. KRAS mutation prevalence in the adenocarcinoma cohort was 38.0% (95% confidence interval (CI): 35.0% to 41.0%), with Kr_G12C mutation representing 17.0% (95% CI: 14.7% to 19.4%). In the "histologic-subtype" cohort, Kr_G12C prevalence was 10.5% (95% CI: 9.2% to 11.9%). When adjusting for clinicopathologic characteristics, a significant negative prognostic effect of Kr_G12C presence versus other KRAS mutations or nonexistence of KRAS mutation was identified in the adenocarcinoma cohort alone and in the "histologic-subtype" cohort. For overall survival in adenocarcinomas, hazard ratio (HR)G12C versus other KRAS is equal to 1.39 (95% CI: 1.03 to 1.89, p = 0.031) and HRG12C versus no KRAS is equal to 1.32 (95% CI: 1.03 to 1.69, p = 0.028) (both also significant in the "histologic-subtype" cohort). For time-to-relapse, HRG12C versus other KRAS is equal to 1.41 (95% CI: 1.03 to 1.92, p = 0.030). In addition, among all patients, for relapse-free survival, HRG12C versus no KRAS is equal to 1.27 (95% CI: 1.04 to 1.54, p = 0.017). CONCLUSIONS: In this large, clinically annotated stage I to III NSCLC cohort, the specific Kr_G12C mutation is significantly associated with poorer prognosis (adjusting for clinicopathologic characteristics) among adenocarcinomas and in unselected NSCLCs.

Fatal pulmonary fibrosis: a post-COVID-19 autopsy case.

There is growing evidence of histopathological changes in autopsied individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, data on histopathological changes in autopsied patients with eradicated COVID-19 are limited. We performed an autopsy on a Caucasian female in her 80s, who died due to severe, bilateral pulmonary fibrosis after eliminated SARS-CoV-2 infection. In addition, CT scans from 2 months before infection and from 6 days prior to death were compared. Comparison of the CT scans showed bilateral development of widespread fibrosis in previously healthy lungs. Microscopic examination showed different areas with acute and organising diffuse alveolar damage and fibrosis with honeycomb-like remodelling and bronchial metaplasia. We here report a unique autopsy case with development of widespread pulmonary fibrosis in a woman in her 80s with previous COVID-19 and no history of pulmonary illnesses.

A retrospective cohort study of PD-L1 prevalence, molecular associations and clinical outcomes in patients with NSCLC: Results from the European Thoracic Oncology Platform (ETOP) Lungscape Project.

INTRODUCTION: The PD-L1 biomarker is an important factor in selecting patients with non-small cell lung cancer for immunotherapy. While several reports suggest that PD-L1 positivity is linked to a poor prognosis, others suggest that PD-L1 positive status portends a good prognosis. METHODS: PD-L1 positivity prevalence, assessed via immunohistochemistry (IHC) on tissue microarrays (TMAs), and its association with clinicopathological characteristics, molecular profiles and patient outcome- Relapse-free Survival (RFS), Time-to-Relapse (TTR) and Overall Survival (OS)- is explored in the ETOP Lungscape cohort of stage I-III non-small cell lung cancer (NSCLC). Tumors are considered positive if they have ≥1/5/25/50% neoplastic cell membrane staining. RESULTS: PD-L1 expression was assessed in 2182 NSCLC cases (2008 evaluable, median follow-up 4.8 years, 54.6% still alive), from 15 ETOP centers. Adenocarcinomas represent 50.9% of the cohort (squamous cell: 42.4%). Former smokers are 53.7% (current: 31.6%, never: 10.5%). PD-L1 positivity prevalence is present in more than one third of the Lungscape cohort (1%/5% cut-offs). It doesn't differ between adenocarcinomas and squamous cell histologies, but is more frequently detected in higher stages, never smokers, larger tumors (1/5/25% cut-offs). With ≥1% cut-off it is significantly associated with IHC MET overexpression, expression of PTEN, EGFR and KRAS mutation (only for adenocarcinoma). Results for 5%, 25% and 50% cut-offs were similar, with MET being significantly associated with PD-L1 positivity both for AC (p < 0.001, 5%/25%/50% cut-offs) and SCC (p < 0.001, 5% & 50% cut-offs and p = 0.0017 for 25%). When adjusting for clinicopathological characteristics, a significant prognostic effect was identified in adenocarcinomas (adjusted p-values: 0.024/0.064/0.063 for RFS/TTR/OS 1% cut-off, analogous for 5%/25%, but not for 50%). Similar results obtained for the model including all histologies, but no effect was found for the squamous cell carcinomas. CONCLUSION: PD-L1 positivity, when adjusted for clinicopathological characteristics, is associated with a better prognosis for non-metastatic adenocarcinoma patients.

Familial idiopathic pulmonary fibrosis in a young female.

Idiopathic pulmonary fibrosis is a chronic interstitial lung disease of unknown cause. In the past years there have been observations of clustering of pulmonary fibrosis in families, indicating the disease can be inherited. The most commonly identified mutations are mutations involving proteins from the telomerase complex and the surfactant system, where the mutations from the surfactant protein system are less identified. We report a rare care of familial IPF in a young female at the age of 34 years, in whom genetic testing shows two different heterozygous variants for the surfactant protein system as a probable cause of her interstitial lung disease.

[Neurogenic autonomic dysfunction in primary amyliodosis].

Neurogenic autonomic dysfunction (NAD) and polyneuropathy occur in common conditions like diabetes and alcoholism. However, it can also be seen in rare diseases like in this case report of amyloid light-chain amyloidosis: primary amyloidosis. A 56-year-old man presented with polyneuropathy, a sympathetic dysfunction causing orthostatic intolerance, syncope, parasympathetic dysfunction and involvement of the enteric nervous system. The report illustrates, that routine screening can be insufficient in diagnosing amyloidosis. NAD and polyneuropathy without clear aetiology may require a multidisciplinary elucidation of more rare diseases.

Computer-Based Intensity Measurement Assists Pathologists in Scoring Phosphatase and Tensin Homolog Immunohistochemistry - Clinical Associations in NSCLC Patients of the European Thoracic Oncology Platform Lungscape Cohort.

INTRODUCTION: Phosphatase and tensin homolog (PTEN) loss is frequently observed in NSCLC and associated with both phosphoinositide 3-kinase activation and tumoral immunosuppression. PTEN immunohistochemistry is a valuable readout, but lacks standardized staining protocol and cutoff value. METHODS: After an external quality assessment using SP218, 138G6 and 6H2.1 anti-PTEN antibodies, scored on webbook and tissue microarray, the European Thoracic Oncology Platform cohort samples (n = 2245 NSCLC patients, 8980 tissue microarray cores) were stained with SP218. All cores were H-scored by pathologists and by computerized pixel-based intensity measurements calibrated by pathologists. RESULTS: All three antibodies differentiated six PTEN+ versus six PTEN- cases on external quality assessment. For 138G6 and SP218, high sensitivity and specificity was found for all H-score threshold values including prospectively defined 0, calculated 8 (pathologists), and calculated 5 (computer). High concordance among pathologists in setting computer-based intensities and between pathologists and computer in H-scoring was observed. Because of over-integration of the human eye, pixel-based computer H-scores were overall 54% lower. For all cutoff values, PTEN- was associated with smoking history, squamous cell histology, and higher tumor stage (p < 0.001). In adenocarcinomas, PTEN- was associated with poor survival. CONCLUSION: Calibration of immunoreactivity intensities by pathologists following computerized H-score measurements has the potential to improve reproducibility and homogeneity of biomarker detection regarding epitope validation in multicenter studies.

Continous Rituximab treatment for recurrent diffuse alveolar hemorrhage in a patient with systemic lupus erythematosus and antiphosholipid syndrome.

Diffuse alveolar hemorrhage (DAH) is a rare but potentially fatal complication in systemic lupus erythematosus (SLE). DAH is typically characterized by hemoptysis, dyspnea, new infiltrates on chest x-rays or CT-scans and a drop in hemoglobin. DAH is seen in less than 2% of patients with SLE and carries a high acute mortality risk of up to 70-90%. The current treatment of DAH is high-dose intravenous corticosteroids, cyclophosphamide and extensive supportive care. Plasmapheresis is also often considered in the treatment. A few case reports have described patients with SLE and DAH in whom a single series of Rituximab (RTX), a specific anti-CD20-antigen B-cell antibody, successfully has been used to treat DAH. We here present the first case of a patient with combined SLE, antiphospholipid syndrome (APS) and recurrent DAH who was successfully controlled by continued treatment with RTX.

Introduction of cryobiopsies in the diagnostics of interstitial lung diseases - experiences in a referral center.

Introduction: Transbronchial cryobiopsies (cTBB) has emerged as a new method for obtaining lung tissue biopsies in the diagnosis of interstitial lung diseases (ILDs). Until now, it has been used in a few highly specialized interventional centers and has shown promising results in obtaining a definite diagnosis of ILDs. Method: All patients undergoing a cTBB between November 2015 and June 2016 were included in this case series study. Data on patient demographics, high-resolution computed tomography patterns, size and number of biopsies, histology patterns, the contribution to a confident diagnosis and complications were registered. Results: Thirty-eight patients underwent cTBB in the period. cTBB contributed to the diagnosis in 28 (74%) of the 38 patients. Only few complications were observed; pneumothorax was the most frequent complication (10 patients, 26%). In six patients, local bleeding occurred during the procedure and was easily controlled by a Fogarty catheter balloon and in some cases tranexamic acid. Conclusion: Performing cTBB in the diagnostics of ILDs is a safe and feasible procedure. cTBB resulted in a confident diagnosis in 74% of cases.