Finding Needles in the Haystack: Identifying Patients with Rare Subtype of Multiple Myeloma Supported by a Data Warehouse and Information Extraction.

Finding patient cases with extremely rare pathologies is a laborious task. To decrease time spent on manually searching through thousands of discharge letters and reports, a data warehouse with a fast fulltext search index was queried. Our use case is to find "macrofocal myeloma", i.e. Multiple Myeloma patients with few large lesions. We guessed the number of those patients in the University Hospital Würzburg at about 20. Most criteria were available in the data warehouse in an unstructured form requiring information extraction. 8 patient cases were found by searching for different spellings of "macrofocal myeloma" in discharge letters directly. With an indirect search combining several criteria, we found additional 23 candidate patient cases, from which 10 were classified by a domain expert as correct. The most difficult criteria were determining the degree of bone marrow infiltration. We achieved an F1 score of 93.2 % for this task. The number of patient cases to be screened manually for this disease decreased from about 25000 to 23.

Perivascular Perfusion on Contrast-Enhanced Ultrasound (CEUS) Is Associated with Inflammation in Patients with Acute Deep Vein Thrombosis.

Background Inflammatory processes of the venous wall in acute deep vein thrombosis (DVT) play a role in thrombus formation and resolution. However, direct evaluation of the perivascular inflammation is currently not feasible. Objective To assess perivascular perfusion in acute proximal DVT using contrast-enhanced ultrasound (CEUS) reflecting perivenous inflammation and its association with systemic inflammatory markers in a single-centre, prospective observational study. Patients/Methods Twenty patients with proximal DVT underwent CEUS imaging in the thrombosed and contralateral popliteal vein at baseline and after 2 weeks and 3 months. Perfusion was quantified by measuring peak enhancement (PE) and wash-in rate (WiR) in a perivenous region after bolus injection of the contrast agent. High-sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6) were determined at the time of each CEUS imaging. Results PE and WiR were significantly higher in the thrombosed compared with the unaffected leg at baseline (1,007 vs. 34 au and 103 vs. 4 au/s) and 2-week follow-up (903 vs. 35 au and 70 vs. 4 au/s). Compared with baseline, PE and WiR in the thrombosed leg significantly decreased to 217 au and 18 au/s at 3-month follow-up.At baseline, hsCRP and IL-6 were elevated at 20.1 mg/mL and 8.2 pg/mL and decreased significantly to 2.8 mg/mL and 2.6 pg/mL at 2-week follow-up, remaining low after 3 months. There was a weak association between the level of inflammatory markers and the CEUS parameters at baseline on the thrombosed leg. Conclusion Elevated perivascular perfusion assessed by CEUS imaging is associated with the inflammatory response in acute DVT.

Inositol 1,4,5-trisphosphate-mediated sarcoplasmic reticulum-mitochondrial crosstalk influences adenosine triphosphate production via mitochondrial Ca2+ uptake through the mitochondrial ryanodine receptor in cardiac myocytes.

AIMS: Elevated levels of inositol 1,4,5-trisphosphate (IP3) in adult cardiac myocytes are typically associated with the development of cardiac hypertrophy, arrhythmias, and heart failure. IP3 enhances intracellular Ca(2+ )release via IP3 receptors (IP3Rs) located at the sarcoplasmic reticulum (SR). We aimed to determine whether IP3-induced Ca(2+ )release affects mitochondrial function and determine the underlying mechanisms. METHODS AND RESULTS: We compared the effects of IP3Rs- and ryanodine receptors (RyRs)-mediated cytosolic Ca(2+ )elevation achieved by endothelin-1 (ET-1) and isoproterenol (ISO) stimulation, respectively, on mitochondrial Ca(2+ )uptake and adenosine triphosphate (ATP) generation. Both ET-1 and isoproterenol induced an increase in mitochondrial Ca(2+ )(Ca(2 +) m) but only ET-1 led to an increase in ATP concentration. ET-1-induced effects were prevented by cell treatment with the IP3 antagonist 2-aminoethoxydiphenyl borate and absent in myocytes from transgenic mice expressing an IP3 chelating protein (IP3 sponge). Furthermore, ET-1-induced mitochondrial Ca(2+) uptake was insensitive to the mitochondrial Ca(2+ )uniporter inhibitor Ru360, however was attenuated by RyRs type 1 inhibitor dantrolene. Using real-time polymerase chain reaction, we detected the presence of all three isoforms of IP3Rs and RyRs in murine ventricular myocytes with a dominant presence of type 2 isoform for both receptors. CONCLUSIONS: Stimulation of IP3Rs with ET-1 induces Ca(2+ )release from the SR which is tunnelled to mitochondria via mitochondrial RyR leading to stimulation of mitochondrial ATP production.

Contrast-enhanced ultrasound: clinical applications in patients with atherosclerosis.

Contrast-enhanced ultrasound (CEUS) is increasingly being used to evaluate patients with known or suspected atherosclerosis. The administration of a microbubble contrast agent in conjunction with ultrasound results in an improved image quality and provides information that cannot be assessed with standard B-mode ultrasound. CEUS is a high-resolution, noninvasive imaging modality, which is safe and may benefit patients with coronary, carotid, or aortic atherosclerosis. CEUS allows a reliable assessment of endocardial borders, left ventricular function, intracardiac thrombus and myocardial perfusion. CEUS results in an improved detection of carotid atherosclerosis, and allows assessment of high-risk plaque characteristics including intraplaque vascularization, and ulceration. CEUS provides real-time bedside information in patients with a suspected or known abdominal aortic aneurysm or aortic dissection. The absence of ionizing radiation and safety of the contrast agent allow repetitive imaging which is particularly useful in the follow-up of patients after endovascular aneurysm repair. New developments in CEUS-based molecular imaging will improve the understanding of the pathophysiology of atherosclerosis and may in the future allow to image and directly treat cardiovascular diseases (theragnostic CEUS). Familiarity with the strengths and limitations of CEUS may have a major impact on the management of patients with atherosclerosis.

Contrast-enhanced ultrasound after endovascular aortic repair-current status and future perspectives.

An increasing number of patients with abdominal aortic aneurysms (AAAs) are undergoing endovascular aortic repair (EVAR) instead of open surgery. These patients require lifelong surveillance, and the follow-up imaging modality of choice has been traditionally computed tomography angiography (CTA). Repetitive CTA imaging is associated with cumulative radiation exposure and requires the administration of multiple doses of nephrotoxic contrast agents. Contrast-enhanced ultrasound (CEUS) has emerged as an alternative strategy in the follow-up of patients with EVAR and demonstrates high sensitivity and specificity for detection of endoleaks. In fact, a series of studies have shown that CEUS is at least performing equal to computed tomography for the detection and classification of endoleaks. This article summarizes current evidence of CEUS after EVAR and demonstrates its usefulness via various patient cases.

Long term follow-up after endovascular brachytherapy of femoro-popliteal arteries.

To perform a long term follow-up after endovascular brachytherapy (EVBT) and balloon angioplasty (PTA) regarding vessel patency and diameter. EVBT had been successfully used to decrease restenosis in short term, but long term data are lacking. Participants of a randomized study comparing EVBT and balloon angioplasty alone were invited for follow-up examination ten years after intervention. Using a standardized protocol measurement of the patency and vessel diameter was performed of femoral and popliteal arteries. 44 patients were included, 21 had been treated with EVBT and 23 had received PTA alone. Target lesion patency was similar between the two groups (90.5% vs. 87.0%). Vessel diameter of the target lesion was significantly greater in the EVBT group (6.4 mm, range 3.9-9.9) compared to the controls (5.0 mm, range 3.1-7.4; p = 0.002). Ten years after EVBT of femoro-popliteal arteries vessel diameter is significantly increased whereas patency rate is not different compared to angioplasty alone.

Endovascular treatment for extensive aortoiliac artery reconstruction: a single-center experience based on 1712 interventions.

PURPOSE: To determine the clinical and technical outcomes following endovascular therapy for aortoiliac occlusive disease, including complex reconstruction of the aortic bifurcation. METHODS: A retrospective database search identified 1184 consecutive patients (864 men; mean age 64±10 years) who underwent 1712 procedures to treat target lesions in the distal aorta and iliac arteries from September 1996 to December 2006. The intended strategy was to open only one femoral access site primarily, so a second puncture was needed only for the kissing balloon technique at the aortic bifurcation. The primary endpoint was a 1-year duplex-based primary patency; secondary endpoints included acute technical success (residual stenosis <30%), secondary patency, and target lesion revascularization (TLR). Results were stratified by lesion morphology, which was classified according to the TransAtlantic Inter-Society Consensus (TASC II) document. RESULTS: Most of the interventions were done in the iliac arteries (n=1337); 292 cases involved the aortic bifurcation, and 83 cases were in the distal aorta/aortic bifurcation. The mean follow-up was 3.24 years (range 0-12.7). In the entire study cohort, the 12- and 24-month restenosis, TLR, and primary/secondary patency rates did not differ among TASC II A-D subgroups. The symptom-driven TLR in the entire cohort was 8% and 9% at the 12- and 24-month follow-up, leading to secondary patency rates of 96% and 91% in the entire cohort. Outcomes for complex interventions in the distal aorta or aortic bifurcation did not differ significantly compared to the total cohort. The overall survival without restenosis, amputation, or surgery in TASC II subgroups A+B was higher (69.6%±1.5%) compared to TASC II C+D lesions (62.8%±1.9%, p=0.001). CONCLUSION: The indication for percutaneous intervention in aortoiliac occlusive disease can be extended to complex TASC C and D lesions in experienced endovascular centers, even if complex reconstruction of the distal aorta or the aortic bifurcation is indicated.

Differences in coronary artery plaques between target and non-target vessels.

OBJECTIVE: We used intravascular ultrasound (IVUS) and virtual histology (VH) to assess the differences of plaque burden and composition between target coronary arteries containing the culprit lesion and non-target coronary arteries. METHODS: Sixty patients referred for acute (n = 19) or elective (n = 41) coronary angiography were included. The target vessel containing the culprit lesion was identified by angiography. A non-target coronary artery was chosen for comparison. The first 4 cm of each vessel were analyzed with IVUS and VH. RESULTS: Total plaque burden was higher in the target vessel compared to the non-target vessel (52.4% vs. 45.9%, a relative difference of 14.2%; p < 0.001). The plaque composition of the target vessel correlated strongly with the plaque composition of the non-target vessel, but the relative amount of necrotic core was significantly higher in the target vessels (21.7% vs 19.2%; p = 0.028), whereas the amount of fibrolipidic material was significantly greater in non-target vessels (10.6% vs. 12.7%; p = 0.035). CONCLUSIONS: We conclude that in patients with relevant coronary artery disease, plaque burden and the amount of necrotic core material are greater in the target vessel. There is a strong correlation of plaque composition between target and non-target coronary arteries.

Different vascular smooth muscle cell apoptosis in the human internal mammary artery and the saphenous vein. Implications for bypass graft disease.

BACKGROUND: The remarkable patency of internal mammary artery (MA) grafts compared to saphenous vein (SV) grafts has been related to different biological properties of the two blood vessels. We examined whether proliferation and apoptosis of vascular smooth muscle cells (VSMC) from human coronary artery bypass vessels differ according to patency rates. METHODS AND RESULTS: Proliferation rates to serum or platelet-derived growth factor (PDGF)-BB were lower in VSMC from MA than SV. Surface expression of PDGF beta-receptor was slightly lower, while that of alpha-receptor was slightly higher in MA than SV. Cell cycle distribution, expression of cyclin E, cdk2, p21, p27, p57, and cdk2 kinase activity were identical in PDGF-BB-stimulated cells from MA and SV. However, apoptosis rates were higher in MA than SV determined by lactate dehydrogenase release, DNA fragmentation, and Hoechst 33258 staining. Moreover, caspase inhibitors (Z-VAD-fmk, Boc-D-fmk) abrogated the different proliferation rates of VSMC from MA versus SV. Western blotting and GSK3-beta kinase assay revealed lower Akt activity in VSMC from MA versus SV, while total Akt expression was identical. Adenoviral transduction of a constitutively active Akt mutant abrogated the different proliferation rates of VSMC from MA versus SV. CONCLUSIONS: Higher apoptosis rates due to lower Akt activity rather than different cell cycle regulation account for the lower proliferation of VSMC from MA as compared to SV. VSMC apoptosis may protect MA from bypass graft disease.