Sarcoidosis, alveolar β-actin and pulmonary fibrosis

BACKGROUND: Sarcoidosis is a multisystem granulomatous disease of unknown aetiology. Proteins present within the alveolar space early in sarcoidosis disease may provide an insight into novel mechanisms for the development of fibrotic disease and in particular pulmonary fibrosis.

METHODS: A modified two-dimensional difference gel electrophoresis protocol was applied to the human bronchoalveolar lavage fluid (hBALF) of four patients with non-persistent pulmonary interstitial disease at 4-year follow-up (defined as mild disease) and four patients who developed pulmonary interstitial disease at 4-year follow-up (defined as severe disease). The protein β-actin was identified by LC-MS/MS from a preparative gel and found to be significantly elevated in early lavages from the severe disease group. To look at the potential pro-fibrotic effects of this protein, primary human pulmonary fibroblasts (CCD-19Lu) were treated with recombinant β-actin following which qPCR and ELISA assays were used to measure any effects.

RESULTS: We found that β-actin levels were significantly elevated in early hBALF samples in patients who subsequently developed severe disease when compared to the mild group. Treating primary human pulmonary fibroblasts with recombinant β-actin led to enhanced gene expression of the pro-fibrotic markers alpha smooth muscle actin and collagen 1 as well as the increased secretion of interleukin-13 and metalloproteinases 3 and 9.

CONCLUSION: Free β-actin within the lungs of sarcoidosis patients potentially may contribute to disease pathogenesis particularly in the context of abnormal remodelling and the development of pulmonary fibrosis.

Primary pulmonary myxoid sarcoma with EWSR1-CREB1 fusion: a new tumor entity.

We present clinicopathologic data on 10 pulmonary myxoid sarcomas, which are defined by distinctive histomorphologic features and characterized by a recurrent fusion gene, that appear to represent a distinct tumor entity at this site. The patients [7 female, 3 male; aged 27 to 67 y (mean, 45 y)] presented with local or systemic symptoms (n=5), symptoms from cerebral metastasis (1), or incidentally (2). Follow-up of 6 patients showed that 1 with brain metastasis died shortly after primary tumor resection, 1 developed a renal metastasis but is alive and well, and 4 are disease free after 1 to 15 years. All tumors involved pulmonary parenchyma, with a predominant endobronchial component in 8 and ranged from 1.5 to 4 cm. Microscopically, they were lobulated and composed of cords of polygonal, spindle, or stellate cells within myxoid stroma, morphologically reminiscent of extraskeletal myxoid chondrosarcoma. Four cases showed no or minimal atypia, 6 showed focal pleomorphism, and 5 had necrosis. Mitotic indices varied, with most tumors not exceeding 5/10 high-power fields. Tumors were immunoreactive for only vimentin and weakly focal for epithelial membrane antigen. Of 9 tumors, 7 were shown to harbor a specific EWSR1-CREB1 fusion by reverse transcription-polymerase chain reaction and direct sequencing, with 7 of 10 showing EWSR1 rearrangement by fluorescence in situ hybridization. This gene fusion has been described previously in 2 histologically and behaviorally different sarcomas: clear cell sarcoma-like tumors of the gastrointestinal tract and angiomatoid fibrous histiocytomas; however, this is a novel finding in tumors with the morphology we describe and that occur in the pulmonary region.

Visual functioning and health-related quality of life in diabetic patients about to undergo anti-vascular endothelial growth factor treatment for sight-threatening macular edema

Purpose To examine patient-reported outcome (PRO) in a selected group of Swedish patients about to receive anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). Material and methods In this cross-sectional study, 59 patients with diabetes mellitus, who regularly visited the outpatient eye-clinics, were included. Sociodemographic and clinical data were collected and the patients completed PRO measures before starting anti-VEGF treatment. PRO measures assessed eye-specific outcomes (NEI-VFQ-25) and generic health-related quality of life (SF-36). Results The participants consisted of 30 men and 29 women (mean age, 68.5 years); 54 (92 %) patients had type 2 diabetes; Five (9%) patients had moderate or severe visual impairment; 28 (47 %) were classified as having mild visual impairment. Some of the patients reported overall problems in their daily lives, such as with social relationships, as well as problems with impaired sight as a result of reduced distance vision. Conclusions Further studies are needed to investigate PRO factors related to low perceived general health in this patient population. It is important to increase our understanding of such underlying mechanisms to promote improvements in the quality of patient care.

Anti-VEGF treatment of patients with diabetic macular edema : Studies of visual acuity, macular edema and patient-reported outcomes

The aim of this thesis was to describe and evaluate visual acuity, macular edema and patientreported outcomes (PRO) following anti-VEGF treatment of diabetic macular edema (DME) patients in a real-world setting. Using a longitudinal study design, a cohort of DME patients was followed from baseline to 1 year after treatment start. Data were collected from two eye clinics at two county hospitals. Social background characteristics, medical data and PRO were measured before treatment initiation, at four month and after 1 year. A total of 57 patients completed the study. Mean age was 69 years and the sample was equally distributed regarding sex. At baseline, the patients described their general health as low. One year after treatment initiation, 30 patients had improved visual acuity and 27 patients had no improvement in visual acuity. The patients whose visual acuity improved reported an improvement in several subscales in patient-reported outcome measures (PROM), which was in contrast to the group that experienced a decline in visual acuity, where there was no improvement in PROM. Outcomes from the study can be useful for developing and providing relevant information and support to patients undergoing this treatment.

Patient-reported outcomes and visual acuity after 12 months of anti-VEGF-treatment for sight-threatening diabetic macular edema in a real world setting

Aims To examine objective visual acuity measured with ETDRS, retinal thickness (OCT), patient reported outcome and describe levels of glycated hemoglobin and its association with the effects on visual acuity in patients treated with anti-VEGF for visual impairment due to diabetic macular edema (DME) during 12 months in a real world setting. Methods In this cross-sectional study, 58 patients (29 females and 29 males; mean age, 68 years) with type 1 and type 2 diabetes diagnosed with DME were included. Medical data and two questionnaires were collected; an eye-specific (NEI VFQ-25) and a generic health-related quality of life questionnaire (SF-36) were used. Results The total patient group had significantly improved visual acuity and reduced retinal thickness at 4 months and remains at 12 months follow up. Thirty patients had significantly improved visual acuity, and 27 patients had no improved visual acuity at 12 months. The patients with improved visual acuity had significantly improved scores for NEI VFQ-25 subscales including general health, general vision, near activities, distance activities, and composite score, but no significant changes in scores were found in the group without improvements in visual acuity. Conclusions Our study revealed that anti-VEGF treatment improved visual acuity and central retinal thickness as well as patient-reported outcome in real world 12 months after treatment start.

Free-Floating Thrombi in the Right Atrium Causing Pulmonary Embolism

A 74-year-old man presented to our Emergency Department with acute dyspnoea. His electrocardiogram showed atrial flutter with 2:1 block and a rate of 150 bpm. Initial investigations revealed a D-dimer level of 6.01 mg/dl. Based on the patient’s complaints and the high D-dimer level, computed tomography pulmonary angiography was immediately performed. This showed no evidence of pulmonary embolism, but there were pneumatic changes in the right upper lung lobe. Antibiotics treatment was started with pipracillin/tazobactam, after which the patient’s condition improved. However, on the third day after admission he developed acute dyspnoea, diaphoresis and cardiopulmonary instability immediately after defecation. To promptly confirm our clinical suspicion of pulmonary embolism, a transthoracic echocardiography was carried out. This demonstrated a worm-like, mobile mass in the right heart. The right ventricle was enlarged, and paradoxical septal motion was present, indicating right ventricular pressure overload. The systolic tricuspid valvular gradient was 56 mmHg. The patient was treated with thrombolysis. His condition was greatly clinically improved after 3 hours. After 10 days of hospitalization, the patient was discharged.