Trochanter migrans: late complications due to displacement of the lesser trochanter in trochanteric fractures.

Complications associated with secondary displacement and migration of the lesser trochanter fragment in trochanteric fractures are rare. The complaints expressed by the patient may be misunderstood and attributed to implant-associated or patient-specific problems likely to occur after surgery. This series illustrates potentially dangerous late complications caused by secondary migration of the lesser trochanter. It may help focus the surgeon's attention on possible functional impairment and severe late complications caused by displacement of the lesser trochanter in trochanteric fractures that require prompt intervention.

Longitudinal imaging of T cell-based immunotherapy with multi-spectral, multi-scale optoacoustic tomography.

Most imaging studies of immunotherapy have focused on tracking labeled T cell biodistribution in vivo for understanding trafficking and homing parameters and predicting therapeutic efficacy by the presence of transferred T cells at or in the tumour mass. Conversely, we investigate here a novel concept for longitudinally elucidating anatomical and pathophysiological changes of solid tumours after adoptive T cell transfer in a preclinical set up, using previously unexplored in-tandem macroscopic and mesoscopic optoacoustic (photoacoustic) imaging. We show non-invasive in vivo observations of vessel collapse during tumour rejection across entire tumours and observe for the first time longitudinal tumour rejection in a label-free manner based on optical absorption changes in the tumour mass due to cellular decline. We complement these observations with high resolution episcopic fluorescence imaging of T cell biodistribution using optimized T cell labeling based on two near-infrared dyes targeting the cell membrane and the cytoplasm. We discuss how optoacoustic macroscopy and mesoscopy offer unique contrast and immunotherapy insights, allowing label-free and longitudinal observations of tumour therapy. The results demonstrate optoacoustic imaging as an invaluable tool in understanding and optimizing T cell therapy.

Correction to: In vivo imaging of early stages of rheumatoid arthritis by α5ß1-integrin-targeted positron emission tomography.

Following publication of the original article [1], the authors have reported an error in the 'Histopathology' (under 'Materials and methods') section of the article that compromises the reproducibility of the paper.

In vivo imaging of early stages of rheumatoid arthritis by α5ß1-integrin-targeted positron emission tomography.

BACKGROUND: Rheumatoid arthritis (RA) is one of the most common rheumatic diseases. Joint inflammation and pathological growth of joint cartilage cause swollen and painful joints, which severely diminishes the patients' life quality. There is no causal treatment. Symptomatic therapies should start as early as possible to take maximal effect. Hence, diagnostic procedures capable of detecting affected joints before the onset of clinical symptoms are highly desirable. We explored the value of PET imaging of integrin subtypes αvß3 and α5ß1 for early detection of RA foci in collagen-induced arthritis (CIA) mouse models. RESULTS: Development of RA in CIA mice was monitored by paw scoring, and αvß3- and α5ß1-integrin expression was quantified by µPET using 68Ga-Avebetrin and 68Ga-Aquibeprin. For consecutive sections of selected decalcified joints (knee, ankle), arthritic degeneration and integrin expression were assessed by MOVAT staining and ß3/α5 immunohistochemistry (IHC), respectively. ß3- and α5-IHC revealed elevated levels of both αvß3- and α5ß1-integrin in arthritic joints. Unlike αvß3, α5ß1 is strongly expressed in the proliferating synovial lining layer, which suggests that its presence is directly related to RA development. For mice with advanced RA (6 weeks after CIA), PET signals for α5ß1-integrin were substantially stronger (> 300% of baseline) than that of αvß3-integrin (< 200%). A longitudinal PET follow-up revealed that the manifestation of clinical symptoms of RA is preceded by upregulation of α5ß1- but not of αvß3-integrin. CONCLUSION: α5ß1-integrin PET could add a new functional imaging aspect to the portfolio of RA diagnostics because it appears to be a sensitive biomarker for early RA development. We suggest α5ß1-integrin PET as a valuable tool to achieve a higher precision for early diagnosis of RA, including initial staging, monitoring of the disease course, and drug treatment, and for planning of radiosynoviorthesis (RSO).

SNR analysis of contrast-enhanced MR imaging for early detection of rheumatoid arthritis.

OBJECTIVE: To investigate whether signal to noise (SNR) analysis of contrast-enhanced MRI gives additional benefit for early disease detection by Magnetic Resonance Imaging (MRI) of experimental rheumatoid arthritis (RA) in a small animal model. METHODS: We applied contrast-enhanced MRI at 7T in DBA mice with or without collagen-induced arthritis (CIA). Clinical score, OMERACT RAMRIS analysis and analysis of signal to noise ratios (SNR) of regions of interest in RA bearing mice, methotrexate/methylprednisolone acetate treated RA and control animals were compared with respect to benefit for early diagnosis. RESULTS: While treated RA and control animals did not show signs of RA activity in any of the above-mentioned scoring methods at any time point analyzed, RA animals revealed characteristic signs of RA in RAMRIS at the same time point when RA was detected clinically through scoring of the paws. The MR-based SNR analysis detected signs of synovitis, the earliest indication of RA, not only in late clinical stages, but also at an early stage when little or no clinical signs of RA were present in CIA animals and RAMRIS did not allow a distinct early detection. CONCLUSION: SNR analysis of contrast-enhanced MR imaging provides additional benefit for early arthritis detection in CIA mice.

Coronal oblique orientation of the neural foramen improves cervical spine MRI: A comparison of the sensitivity of different angulations.

OBJECTIVE: Angulated projections are used in radiography to show the cervical neural foramen. Imaging the coronal oblique planes in an MRI of the cervical spine should therefore improve visualization of neural foramen pathology. This has to be demonstrated. PATIENTS AND METHODS: A multi-center investigation of 40 patients with monoradiculopathy and 10 healthy controls was undertaken. T2-weighted sagittal, coronal oblique and axial slices were individually and separately examined by four readers blinded to the diagnosis. The statistical evaluation compared against the clinical gold standard of the neurological diagnosis of a single nerve root irritation or lesion. RESULTS: The sensitivity/specificity required to detect the relevant neural foramen pathology was 0.47/0.60 for axial, 0.57/0.90 for sagittal and 0.55/0.70 for coronal oblique scans. The readers felt significantly more confident in attributing the cause of pathology using coronal oblique planes. Interreader reliability was moderate to substantial, with the highest values for the sagittal planes (0.39-0.76) and lower values for the transversal and coronal oblique planes (0.15-0.63). Intrareader reliability was substantial, with values between 0.53 and 0.88. Reading the axial planes was significantly more time consuming than reading the other planes. CONCLUSION: The use of coronal oblique planes in cervical spine MRIs increases sensitivity and confidence in attributing the cause of neural foramen obstruction. They are easy to interpret and demand less reading time than axial planes, and so the inclusion of coronal oblique planes in the workup of cervical spine MRI is recommended, at least when neural foramen pathology is suspected.

Noninvasive quantitative assessment of microcirculatory disorders of the upper extremities with 2D fluorescence optical imaging.

BACKGROUND: Quantitative Imaging of microcirculatory disorders is challenging. OBJECTIVE: To investigate the feasibility of 2D Fluorescence Optical Imaging (FOI) for characterization and quantification of microcirculatory disorders in peripheral arterial occlusive disease (PAOD) of the upper extremity. METHODS: 9 patients with various clinical presentations of PAOD of the upper extremity were included. Quantitative analysis of both hands was performed by assessing the fluorescence intensity of Indocyanine Green (ICG) dynamically over a time period of 360 seconds. Analysis of the signal intensity within multiple regions of both hands was calculated and time-dependent perfusion curves for each region of interest were plotted over time. RESULTS: Compared to the healthy, vascular non-impaired segments, pathological segments with an impaired tissue perfusion were identified through a decreased rate of early tissue enhancement (p = 0.02) and increased signal intensity of the optical perfusion agent per second (p < 0.001). The affected segments showed a decreased maximum signal intensity and a prolonged interval to reach the maximum signal intensity (time to peak). CONCLUSION: 2D FOI allows quantitative assessment of the peripheral microcirculation in various vascular pathophysiologies and is able to detect the impaired tissue perfusion in patients with vascular disorders of the upper extremity.

[Chances and Risks of Telemedicine in Orthopaedics and Trauma Surgery]. / Chancen und Risiken der Telemedizin in der Orthopädie und Unfallchirurgie.

BACKGROUND: The use of information technology (IT) in health care has continuously increased. This includes software solutions for digitalisation, data storage and innovative approaches in diagnostics. The facilitation of the access to specific information, even by the patient, has changed daily clinical work. Patients inform themselves about symptoms, diagnostic methods and treatment options. This urge for information and the wish for the best treatment is summarised in the expression "patient empowerment". In some countries, the gap between do-it-yourself diagnosis and telemedicine via the telephone has already been closed. A sophisticated telemedical hotline may help to improve consultation and treatment of patients living in remote regions or rural communities. Traumatology telemedicine may also be used in trauma environments, such as disasters or mass casualties. Therefore, the purpose of this study was to assess the demand for e-health solutions among patients seeking the help of the emergency department in a trauma hospital. METHODS: A total of 255 patients (age range 18 - 75 years) were included in the study and were surveyed with the use of a questionnaire. As regards personal data, the questionnaire asked the patient about their Internet habits and about interesting topics they had researched in the world wide web. However, the questionnaire was specifically designed to ask for potential benefits and the patient's expectations for e-health solutions. Expected weaknesses and procedures for telemedical services were also included in a subsection. RESULTS: 43.5% of the patient cohort were woman and 56.5% men. The average distance to the hospital was 39.86 km. 223 patients were insured by the governmental health service providers and 32 had private insurance coverage. Aside from online shopping and online banking, the search for health topics was most frequent. The greatest fear was the lack of personal contact to the doctor (71.2%). Patients were also concerned about the safety of individual health data in privately run databanks (54.3%). On the other hand, patients were neutral towards the web-based scheduling of medical appointments. Automatic reminders for such appointments were desired via e-mail (68.8%) or SMS (66.5%). CONCLUSION: Patients are demanding mobile solutions for scheduling medical appointments, including reminders of these. Patients are keen to be involved in the communications and would like to receive overall information about their health status. Online chats or video calls with physicians are not their first choice but might be a possibility until personal presentation.

Diagnostic value of MRI-based 3D texture analysis for tissue characterisation and discrimination of low-grade chondrosarcoma from enchondroma: a pilot study.

OBJECTIVES: To explore the diagnostic value of MRI-based 3D texture analysis to identify texture features that can be used for discrimination of low-grade chondrosarcoma from enchondroma. METHODS: Eleven patients with low-grade chondrosarcoma and 11 patients with enchondroma were retrospectively evaluated. Texture analysis was performed using mint Lesion: Kurtosis, entropy, skewness, mean of positive pixels (MPP) and uniformity of positive pixel distribution (UPP) were obtained in four MRI sequences and correlated with histopathology. The Mann-Whitney U-test and receiver operating characteristic (ROC) analysis were performed to identify most discriminative texture features. Sensitivity, specificity, accuracy and optimal cut-off values were calculated. RESULTS: Significant differences were found in four of 20 texture parameters with regard to the different MRI sequences (p<0.01). The area under the ROC curve values to discriminate chondrosarcoma from enchondroma were 0.876 and 0.826 for kurtosis and skewness in contrast-enhanced T1 (ceT1w), respectively; in non-contrast T1, values were 0.851 and 0.822 for entropy and UPP, respectively. The highest discriminatory power had kurtosis in ceT1w with a cut-off ≥3.15 to identify low-grade chondrosarcoma (82 % sensitivity, 91 % specificity, accuracy 86 %). CONCLUSION: MRI-based 3D texture analysis might be able to discriminate low-grade chondrosarcoma from enchondroma by a variety of texture parameters. KEY POINTS: • MRI texture analysis may assist in differentiating low-grade chondrosarcoma from enchondroma. • Kurtosis in the contrast-enhanced T1w has the highest power of discrimination. • Tools provide insight into tumour characterisation as a non-invasive imaging biomarker.

Characterization of Cardiac Dynamics in an Acute Myocardial Infarction Model by Four-Dimensional Optoacoustic and Magnetic Resonance Imaging.

Extraction of murine cardiac functional parameters on a beat-by-beat basis is limited with the existing imaging modalities due to insufficient three-dimensional temporal resolution. Faster volumetric imaging methods enabling in vivo characterization of functional parameters are poised to advance cardiovascular research and provide a better understanding of the mechanisms underlying cardiac diseases. We present a new approach based on analyzing contrast-enhanced optoacoustic (OA) images acquired at high volumetric frame rate without using cardiac gating or other approaches for motion correction. We apply an acute murine myocardial infarction model optimized for acquisition of artifact-free optoacoustic imaging data to study cardiovascular hemodynamics. Infarcted hearts (n = 21) could be clearly differentiated from healthy controls (n = 9) based on a significantly higher pulmonary transit time (PTT) (2.25 [2.00-2.41] s versus 1.34 [1.25-1.67] s, p = 0.0235), while no statistically significant difference was observed in the heart rate (318 [252-361] bpm versus 264 [252-320] bpm, p = 0.3129). Nevertheless, nonlinear heartbeat dynamics was stronger in the healthy hearts, as evidenced by the third harmonic component in the heartbeat spectra. MRI data acquired from the same mice further revealed that the PTT increases with the size of infarction and similarly increases with reduced ejection fraction. Moreover, an inverse relationship between infarct PTT and time post-surgery was found, which suggests the occurrence of cardiac healing. In combination with the proven ability of optoacoustics to track targeted probes within the injured myocardium, our method can depict cardiac anatomy, function, and molecular signatures, with both high spatial and temporal resolution. Volumetric four-dimensional optoacoustic characterization of cardiac dynamics with supreme temporal resolution can capture cardiovascular dynamics on a beat-by-beat basis in mouse models of myocardial ischemia.

Multispectral Optoacoustic Tomography (MSOT) of Human Breast Cancer.

Purpose: In a pilot study, we introduce fast handheld multispectral optoacoustic tomography (MSOT) of the breast at 28 wavelengths, aiming to identify high-resolution optoacoustic (photoacoustic) patterns of breast cancer and noncancerous breast tissue.Experimental Design: We imaged 10 female patients ages 48-81 years with malignant nonspecific breast cancer or invasive lobular carcinoma. Three healthy volunteers ages 31-36 years were also imaged. Fast-MSOT was based on unique single-frame-per-pulse (SFPP) image acquisition employed to improve the accuracy of spectral differentiation over using a small number of wavelengths. Breast tissue was illuminated at the 700-970 nm spectral range over 0.56 seconds total scan time. MSOT data were guided by ultrasonography and X-ray mammography or MRI.Results: The extended spectral range allowed the computation of oxygenated hemoglobin (HBO2), deoxygenated hemoglobin (HB), total blood volume (TBV), lipid, and water contributions, allowing first insights into in vivo high-resolution breast tissue MSOT cancer patterns. TBV and Hb/HBO2 images resolved marked differences between cancer and control tissue, manifested as a vessel-rich tumor periphery with highly heterogeneous spatial appearance compared with healthy tissue. We observe significant TBV variations between different tumors and between tumors over healthy tissues. Water and fat lipid layers appear disrupted in cancer versus healthy tissue; however, offer weaker contrast compared with TBV images.Conclusions: In contrast to optical methods, MSOT resolves physiologic cancer features with high resolution and revealed patterns not offered by other radiologic modalities. The new features relate to personalized and precision medicine potential. Clin Cancer Res; 23(22); 6912-22. ©2017 AACR.

Fluorescence optical imaging and 3T-MRI for detection of synovitis in patients with rheumatoid arthritis in comparison to a composite standard of reference.

OBJECTIVES: To address whether Indocyanine Green (ICG) enhanced fluorescence optical imaging (FOI) is more sensitive than magnetic resonance imaging (MRI) in the detection of synovitis of the wrist and finger joints in rheumatoid arthritis and to analyze the performance of FOI depending on the grade of synovitis. METHODS: Twenty patients with highly active rheumatoid arthritis (mean DAS28-ESR 5.25±1.0) and thirteen healthy volunteers underwent clinical examination, FOI and contrast-enhanced 3T-MRI. Joints were rated by three independent readers semiquantitatively (grade 0-3: no, low, moderate and high grade synovitis) and compared to a semiquantitative composite standard of reference (cSOR, grade 0-3) that incorporated clinical parameters, FOI and MRI results. RESULTS: 2.868 evaluations in 956 joints were performed. FOI had an overall sensitivity of 57.3% and a specificity of 92.1%, whereas MRI had a sensitivity of 89.2% and a specificity of 92.6%. The sensitivity of FOI increased with the degree of synovitis to 65.0% for moderate and severe synovitis (specificity 88.1%) and 76,3% for severe synovitis (specificity 80.5%). The performance of FOI decreased with the degree of synovitis with false negative results predominantly for mild (156/343, 45.5%) and moderate (160/343, 46.6%) synovitis and false positive FOI evaluations predominantly based on weak (grade 1) signals (133/163, 81,6%). CONCLUSION: FOI has a lower sensitivity than 3T-MRI in the detection of synovitis of the hand and finger joints. The diagnostic performance of FOI decreases with the degree of synovitis and with the strength of FOI signals.

Detection of intramyocardially injected DiR-labeled mesenchymal stem cells by optical and optoacoustic tomography.

The distribution of intramyocardially injected rabbit MSCs, labeled with the near-infrared dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbo-cyanine-iodide (DiR) using hybrid Fluorescence Molecular Tomography-X-ray Computed Tomography (FMT-XCT) and Multispectral Optoacoustic Tomography (MSOT) imaging technologies, was investigated. Viability and induction of apoptosis of DiR labeled MSCs were assessed by XTT- and Caspase-3/-7-testing in vitro. 2 × 106, 2 × 105 and 2 × 104 MSCs labeled with 5 and 10 µg DiR/ml were injected into fresh frozen rabbit hearts. FMT-XCT, MSOT and fluorescence cryosection imaging were performed. Concentrations up to 10 µg DiR/ml did not cause apoptosis in vitro (p > 0.05). FMT and MSOT imaging of labeled MSCs led to a strong signal. The imaging modalities highlighted a difference in cell distribution and concentration correlated to the number of injected cells. Ex-vivo cryosectioning confirmed the molecular fluorescence signal. FMT and MSOT are sensitive imaging techniques offering high-anatomic resolution in terms of detection and distribution of intramyocardially injected stem cells in a rabbit model.

[First results with a resorbable MgYREZr compression screw in unstable scaphoid fractures show extensive bone cysts]. / Erste Ergebnisse mit einer resorbierbaren MgYREZr-Kompressionsschraube bei der instabilen Kahnbeinfraktur zeigen eine massive Zystenbildung.

Osteosynthesis with headless compression screws is an established treatment option for unstable scaphoid fractures. Common implants are made of titanium alloy or steel and usually remain in place. Due to implant density and ferromagnetic properties, artefacts are common in postoperative imaging procedures, e.g. MRI. Now resorbable implants made of magnesium alloy (MgYREZr) have become available. They have biomechanical properties equivalent to human bone and may be used as an alternative to the nonresorbable screw systems.5 patients with acute scaphoid fractures were treated with a double-threaded screw made of MgYREZr. The fractures included three type A2 fractures, one type B2 fracture, and one type B3 fracture. All patients underwent clinical and radiological follow-up postoperatively, 6 weeks, 3 and 6 months and 1 year after surgery. ROM, gross grip strength and pain (VAS) were documented. The Modified Mayo Wrist Score was used. Standard X-rays of the wrist were taken preoperatively and at all follow-up visits. A CT scan was performed at least before and three months after surgery. In all X-rays malunion, resorption of the implant, implant loosening, cysts and bone healing (bridging trabecular structures) were described.All patients had a very good wrist score (95-100 points) after one year. There were no clinical complications. However, the X-rays revealed extensive resorption cysts in 3 out of the 5 patients. It was only after 6 months that the fractures were consolidated enough to allow physical work. Due to this considerable osteolysis, we did not include any further patients. Due to the observed extensive bone cysts and the long time period for bone healing, MgYREZr compression screws are currently not recommended for clinical use in scaphoid fractures. Further fundamental research is necessary.

Fluorescence molecular tomography of DiR-labeled mesenchymal stem cell implants for osteochondral defect repair in rabbit knees.

OBJECTIVES: To assess labelling efficiency of rabbit mesenchymal stem cells (MSCs) using the near-infrared dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) and detection of labelled MSCs for osteochondral defect repair in a rabbit model using fluorescence molecular tomography-X-ray computed tomography (FMT-XCT). METHODS: MSCs were isolated from New Zealand White rabbits and labelled with DiR (1.25-20 µg/mL). Viability and induction of apoptosis were assessed by XTT- and Caspase-3/-7-testing. Chondrogenic potential was evaluated by measurement of glycosaminoglycans. Labelled cells and unlabeled controls (n = 3) underwent FMT-XCT imaging before and after chondrogenic differentiation. Osteochondral defects were created surgically in rabbit knees (n = 6). Unlabeled and labelled MSCs were implanted in fibrin-clots and imaged by FMT-XCT. Statistical analyses were performed using multiple regression models. RESULTS: DiR-labelling of MSCs resulted in a dose-dependent fluorescence signal on planar images in trans-illumination mode. No significant reduction in viability or induction of apoptosis was detected at concentrations below 10 µg DiR/mL (p > .05); the chondrogenic potential of MSCs was not affected (p > .05). FMT-XCT of labelled MSCs in osteochondral defects showed a significant signal of the transplant (p < .05) with additional high-resolution anatomical information about its osteochondral integration. CONCLUSIONS: FMT-XCT allows for detection of stem cell implantation within osteochondral regeneration processes. KEY POINTS: • DiR-labelling of MSCs shows no toxic side effects or impairment of chondrogenesis. • Fluorescence molecular tomography allows for detection of MSCs for osteochondral defect repair. • FMT-XCT helps to improve evaluation of cell implantation and osteochondral regeneration processes.

Quantification of inflammatory activity in patients with Crohn's disease using diffusion weighted imaging (DWI) in MR enteroclysis and MR enterography.

Background Individual studies have demonstrated the potential of diffusion-weighted magnetic resonance imaging (DWI-MRI) for identifying inflamed bowel segments. However, these studies were conducted with rather small patient cohorts and in most cases by means of MR enterography only. Purpose To demonstrate the feasibility of detecting inflamed bowel segments in a large collective of patients with Crohn's disease using DWI in MR enteroclysis and MR enterography and to compare the results of both techniques, also considering clinical parameters by means of the Harvey-Bradshaw Index (HBI). Material and Methods Ninety-six patients underwent MRI enteroclysis and 35 patients MR enterography, both with additional DWI. The HBI as well as apparent diffusion coefficients (ADC) in areas of inflamed and normal bowel wall were determined. Thus resulting in 208 bowel segments that were visualized and subsequently statistically analyzed. Results There were no significant differences in ADC values in MR enteroclysis and MR enterography ( P = 0.383 in inflammation, P = 0.223 in normal wall). Areas of inflammation showed statistically highly significant lower ADC values than areas of normal bowel wall ( P < 0.001). An ADC threshold of 1.56 × 10-3 mm2/s can distinguish between normal and inflamed bowel segments with a sensitivity of 97.4% and a specificity of 99.2%. A highly significant correlation could be shown between ADC and HBI values ( P = 0.001). Conclusion DWI-MRI facilitates recognition of inflamed bowel segments in patients with Crohn's disease and the ADC values show an excellent correlation to the HBI. There were no significant differences in ADC values in MR enteroclysis and MR enterography. An ADC threshold of 1.56 × 10-3 mm2/s differentiates between normal and inflamed bowel wall.

Disease activity and vascular involvement in retroperitoneal fibrosis: first experience with fully integrated 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging compared to clinical and laboratory parameters.

OBJECTIVES: The aim of this study was to evaluate the value of fully integrated [18F]-FDG PET/MRI in the assessment of retroperitoneal fibrosis with regard to disease activity, extent and vascular involvement compared to clinical and laboratory parameters. METHODS: Seventeen [18F]-FDG PET/MRI examinations were performed in fourteen patients. Qualitative (visual 4-point scale) and quantitative PET parameters (maximum standardised uptake value, SUVmax; target-background ratio, TBR) as well as RF thickness and volume were correlated to clinical and inflammatory parameters and compared between therapy-naïve patients and patients under immunosuppression. Evidence for associated large-vessel vasculitis was examined. Magnetic resonance angiography (MRA) was performed to detect aneurysms or stenoses. RESULTS: Clinical parameters, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) only incompletely displayed inflammatory activity and did not correlate with PET/MRI parameters. In 29% (4/17) resp. 50% (8/16) of PET/MRI examinations active disease was detected although CRP resp. ESR were in the normal range. SUVmax, TBR and volume of the retroperitoneal mass differed significantly between therapy-naïve patients and patients under therapy (SUVmax p=0.004, TBR p=0.015, volume p=0.015), whereas thickness of the retroperitoneal mass did not (p=0.406). Large-vessel vasculitis was detected in 21% (3/14) and aortic aneurysms in 14% (2/14) of patients. Vasculitis occurred apart from the site of RF in two patients. CONCLUSIONS: Whole body hybrid [18F]-FDG-PET/MRI is superior to clinical and inflammatory parameters in disease activity assessment of RF. There may be substantial disease activity despite inflammatory parameters in the normal range. Associated large-vessel vasculitis and aneurysms may occur apart from the site of RF.

The "Intermediate" CD14++CD16+ monocyte subset increases in severe peripheral artery disease in humans.

Monocytes are key players in atherosclerotic. Human monocytes display a considerable heterogeneity and at least three subsets can be distinguished. While the role of monocyte subset heterogeneity has already been well investigated in coronary artery disease (CAD), the knowledge about monocytes and their heterogeneity in peripheral artery occlusive disease (PAOD) still is limited. Therefore, we aimed to investigate monocyte subset heterogeneity in patients with PAOD. Peripheral blood was obtained from 143 patients suffering from PAOD (Rutherford stage I to VI) and three monocyte subsets were identified by flow cytometry: CD14++CD16- classical monocytes, CD14+CD16++ non-classical monocytes and CD14++CD16+ intermediate monocytes. Additionally the expression of distinct surface markers (CD106, CD162 and myeloperoxidase MPO) was analyzed. Proportions of CD14++CD16+ intermediate monocyte levels were significantly increased in advanced stages of PAOD, while classical and non-classical monocytes displayed no such trend. Moreover, CD162 and MPO expression increased significantly in intermediate monocyte subsets in advanced disease stages. Likewise, increased CD162 and MPO expression was noted in CD14++CD16- classical monocytes. These data suggest substantial dynamics in monocyte subset distributions and phenotypes in different stages of PAOD, which can either serve as biomarkers or as potential therapeutic targets to decrease the inflammatory burden in advanced stages of atherosclerosis.

Increased intermediate CD14++CD16++ monocyte subset levels associate with restenosis after peripheral percutaneous transluminal angioplasty.

BACKGROUND AND AIMS: We aimed at studying the association of three major human monocyte subsets after percutaneous transluminal angioplasty (PTA) in patients with femoropopliteal disease. METHODS: We prospectively studied 67 sequential patients (40 male, 27 female; mean age 71 ± 11 years) treated with femoropopliteal angioplasty. Multi-color flow cytometry characterized monocyte subsets from venous blood for expression of CD14 and CD16 and intracellular myeloperoxidase (MPO) prior to, and 3, 6 and 12 months post PTA. Analyses tested associations between monocyte subsets and risk for restenosis. RESULTS: 16/67 patients (24%) developed restenosis within 12 months after PTA. Patients with hyperlipidemia had increased risk for restenosis (HR = 1.7, 95% CI 0.7-2.9, p = 0.001). Increased baseline monocytes associated with an increased risk of late restenosis (HR = 4.9, 95% CI: 1.3-18.6, p = 0.047). CD14++CD16++ 'intermediate' monocytes assessed at baseline, and after 3, 6, and 12 months significantly associated with the risk for subsequent restenosis: HR = 3.9 (95% CI: 2.4-6.5, p = 0.029), HR = 5.7 (95% CI = 0.7-44.7, p = 0.013), HR = 6.5 (95% CI: 2.5-16.9, p = 0.001) and HR = 1.5 (95% CI = 1.4-15.5 p = 0.001), respectively. Moreover, the probability for freedom of restenosis decreased with increased levels of intermediate subsets at 12 months after PTA. Additionally, intracellular MPO expression in CD14++CD16++ measured at 3, 6 and 12 months associated with an increased restenosis risk (HR = 1.5, 95% CI: 0.8-2.1, p = 0.214, HR = 1.9, 95% CI: 1.0-2.3 p = 0.051 and HR = 1.4, 95% CI: 1.0-1.8, p = 0.052). CONCLUSIONS: Our results imply altered innate immunity after angioplasty. Elevated CD14++CD16++ intermediate monocyte frequencies and increased MPO expression may identify individuals at heightened risk for restenosis.