MR microscopy to assess clot composition following mechanical thrombectomy predicts recanalization and clinical outcome.

BACKGROUND: Mechanical thrombectomy (MT) is the standard of care for patients with a stroke and large vessel occlusion. Clot composition is not routinely assessed in clinical practice as no specific diagnostic value is attributed to it, and MT is performed in a standardized 'non-personalized' approach. Whether different clot compositions are associated with intrinsic likelihoods of recanalization success or treatment outcome is unknown. METHODS: We performed a prospective, non-randomized, single-center study and analyzed the clot composition in 60 consecutive patients with ischemic stroke undergoing MT. Clots were assessed by ex vivo multiparametric MRI at 9.4 T (MR microscopy), cone beam CT, and histopathology. Clot imaging was correlated with preinterventional CT and clinical data. RESULTS: MR microscopy showed red blood cell (RBC)-rich (21.7%), platelet-rich (white,38.3%) or mixed clots (40.0%) as distinct morphological entities, and MR microscopy had high accuracy of 95.4% to differentiate clots. Clot composition could be further stratified on preinterventional non-contrast head CT by quantification of the hyperdense artery sign. During MT, white clots required more passes to achieve final recanalization and were not amenable to contact aspiration compared with mixed and RBC-rich clots (maneuvers: 4.7 vs 3.1 and 1.2 passes, P<0.05 and P<0.001, respectively), whereas RBC-rich clots showed higher probability of first pass recanalization (76.9%) compared with white clots (17.4%). White clots were associated with poorer clinical outcome at discharge and 90 days after MT. CONCLUSION: Our study introduces MR microscopy to show that the hyperdense artery sign or MR relaxometry could guide interventional strategy. This could enable a personalized treatment approach to improve outcome of patients undergoing MT.

Cartilage damage and bone erosion are more prominent determinants of functional impairment in longstanding experimental arthritis than synovial inflammation.

Chronic inflammation of articular joints causing bone and cartilage destruction consequently leads to functional impairment or loss of mobility in affected joints from individuals affected by rheumatoid arthritis (RA). Even successful treatment with complete resolution of synovial inflammatory processes does not lead to full reversal of joint functionality, pointing to the crucial contribution of irreversibly damaged structural components, such as bone and cartilage, to restricted joint mobility. In this context, we investigated the impact of the distinct components, including synovial inflammation, bone erosion or cartilage damage, as well as the effect of blocking tumor necrosis factor (TNF) on functional impairment in human-TNF transgenic (hTNFtg) mice, a chronic inflammatory erosive animal model of RA. We determined CatWalk-assisted gait profiles as objective quantitative measurements of functional impairment. We first determined body-weight-independent gait parameters, including maximum intensity, print length, print width and print area in wild-type mice. We observed early changes in those gait parameters in hTNFtg mice at week 5 - the first clinical signs of arthritis. Moreover, we found further gait changes during chronic disease development, indicating progressive functional impairment in hTNFtg mice. By investigating the association of gait parameters with inflammation-mediated joint pathologies at different time points of the disease course, we found a relationship between gait parameters and the extent of cartilage damage and bone erosions, but not with the extent of synovitis in this chronic model. Next, we observed a significant improvement of functional impairment upon blocking TNF, even at progressed stages of disease. However, blocking TNF did not restore full functionality owing to remaining subclinical inflammation and structural microdamage. In conclusion, CatWalk gait analysis provides a useful tool for quantitative assessment of functional impairment in inflammatory destructive arthritis. Our findings indicate that cartilage damage and bone erosion, but not synovial inflammation, are the most important determinants for progressive functional impairment in this chronic erosive arthritis model.

Lipocalin-like prostaglandin D synthase (L-PGDS) concentration in aqueous humour in patients with open-angle glaucoma.

PURPOSE: To report on the concentration of lipocalin-like prostaglandin D synthase (L-PGDS) in the aqueous humour (AH) in patients with open-angle glaucoma (OAG). PATIENTS AND METHODS: Prospective assessment in 20 patients (13 female, 7 male, mean age 74±10.6 y) who underwent surgery for OAG. AH was sampled and analyzed for L-PGDS concentration. AH from 26 patients (11 female, 15 male, 72.4±14.4 y) without glaucoma who underwent cataract surgery, served as control subjects. RESULTS: The L-PGDS concentration in the AH sampled from the anterior chamber in the OAG group (5.9±2.4 mg/L) was significantly (P<0.001) higher than in the control group (3.3±1.3 mg/L). There were no significant differences between the concentrations of L-PGDS between the left and the right eye or between genders. CONCLUSIONS: L-PGDS concentration in the AH of patients with OAG was significantly elevated compared with its concentration in the AH of nonglaucomatous eyes. As L-PGDS is a biologically pluripotent protein, its possible role in glaucoma warrants further examination.

Metastatic patterns at autopsy in patients with ovarian carcinoma.

BACKGROUND: Previously published studies concerning autopsy findings in ovarian cancer failed to consider the broad differences in factors that influence the course of disease. Furthermore, those studies were conducted when the currently accepted standards in diagnostics and therapy had not been fully established. The objective of the current study was to determine the frequency and sites of metastases in patients with ovarian cancer with particular attention to the clinical course and therapy. METHODS: Autopsy reports, histologic slides, and clinical files from 197 patients who died of ovarian carcinoma between 1975 and 2005 were studied. The distribution of metastatic sites (19 different organ sites) and metastatic patterns, with particular attention to clinical course (age, length of survival) and therapy (surgical treatment with curative intention, different chemotherapy regimens), were analyzed. RESULTS: Overall, 66.3% of patients had metastases to sites outside the abdominopelvic cavity. Patients who were aged >70 years, who had a disease duration