Digitization of Follow-Up Care in Orthopedic and Trauma Surgery With Video Consultations: Health Economic Evaluation Study From a Health Provider's Perspective.

BACKGROUND: Recommendations for health care digitization as issued with the Riyadh Declaration led to an uptake in telemedicine to cope with the COVID-19 pandemic. Evaluations based on clinical data are needed to support stakeholders' decision-making on the long-term implementation of digital health. OBJECTIVE: This health economic evaluation aims to provide the first German analysis of the suitability of video consultations in the follow-up care of patients in orthopedic and trauma surgery, investigate the financial impact on hospital operations and personnel costs, and provide a basis for decisions on digitizing outpatient care. METHODS: We conducted a randomized controlled trial that evaluated video consultations versus face-to-face consultations in the follow-up care of patients in orthopedic and trauma surgery at a German university hospital. We recruited 60 patients who had previously been treated conservatively or surgically for various knee or shoulder injuries. A digital health app and a browser-based software were used to conduct video consultations. The suitability of telemedicine was assessed using the Telemedicine Satisfaction Questionnaire and the EQ-5D-5L questionnaire. Economic analyses included average time spent by physician per consultation, associated personnel costs and capacities for additional treatable patients, and the break-even point for video consultation software fees. RESULTS: After 4 withdrawals in each arm, data from a total of 52 patients (telemedicine group: n=26; control group: n=26) were used for our analyses. In the telemedicine group, 77% (20/26) of all patients agreed that telemedicine provided for their health care needs, and 69% (18/26) found telemedicine an acceptable way to receive health care services. In addition, no significant difference was found in the change of patient utility between groups after 3 months (mean 0.02, SD 0.06 vs mean 0.07, SD 0.17; P=.35). Treatment duration was significantly shorter in the intervention group (mean 8.23, SD 4.45 minutes vs mean 10.92, SD 5.58 minutes; P=.02). The use of telemedicine saved 25% (€2.14 [US $2.35]/€8.67 [US $9.53]) in personnel costs and increased the number of treatable patients by 172 annually, assuming 2 hours of video consultations per week. Sensitivity analysis for scaling up video consultations to 10% of the hospital's outpatient cases resulted in personnel cost savings of €73,056 (US $ 80,275.39) for a senior physician. A total of 23 video consultations per month were required to recoup the software fees of telemedicine through reduced personnel costs (break-even point ranging from 12-38 in the sensitivity analysis). CONCLUSIONS: Our study supports stakeholders' decision-making on the long-term implementation of digital health by demonstrating that video consultations in the follow-up care of patients in orthopedic and trauma surgery result in cost savings and productivity gains for clinics with no negative impact on patient utility. TRIAL REGISTRATION: German Clinical Trials Register DRKS00023445; https://drks.de/search/en/trial/DRKS00023445.

Quantitative assessment of angioplasty-induced vascular inflammation with 19F cardiovascular magnetic resonance imaging.

BACKGROUND: Macrophages play a pivotal role in vascular inflammation and predict cardiovascular complications. Fluorine-19 magnetic resonance imaging (19F MRI) with intravenously applied perfluorocarbon allows a background-free direct quantification of macrophage abundance in experimental vascular disease models in mice. Recently, perfluorooctyl bromide-nanoemulsion (PFOB-NE) was applied to effectively image macrophage infiltration in a pig model of myocardial infarction using clinical MRI scanners. In the present proof-of-concept approach, we aimed to non-invasively image monocyte/macrophage infiltration in response to carotid artery angioplasty in pigs using 19F MRI to assess early inflammatory response to mechanical injury. METHODS: In eight minipigs, two different types of vascular injury were conducted: a mild injury employing balloon oversize angioplasty only (BA, n = 4) and a severe injury provoked by BA in combination with endothelial denudation (BA + ECDN, n = 4). PFOB-NE was administered intravenously three days after injury followed by 1H and 19F MRI to assess vascular inflammatory burden at day six. Vascular response to mechanical injury was validated using X-ray angiography, intravascular ultrasound and immunohistology in at least 10 segments per carotid artery. RESULTS: Angioplasty was successfully induced in all eight pigs. Response to injury was characterized by positive remodeling with predominantly adventitial wall thickening and concomitant infiltration of monocytes/macrophages. No severe adverse reactions were observed following PFOB-NE administration. In vivo 19F signals were only detected in the four pigs following BA + ECDN with a robust signal-to-noise ratio (SNR) of 14.7 ± 4.8. Ex vivo analysis revealed a linear correlation of 19F SNR to local monocyte/macrophage cell density. Minimum detection limit of infiltrated monocytes/macrophages was estimated at approximately 410 cells/mm2. CONCLUSIONS: In this proof-of-concept study, 19F MRI enabled quantification of monocyte/macrophage infiltration after vascular injury with sufficient sensitivity. This may provide the opportunity to non-invasively monitor vascular inflammation with MRI in patients after angioplasty or even in atherosclerotic plaques.

[Chair of Mining Engineering and Mineral Economics-the Future]. / Bergbaukunde, quo vadis?

In order to tackle climate change and increasing competition in access to resources, the European Union has defined far-reaching transformations in the areas of energy and digitalisation as well as the conversion of the economic system towards an inclusive, circular economy in the so-called Green Deal. From a mining perspective, these transformations mean a continued growing demand for raw materials, which must be met by extracting mineral raw materials from primary deposits. However, increased quantities with "business as usual" would also increase the environmental and social impacts of mining, which is not an option, especially in Europe and Austria.Due to these facts, there is a need for research on new and improved mining methods and planning, as well as on optimised processes and machinery. This article describes how the Chair of Mining Engineering and Mineral Economics at Montanuniversität Leoben intends to use these challenges as an opportunity with its updated strategy, both for research and for teaching. For the research area, sustainability and involvement in the shaping of raw materials policy should form the framework. With a focus on digitisation and underground mining as well as strengthening the areas of open-pit mining, conveying technology and geoinformatics, research is to be future-proofed for these upcoming transformations. Teaching will continue to include a basic engineering education with specialisation in mining, whereby digitalisation will play an increasingly strong role.

Economic and Environmental Impact of Digital Health App Video Consultations in Follow-up Care for Patients in Orthopedic and Trauma Surgery in Germany: Randomized Controlled Trial.

BACKGROUND: Following the Riyadh Declaration, digital health technologies were prioritized in many countries to address the challenges of the COVID-19 pandemic. Digital health apps for telemedicine and video consultations help reduce potential disease spread in routine health care, including follow-up care in orthopedic and trauma surgery. In addition to the satisfaction, efficiency, and safety of telemedicine, its economic and environmental effects are highly relevant to decision makers, particularly for the goal of reaching carbon neutrality of health care systems. OBJECTIVE: This study aims to provide the first comprehensive health economic and environmental analysis of video consultations in follow-up care after knee and shoulder interventions in an orthopedic and trauma surgery department of a German university hospital. The analysis is conducted from a societal perspective. We analyze both economic and environmental impacts of video consultations, taking into account the goal of carbon neutrality for the German health care system by 2030. METHODS: We conducted a prospective randomized controlled trial comparing follow-up care with digital health app video consultations (intervention group) to conventional face-to-face consultations in the clinic (control group). Economic impact included the analysis of travel and time costs and production losses. Examination of the environmental impact comprised the emissions of greenhouse gases, carbon monoxide, volatile hydrocarbons, nitrogen oxides, and particulates, and the calculation of environmental costs. Sensitivity analysis included calculations with a higher cost per ton of carbon dioxide equivalent, which gives equal weight to the welfare of present and future generations. RESULTS: Data from 52 patients indicated that, from the patients' point of view, telemedicine helped reduce travel costs, time costs, and production losses, resulting in mean cost savings of €76.52 per video consultation. In addition, emissions of 11.248 kg of greenhouse gases, 0.070 kg of carbon monoxide, 0.011 kg of volatile hydrocarbons, 0.028 kg of nitrogen oxides, and 0.0004 kg of particulates could be saved per patient through avoided travel. This resulted in savings of environmental costs between €3.73 and €9.53 per patient. CONCLUSIONS: We presented the first comprehensive analysis of economic and environmental effects of telemedicine in the follow-up care of patients in orthopedic and trauma surgery in Germany. Video consultations were found to reduce the environmental footprint of follow-up care; saved travel costs, travel time, and time costs for patients; and helped to lower production losses. Our findings can support the decision-making on the use of digital health during and beyond the COVID-19 pandemic, providing decision makers with data for both economic and environmental effects. Thanks to the pragmatic design of our study, our findings can be applied to a wide range of clinical contexts and potential digital health applications that substitute outpatient hospital visits with video consultations. TRIAL REGISTRATION: German Clinical Trials Register DRKS00023445; https://tinyurl.com/4pcvhz4n.

Mortality, Risk Factors and Risk Assessment after Periprosthetic Femoral Fractures-A Retrospective Cohort Study.

Periprosthetic femoral fracture (PFF) is a devastating complication. Here, the authors aimed to determine the influence of the timing of surgery as a risk factor for mortality and poor postoperative outcome in patients suffering from PFF. A retrospective descriptive analysis of patients treated for PFF between January 2010 and March 2018 was performed. In addition to patient and treatment characteristics, we assessed mortality rates and postoperative functional outcome by using the Harris Hip and WOMAC score. One-year mortality after PFF was 10.7%. Delayed surgery after 48 h did not negatively influence mortality after PFF. The postoperative hospital stay did not influence the mortality rate, nor did it correlate with medical scores of comorbidities, general health or functionalities. Cementation of stem correlated negatively with the WOMAC score. Deceased patients had a higher Charlson Comorbidity Index (CCI) score, while American society of Anaesthesiologists (ASA) scores did not show a significant difference. There were no differences between ORIF and revision arthroplasty. In conclusion, delayed surgery after 48 h does not negatively influence mortality after PFF. The CCI seems to be a suitable tool to assess patients' risk for increased mortality after PFF, while the usually used ASA score is not able to achieve a relevant risk assessment.

Maximization of Open Hospital Capacity under Shortage of SARS-CoV-2 Vaccines-An Open Access, Stochastic Simulation Tool.

Motive. The Covid-19 pandemic has led to the novel situation that hospitals must prioritize staff for a vaccine rollout while there is acute shortage of the vaccine. In spite of the availability of guidelines from state agencies, there is partial confusion about what an optimal rollout plan is. This study investigates effects in a hospital model under different rollout schemes. Methods. A simulation model is implemented in VBA, and is studied for parameter variation in a predefined hospital setting. The implemented code is available as open access supplement. Main results. A rollout scheme assigning vaccine doses to staff primarily by staff's pathogen exposure maximizes the predicted open hospital capacity when compared to a rollout based on a purely hierarchical prioritization. The effect increases under resource scarcity and greater disease activity. Nursing staff benefits most from an exposure focused rollout. Conclusions. The model employs SARS-CoV-2 parameters; nonetheless, effects observable in the model are transferable to other infectious diseases. Necessary future prioritization plans need to consider pathogen characteristics and social factors.

Health service organisation impact on lower extremity amputations in people with type 2 diabetes with foot ulcers: systematic review and meta-analysis.

AIMS: Despite the evidence available on the epidemiology of diabetic foot ulcers and associated complications, it is not clear how specific organizational aspects of health care systems can positively affect their clinical trajectory. We aim to evaluate the impact of organizational aspects of care on lower extremity amputation rates among people with type 2 diabetes affected by foot ulcers. METHODS: We conducted a systematic review of the scientific literature published between 1999 and 2019, using the following key terms as search criteria: people with type 2 diabetes, diagnosed with diabetic foot ulcer, treated with specific processes and care pathways, and LEA as primary outcome. Overall results were reported as pooled odds ratios and 95% confidence intervals obtained using fixed and random effects models. RESULTS: A total of 57 studies were found eligible, highlighting the following arrangements: dedicated teams, care pathways and protocols, multidisciplinary teams, and combined interventions. Among them, seven studies qualified for a meta-analysis. According to the random effects model, interventions including any of the four arrangements were associated with a 29% reduced risk of any type of lower extremity amputation (OR = 0.71; 95% CI 0.52-0.96). The effect was larger when focusing on major LEAs alone, leading to a 48% risk reduction (OR = 0.52; 95% CI 0.30-0.91). CONCLUSIONS: Specific organizational arrangements including multidisciplinary teams and care pathways can prevent half of the amputations in people with diabetes and foot ulcers. Further studies using standardized criteria are needed to investigate the cost-effectiveness to facilitate wider implementation of improved organizational arrangements. Similarly, research should identify specific roadblocks to translating evidence into action. These may be structures and processes at the health system level, e.g. availability of professionals with the right skillset, reimbursement mechanisms, and clear organizational intervention implementation guidelines.

Improving the Assessment of Flow-Mediated Dilation Through Detection of Peak Time in Healthy Subjects and Subjects With Type 2 Diabetes.

The assessment of flow-mediated dilation (FMD) is widely used to quantify endothelial function. Historically, FMD was determined at 60 seconds post-cuff deflation. We investigated whether FMD would be more accurate if determined at maximum dilatory peak (MDP) than at 60 seconds in healthy subjects and subjects with type 2 diabetes mellitus (T2DM). We studied 95 healthy and 72 subjects with T2DM and assessed FMD at MDP, 60 and 90 seconds. Twenty-four healthy and 12 subjects with T2DM underwent a repeat FMD after 28 days. In healthy subjects, FMD at MDP was higher than at 60 and 90 seconds, with mean difference MDP versus 60 seconds 1.14% (95% CI: 0.6-1.7); P < .0001 and MDP versus 90 seconds 1.9% (95% CI: 1.3-2.5) with similar results in T2DM, that is, 1.0% (95% CI: 0.1-1.9) and 2.3% (95% CI: 1.3-3.2), respectively. Intraindividual variability was lowest with MDP compared with 60 and 90 seconds, that is, 15.0 versus 23.2% and 40.0%, respectively, resulting in a more than 2-fold reduction in necessary sample size. In healthy subjects and subjects with T2DM, assessment of FMD using MDP results in a more accurate and precise assessment leading to a substantial reduction in sample size.

Assessment of tissue perfusion and vascular function in mice by scanning laser Doppler perfusion imaging.

Post-occlusive reactive hyperemia (PORH) is a key feature of physiological vasomotion to appropriately match the supply/demand ratio of tissues. This adaptive mechanism is severely disturbed in endothelial dysfunction with a reduced flow-mediated dilation (FMD). Reduced PORH and FMD are powerful prognostic risk factors in cardiovascular diseases. While these parameters are frequently determined in human beings, comparable methods applicable to mouse models are sparse. We aimed to evaluate the applicability and accuracy of scanning laser Doppler perfusion imaging (LDPI) to measure PORH in the mouse hindlimb. Changes in mean perfusion in response to vasoactive drugs and PORH (assessed by scanning LDPI) were compared with changes in diameter and blood flow in the femoral artery, as assessed by high-resolution ultrasound. We found that the measured LDPI signal significantly correlated with changes of inflow into the femoral artery. Vasodilation induced by administration of nitroglycerine and acetylcholine increased vessel diameter, blood flow and mean perfusion, while vasoconstriction following administration of epinephrine decreased all three parameters. PORH was induced by temporal occlusion of the femoral artery with an external cuff. During occlusion, mean perfusion decreased to a condition of zero-perfusion and release of the cuff induced an immediate increase in blood flow that was followed by femoral artery dilation driving PORH/perfusion. Surgical removal of the femoral artery decreased mean perfusion to a zero-perfusion level and fully abolished PORH. Importantly, the measurement of the PORH response by scanning LDPI is highly reproducible as determined by repeated measurements and intra/interobserver variation analysis. Last, we found that the PORH response was dependent on nitric oxide synthase and cyclooxygenase and declined with age. Thus, we here provide novel and robust non-invasive methods to serially measure tissue perfusion at baseline and during physiological and pharmacological modulation of vasomotor tone in the hindlimb of mice. The application of these LDPI scanning and ultrasound-based methods may be useful for testing the effects of drugs affecting vasomotor function or future elucidation of mechanisms leading to vasomotor dysfunction in mice in vivo.

Computed tomography for managing periprosthetic femoral fractures. A retrospective analysis.

BACKGROUND: Periprosthetic fractures (PPF) present a common cause for revision surgery after arthroplasty. The choice of performing either an osteosynthesis or revision arthroplasty depends on the orthopedic implant anchored and loosening. Standard diagnostics include x-ray imaging. CT is usually performed to confirm implant loosening in case of ambiguous diagnosis on standard x-ray imaging. This study aimed to examine the role of CT as a diagnostic modality and its implications for treatment planning and outcome. METHODS: Patients treated for PPF from January 2010 to February 2018 were included. X-ray and CT reports were analyzed to assess implant loosening. The planning for surgery and the final surgical treatment were evaluated. In addition, patient characteristics were analyzed and compared between patients with and without additional CT as a preoperative diagnostic procedure. RESULTS: Seventy-five patients were eligible for the study. X-ray imaging was performed in 90.7% of cases. CT was performed in 60% of the cases as part of the preoperative diagnostic. A clear statement on implant stability or loosening could not be made in 69.1% after X-ray imaging and in 84.4% following CT imaging. Revision arthroplasty for loosened femoral prosthesis components was necessary in 40% of cases. No difference could be determined comparing patients with X-ray imaging to those with X-ray and additional CT. In both groups, operative treatment did not deviate from the preoperative planning. DISCUSSION: In two thirds of the conventional radiographic findings, no reliable evaluation of implant loosening was possible in femoral PPFs. Intriguingly, additional CT did not improve the evaluation of implant loosening. Nonetheless, CT scans are often performed if loosening assessment is unclear on regular radiographs. This fact can explain the bias CT results in comparison to regular radiography. However, software-supported CT diagnosis could help to adequately answer the question of loosened implants in PPF in the near future. Since the diagnosis of fracture and their morphology assessment is currently adequately performed using X-rays, CT shall not be considered as the gold standard.

Diaphyseal long bone nonunions - types, aetiology, economics, and treatment recommendations.

The intention of the current article is to review the epidemiology with related socioeconomic costs, pathophysiology, and treatment options for diaphyseal long bone delayed unions and nonunions. Diaphyseal nonunions in the tibia and in the femur are estimated to occur 4.6-8% after modern intramedullary nailing of closed fractures with an even much higher risk in open fractures. There is a high socioeconomic burden for long bone nonunions mainly driven by indirect costs, such as productivity losses due to long treatment duration. The classic classification of Weber and Cech of the 1970s is based on the underlying biological aspect of the nonunion differentiating between "vital" (hypertrophic) and "avital" (hypo-/atrophic) nonunions, and can still be considered to represent the basis for basic evaluation of nonunions. The "diamond concept" units biomechanical and biological aspects and provides the pre-requisites for successful bone healing in nonunions. For humeral diaphyseal shaft nonunions, excellent results for augmentation plating were reported. In atrophic humeral shaft nonunions, compression plating with stimulation of bone healing by bone grafting or BMPs seem to be the best option. For femoral and tibial diaphyseal shaft fractures, dynamization of the nail is an atraumatic, effective, and cheap surgical possibility to achieve bony consolidation, particularly in delayed nonunions before 24 weeks after initial surgery. In established hypertrophic nonunions in the tibia and femur, biomechanical stability should be addressed by augmentation plating or exchange nailing. Hypotrophic or atrophic nonunions require additional biological stimulation of bone healing for augmentation plating.

Absorption, Metabolism and Excretion of Cranberry (Poly)phenols in Humans: A Dose Response Study and Assessment of Inter-Individual Variability.

The beneficial health effects of cranberries have been attributed to their (poly)phenol content. Recent studies have investigated the absorption, metabolism and excretion of cranberry (poly)phenols; however, little is known about whether they follow a dose response in vivo at different levels of intake. An acute double-blind randomized controlled trial in 10 healthy men with cranberry juices containing 409, 787, 1238, 1534 and 1910 mg total (poly)phenols was performed. Blood and urine were analyzed by UPLC-Q-TOF-MS. Sixty metabolites were identified in plasma and urine including cinnamic acids, dihydrocinnamic, flavonols, benzoic acids, phenylacetic acids, benzaldehydes, valerolactones, hippuric acids, catechols, and pyrogallols. Total plasma, but not excreted urinary (poly)phenol metabolites, exhibited a linear dose response (r² = 0.74, p < 0.05), driven by caffeic acid 4-O-ß-d-glucuronide, quercetin-3-O-ß-d-glucuronide, ferulic acid 4-O-ß-d-glucuronide, 2,5-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid, ferulic acid, caffeic acid 3-O-ß-d-glucuronide, sinapic acid, ferulic acid 4-O-sulfate, 3-hydroxybenzoic acid, syringic acid, vanillic acid-4-O-sulfate, (4R)-5-(3'-hydroxyphenyl)-γ-valerolactone-4'-O-sulfate, 4-methylgallic acid-3-O-sulfate, and isoferulic acid 3-O-sulfate (all r² ≥ 0.89, p < 0.05). Inter-individual variability of the plasma metabolite concentration was broad and dependent on the metabolite. Herein, we show that specific plasma (poly)phenol metabolites are linearly related to the amount of (poly)phenols consumed in cranberry juice. The large inter-individual variation in metabolite profile may be due to variations in the gut microbiome.

Effects of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) in grade III open tibia fractures treated with unreamed nails-A clinical and health-economic analysis.

Recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) is licensed in Europe for open tibia fractures treated with unreamed nails. However, there is limited data available on the specific use of rhBMP-2 in combination with unreamed nails for open tibia fractures. The intention of the current study was to evaluate the medical and health-economic effects of rhBMP-2 in Gustilo-Anderson grade III open tibia fractures treated with unreamed nails based on individual patient data from two previously published studies. Linear regression analysis was performed on raw data of 90 patients that were either treated by standard of care with soft tissue management and unreamed nailing (SOC group) (n=50) or with rhBMP-2 in addition to soft tissue management and unreamed nailing (rhBMP-2 group) (n=40). For all types of revision, a significant lower percentage of patients (27.5%) of the rhBMP-2 group had to be revised compared to 48% of the patients of the SOC group (p=0.04). When only invasive secondary interventions such as bone grafting and nail exchange were considered, there was also a statistically significant reduction in the rhBMP-2 group with a revision rate of 10.0% (4 of 40 patients) compared to the SOC group with a revision rate of 28.0% (14 of 50 patients) (p=0.01). Mean fracture healing time of 228 days in the rhBMP-2 compared to 266 days in the SOC group was not statistically significant (p=0.24). Health-economic analysis based on a societal perspective with calculation of overall treatment costs after initial surgery and including productivity losses revealed savings of €6,239 per patient for Germany and €4,752 for the UK in favour of rhBMP-2 which was mainly driven by reduction of productivity losses. In conclusion, rhBMP-2 reduces secondary interventions in patients with grade III open tibia fractures treated with an unreamed nail and its use leads to financial savings for Germany and the UK from a societal perspective.

Medicaid expansion: considerations for states regarding newly eligible jail-involved individuals.

The expansion of Medicaid eligibility to Americans with incomes up to 138 percent of the federal poverty level should greatly increase access to coverage and services for people recently released from jail and, thus, improve health outcomes and reduce recidivism in this population. The population is disproportionately male, minority, and poor; suffers from high rates of mental and substance abuse disorders; and is expected to make up a substantial portion of the Medicaid expansion population. To ensure connections to needed services after release from jail, states could help inmates determine their eligibility and enroll in Medicaid; take advantage of federal grants to automate systems that determine eligibility; and include a robust array of behavioral health services in Medicaid benefit packages. In most states, new partnerships between Medicaid and corrections agencies at both the state and local levels will be needed to support these activities.

Assessment of the dietary intake of total flavan-3-ols, monomeric flavan-3-ols, proanthocyanidins and theaflavins in the European Union.

Dietary interventions with flavan-3-ols have shown beneficial effects on vascular function. The translation of these findings into the context of the health of the general public requires detailed information on habitual dietary intake. However, only limited data are currently available for European populations. Therefore, in the present study, we assessed the habitual intake of flavan-3-ol monomers, proanthocyanidins (PA) and theaflavins in the European Union (EU) and determined their main food sources using the EFSA (European Food Safety Authority) Comprehensive European Food Consumption Database. Data for adults aged 18-64 years were available from fourteen European countries, and intake was determined using the FLAVIOLA Flavanol Food Composition Database, developed for the present study and based on the latest US Department of Agriculture and Phenol-Explorer databases. The mean habitual intake of flavan-3-ol monomers, theaflavins and PA ranged from 181 mg/d (Czech Republic) to 793 mg/d (Ireland). The highest intakes of flavan-3-ol monomers and theaflavins were observed in Ireland (191/505 mg/d) and the lowest intakes in Spain (24/9 mg/d). In contrast, the daily intake of PA was highest in Spain (175 mg/d) and lowest in The Netherlands (96 mg/d). Main sources were tea (62%), pome fruits (11%), berries (3%) and cocoa products (3%). Tea was the major single contributor to monomer intake (75%), followed by pome fruits (6%). Pome fruits were also the main source of PA (28%). The present study provides important data on the population-based intake of flavanols in the EU and demonstrates that dietary intake amounts for flavan-3-ol monomers, PA and theaflavins vary significantly across European countries. The average habitual intake of flavan-3-ols is considerably below the amounts used in most dietary intervention studies.

Quantitative assessment of microcirculation and diffusion in the bone marrow of osteoporotic rats using VCT, DCE-MRI, DW-MRI, and histology.

BACKGROUND: Etiologic and pathophysiologic role of functional bone marrow processes is not fully understood especially in the case of osteoporosis. PURPOSE: To investigate the role of vascularization and diffusion in rat models of osteoporosis through a cross-correlation between non-invasive in-vivo imaging and invasive ex-vivo imaging of bone, bone marrow, and in particular of microcirculation. MATERIAL AND METHODS: Osteoporosis was induced in rats by combining ovariectomy (OVX) with calcium and Vitamin D3 deficiency, or with glucocorticoid (dexamethasone). For comparison, controls underwent a sham surgery. In in-vivo investigations, animals (n = 36) were examined by volumetric CT (VCT) and MRI at 1, 3, or 12 months post surgery. Using VCT, bone morphology was monitored and relative bone density r within pelvis was extracted. With DCE-MRI and DW-MRI, parameters A (amplitude), Kep (exchange rate constant), and ADC (apparent diffusion coefficient) were acquired for regions of lumbar vertebrae, pelvis, and femur. In ex-vivo investigations, selective histological sections of pelvis were either stained with hematoxylin and eosin (HE stain) for quantifying vessel size and density or immunostained for collagen IV and α-smooth muscle actin to assess vessel maturity (SMA/collagen IV ratio). RESULTS: After 12 months, decrease in DCE-MRI parameter Kep was found in all locations of osteoporotic rats (strongest in femur and lumbar vertebrae) while no significant differences were seen for parameter A and DW-MRI parameter ADC. Furthermore, vessel rarefication and maturation were observed on the histological level in animals with osteoporotic phenotype. In particular in the pelvis, the osteoporotic individuals (irrespective of the osteoporosis inducers applied) exhibited decreased Kep, significantly reduced vessel density, significantly increased vessel maturity, as well as statistically unaltered A, ADC, and vessel diameter. CONCLUSION: Changes in microcirculation but not diffusion in the bone marrow of osteoporotic rats are detected by DCE-MRI and DW-MRI due to vessel rarefication and maturation.

Calibration of cone beam CT using relative attenuation ratio for quantitative assessment of bone density: a small animal study.

PURPOSE: Cone beam computed tomography (CBCT) has the disadvantage of providing non-quantitative results for bone density determination. The aim of this study is to calibrate CBCT results by using an internal reference (such as muscle) for quantitatively assessing bone density. METHODS: We developed a new method using the relative attenuation ratio between two nearby materials (such as bone and muscle) for systemic error correction in CBCT that depends on the relative object position in the image volume. Phantom calibration was performed to calculate the acquired attenuation ratio in Hounsfield units (HU), comparable to the results from clinical multislice spiral computed tomography (MSCT). In addition, a small animal study with an osteoporotic rat model was evaluated to show the feasibility of this presented method to quantitatively assess bone density using a CBCT system. RESULTS: The phantom study results showed that the calibration process successfully corrected the systemic inaccuracy from CBCT, and the calibrated HU values agreed with the values measured from MSCT. In the small animal study, the quantitative bone densities assessed from the calibrated CBCT results were consistent with the results from MSCT data. CONCLUSION: A practical method to quantitatively estimate attenuation (HU) values for bone tissues from CBCT scans that are comparable to MSCT scans is proposed. The method may improve the quantification ability of CBCT scanning without any additional hardware requirements.

Assessment of angiogenesis in osseointegration of a silica-collagen biomaterial using 3D-nano-CT.

Bony integration of biomaterials is a complex process in which angiogenesis plays a crucial role. We evaluated micro- and nano-CT imaging to demonstrate and quantify neovascularization in bony integration of a biomaterial and to give an image based estimation for the needed resolution for imaging angiogenesis in an animal model of femora defect healing. In 8 rats 5mm full-size defects were created at the left femur that was filled with silica-collagen bone substitute material and internally fixed with plate osteosynthesis. After 6 weeks the femora were infused in situ with Microfil, harvested and scanned for micro-CT (9 µm)(3) and nano-CT (3 µm)(3) imaging. Using those 3D images, the newly formed blood vessels in the area of the biomaterial were assessed and the total vascular volume fraction, the volume of the bone substitute material and the volume of the bone defect were quantitatively characterized. Results were complemented by histology. Differences were statistically assessed using (ANOVA). High-resolution nano-CT demonstrated new blood vessel formation surrounding the biomaterial in all animals at capillary level. Immunohistochemistry confirmed the newly formed blood vessels surrounding the bone substitute material. The mean vascular volume fraction (VVF) around the implant was calculated to be 3.01 ± 0.4%. The VVF was inversely correlated with the volume of the bone substitute material (r=0.8) but not with the dimension of the fracture zone (r=0.3). Nano-CT imaging is feasible for quantitative analysis of angiogenesis during bony integration of biomaterials and a promising tool in this context for the future.

Recommending flavanols and procyanidins for cardiovascular health: current knowledge and future needs.

Data on the potential health benefits of dietary flavanols and procyanidins, especially in the context of cardiovascular health, are considerable and continue to accumulate. Significant progress has been made in flavanol analytics and the creation of phytonutrient-content food databases, and novel data emanated from epidemiological investigations as well as dietary intervention studies. However, a comprehensive understanding of the pharmacological properties of flavanols and procyanidins, including their precise mechanisms of action in vivo, and a conclusive, consensus-based accreditation of a causal relationship between intake and health benefits in the context of primary and secondary cardiovascular disease prevention is still outstanding. Thus, the objective of this review is to identify and discuss key questions and gaps that will need to be addressed in order to conclusively demonstrate whether or not dietary flavanols and procyanidins have a role in preventing, delaying the onset of, or treating cardiovascular diseases, and thus improving human life expectancy and quality of life.

Characterization of the non-invasive assessment of the cutaneous microcirculation by laser Doppler perfusion scanner.

OBJECTIVE: Microcirculatory dysfunction contributes to morbidity and mortality in vascular diseases. Here, we aimed at establishing a sensitive and valid method to measure microvascular reactivity during post-occlusive reactive hyperemia (PORH) using scanning laser Doppler perfusion imaging (LDPI) of the forearm. METHODS: In a first series, LDPI was methodologically evaluated on the volar forearm of healthy volunteers (n = 10) before and after one to five minutes of upper arm occlusion. In a second series, readings were performed in 20 healthy subjects and 20 patients with coronary artery disease (CAD). RESULTS: Three minutes of forearm occlusion were sufficient to induce maximal vasodilation during PORH as indicated by maximal increase in perfusion unit (PU) amplitude that did not further increase after five-minute occlusion. Five-minute occlusion led to a significant prolongation of PORH with greater area under curve (AUC) suggesting longer lasting vasodilation of microvessels. The five-minute occlusion was associated with lower variability as compared with three minutes (intraindividual variability: 9-17% vs. 12-21%; interindividual variability: 13-24% vs. 14-26%). CAD patients exhibited significantly reduced amplitude (105 +/- 49 vs. 164 +/- 35 PU; p < 0.001), ratio (4.7 +/- 1.8 vs. 7.1 +/- 1.8; p < 0.001), and AUC (1656 +/- 1070 vs. 2723 +/- 864 PU x minutes; p = 0.001). CONCLUSION: Scanning LDPI is a feasible and reproducible method for non-invasive assessment of the cutaneous microcirculatory response during PORH.